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This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of > 70 pg/ml.
This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of > 70 pg/ml.
"Early" septic shock is defined as a life-threatening organ dysfunction due to dysregulated host response to a proven or suspected infection which leads to a decline of Mean Arterial Pressure (MAP) < 65 mmHg, which is refractory to fluid resuscitation and requires vasopressors. Early is defined as a maximum of less than 12 hours between onset of the cardiovascular organ-dysfunction and administration of ADRECIZUMAB. Refractoriness to fluid resuscitation is defined as a lack of response to the administration of 30 mL of fluid per kilogram of body weight or is determined according to a clinician's assessment of inadequate hemodynamic results.
It is intended to enroll 300 patients from surgical, medical and mixed ICU at multiple centers in Europe.
All patients will be treated according to "International Guidelines for Management of Severe Sepsis and Septic Shock".
Eligible patients (confirmed by central verification) will be randomized (1:1:2) to ADRECIZUMAB treatment arm A (2 mg/kg) or to ADRECIZUMAB treatment arm B (4 mg/kg) or to placebo as control group. Patients assigned to the treatment arm A or B will be administered a single dose of ADRECIZUMAB as intravenous infusion over approximately 1 hour; patients assigned to the control group will be administered placebo as intravenous infusion over approximately 1 hour.
As long as the patients are on the ICU, daily measurements of clinical signs and laboratory data will be collected for safety reasons and for determination of Sequential Organ Failure Assessment Score (SOFA score). Additional blood samples for central laboratory analyses will be taken at inclusion on day 1, day 3, day 5, day 7 or day of discharge (whatever comes first) for measurement of biomarkers.
The SOFA score and its components will be determined daily for all patients over the entire stay on the ICU (28 days or until discharge whatever comes first). Safety monitoring for each patient will begin at the time of signing the Informed Consent Form and continue for 90 days after end of short-term infusion of study medication.
At selected study centers a pharmacokinetic (PK) substudy will be performed to determine the profile of ADRECIZUMAB in 80 randomized patients.
An interim analysis for efficacy is planned after 50% of patients have completed the study (n=150).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm A | Experimental | Intravenous infusion over approximately 1 hour of single i.v. dose of 2 mg/kg Adrecizumab (treatment arm A) |
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| Treatment Arm B | Experimental | Intravenous infusion over approximately 1 hour of single i.v. dose of 4 mg/kg Adrecizumab (treatment arm B) |
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| Control group | Placebo Comparator | Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab (control group) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adrecizumab | Biological | Single i.v. dose of 2 mg/kg (treatment arm A) or 4 mg/kg (treatment arm B) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) | The endpoints for the primary objective is mortality evaluated over the 90 days study period. | 90 days |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion) | The endpoints for the primary objective are to determine over the 90 days study period: Interruption of infusion due to intolerability of ADRECIZUMAB | 90 days |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs) | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group. | 90 days |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with mild severity treatment emergent events. | 90 days |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with moderate severity treatment emergent events. | 90 days |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy to be Determined by Sepsis Support Index (SSI) | The primary efficacy endpoint of this study is the Sepsis Support Index (SSI) defined as: days with organ support or dead within 14 day follow up More precisely: In the time frame of 14 day follow-up, each day on support with vasopressor, and/or mechanical ventilation, and/or renal dysfunction (defined as renal SOFA = 4), or not alive, is counted as 1. The sum over the follow up period is defined as SSI. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. |
| Measure | Description | Time Frame |
|---|---|---|
| In Sub-study Key Pharmacokinetic Parameters Peak Plasma Concentrations (Cmax) Are to be Determined in 80 Patients | peak plasma concentrations (Cmax). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | 28 days |
| In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jens Zimmermann, Dr. | Adrenomed AG | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinique Universitaire Saint-Luc (UCL Bruxelles) | Brussels | 1200 | Belgium | |||
| Antwerp University Hospital (UZA), Critical Care Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34605947 | Derived | Laterre PF, Pickkers P, Marx G, Wittebole X, Meziani F, Dugernier T, Huberlant V, Schuerholz T, Francois B, Lascarrou JB, Beishuizen A, Oueslati H, Contou D, Hoiting O, Lacherade JC, Chousterman B, Pottecher J, Bauer M, Godet T, Karakas M, Helms J, Bergmann A, Zimmermann J, Richter K, Hartmann O, Pars M, Mebazaa A; AdrenOSS-2 study participants. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med. 2021 Nov;47(11):1284-1294. doi: 10.1007/s00134-021-06537-5. Epub 2021 Oct 4. | |
| 30782906 |
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First patient enrolled: 08-Dec-2017 Last patient completed: 20-Dec-2019 Total study duration: 25 months
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Arm A | Intravenous infusion over approximately 1 hour of single i.v. dose of 2 mg/kg Adrecizumab Adrecizumab: Single i.v. dose of 2 mg/kg |
| FG001 | Treatment Arm B | Intravenous infusion over approximately 1 hour of single i.v. dose of 4 mg/kg Adrecizumab Adrecizumab: Single i.v. dose of 4 mg/kg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 28, 2019 | Dec 17, 2020 |
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Double Blind, Placebo-Controlled, Randomized, Multicenter Proof of Concept and Dose-Finding Phase II Clinical Trial
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| Placebo | Biological | Single i.v. dose of placebo (control group) |
|
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with severe severity treatment emergent events. |
| 90 days |
| 14 days |
| Sepsis Support Index (SSI) | Sepsis Support Index (SSI) at 28 day follow-up Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. | 28 days |
| Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up | Penalized Sepsis Support Index (pSSI) at day 14, defined similar to the SSI with the exception that patients that die get penalized by assigning the maximum value, i.e. the pSSI is set to 14 or 28, respectively. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. | day 14 |
| Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Persistent organ dysfunction or death at 14 and 28 day follow-up. Count of participants with either persistent organ dysfunction or death at Day 14 and Day 28. Persistent Organ Dysfunction is defined as the persistence of organ dysfunction requiring supportive technologies during the convalescent phase of critical illness and it is present when a patient has an ongoing requirement for vasopressors, dialysis, or mechanical ventilation at the outcome assessments time points, as defined by Heyland et al.; Persistent organ dysfunction plus death: a novel,composite outcome measure for critical care trials. Critical Care 2011, 15. | day 14 and day 28 |
| Mortality Rate | Day 28 mortality rate | day 28 |
| SSI and pSSI Excluding the Renal Component | Sepsis Support Index (SSI) and penalized Sepsis Support Index (pSSI) excluding the renal component. pSSI is a version of the SSI where mortality is given extra weight: Patients being alive during the 14 days' follow up will have an SSI ranging up to 14, while patients who died within that period will be assigned a score of "14 plus the number of days not being alive". Thus the SSI and pSSI score may range between zero and 28. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data. | day 14 and day 28 |
| SSI Weighted for Mortality | Sepsis Support Index (SSI) Weighted for Mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. | day 14 |
| Individual Sepsis Support Index Components | Individual Sepsis Support Index (SSI) components (hemodynamic, respiratory and renal failure) with and without mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data. | day 14 and day 28 |
| Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | Sequential Organ Failure Assessment (SOFA) Score: SOFA score change at Day 3 - baseline, delta = difference between maximum and minimum score during ICU stay, mean/maximum/total daily score during ICU stay, SOFA-3 (score limited to cardiovascular, respiratory and renal function). Measured at baseline and Day 3. SOFA score: Minimum possible score is 0, maximum is 24. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28. SOFA-3 score: Minimum possible score is 0, maximum is 12. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28. | 28 days |
| Change in Renal Function (Creatinine) | Change in renal function as change in creatinine (day 3 - day 1, day 7 - day 1) | day 1, day 3 and day 7 |
| Duration of Stay at ICU/ Hospital | Duration of stay at ICU / hospital. The number of participants analyzed differs per row due to missing data. | 90 days |
| Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Changes of Mean Arterial Pressure (MAP). Change from baseline to day 28/last day in ICU was calculated (value at day 28 or last collected value minus value at baseline). MAP was collected at screening and daily from day 1 to day 28 or discharge as well as on the follow-up visit day 28. Vital signs were assessed as min/max values within 24 hours except at screening and on the follow-up visit day 28. | 28 days |
| Changes of Functional Parameter Creatinine During Stay at ICU | Changes of creatinine. Measurement for baseline and Day 28 given. Creatinine was measured in the daily blood sample during ICU stay until discharge or Day 28 in a local laboratory assessment. | 28 days |
| Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU | Changes of Partial Pressure of Oxygen in Arterial Blood (PaO2) / Fraction of inspired oxygen (FiO2) from baseline to the last observed value are measured. PaO2 and FiO2 was collected if an arterial line was in place. The arterial blood was assessed for PaO2 and FiO2. Both were measured in mmHg. | 28 days |
| Changes of Functional Parameter Blood Lactate During Stay at ICU | Changes of blood lactate from baseline to Day 28 or discharge. Blood lactate was measured in the daily blood sample from baseline to ICU discharge or until Day 28. | 28 days |
| Changes of Functional Parameter Fluid Balance During Stay at ICU | Changes of fluid balance - Last Observed Value. Percentage of Participants with low (</=1000 mL) and high (>1000 mL) Fluid balance at the last observed value. Daily fluid intake will be calculated as the sum of all intravenous and oral fluids. The daily fluid output will be calculated as the sum of the volume of urine output, ultrafiltration fluid, drain fluid, and estimated gastrointestinal losses (including stools only in the presence of profound diarrhea). Insensitive losses will not be taken into account because they are difficult to assess reliably. Daily fluid balance (according to baseline patient weight) will be calculated by subtracting the total fluid output from the total intake. | 28 days |
| Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU | Changes of Mid-Regional pro-Adrenomedullin (MR-proADM) between baseline and last observed value. MR-proADM was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | 28 days |
| Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU | Changes of inflammatory marker Procalcitonine (PCT) between baseline and last observed value. PCT was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | 28 days |
| Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU | Changes of inflammatory marker Interleukin-6 (IL-6) between baseline and last observed value. IL-6 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | 28 days |
| Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU | Changes of dipeptidyl peptidase 3 (DPP3) between baseline and last observed value. DPP3 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | 28 days |
| Vasopressor Use (Drug, Highest Dose) | Vasopressor use (drug, highest dose). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first). | 28 days |
| Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Patient reported outcomes: Quality of Life Form by EuroQoL Group, version "Euro-QoL-5" (day 28 and day 90). Change 1 = Visual analog scale (VAS) at discharge - VAS at day 90. Change 2 = VAS at day 28 - VAS at day 90. Minimum value on the scale is 0, maximum value on the scale is 100. A lower score indicates a worse outcome. As the change between two scores is calculated, a negative number indicates a worsening. | day 28 and day 90 |
| Vital Signs | Vital signs: heart rate (beat per minute) Change from baseline to Day 7. | 7 days |
| Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up | Penalized Sepsis Support Index (pSSI) at 28 day follow-up, is a version of the SSI where mortality is given extra weight: Patients being alive duringthe 14 days' follow up will have an SSI ranging up to 14 (as defined above), while patients who died within that period will be assigned a score of "14 plus the number of days not being alive". Thus the weighted SSI score may range between zero and 28. A higher score means a worse outcome. | day 28 |
| Vasopressor Use (Drug, Duration) | Vasopressor use (drug, duration). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first). | 28 days |
| Change in Renal Function (penKid) | Change in renal function as change in penKid (day 3 - day 1, day 7 - day 1). penKid was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | day 1, day 3 and day 7 |
| Vital Signs - Blood Pressure | Vital signs: blood pressure - mean arterial pressure (MAP) mmHg Change from baseline to Day 7. | 7 days |
Time to Cmax (tmax) in hours (h) |
| 28 days |
| In Sub-study Key Pharmacokinetic Parameter AUC is to be Determined in 80 Patients | systemic exposure : Area under the plasma concentration versus time curve (AUC). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | 28 days |
| In Sub-study Key Pharmacokinetic Parameter Volume of Distribution is to be Determined in 80 Patients | volume of distribution (V). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | 28 days |
| In Sub-study Key Pharmacokinetic Parameter Systemic Clearance is to be Determined in 80 Patients | systemic clearance (CL). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | 28 days |
| In Sub-study Key Pharmacokinetic Parameter Elimination Half-life is to be Determined in 80 Patients | elimination half-life (t½). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | 28 days |
| Edegem |
| 2650 |
| Belgium |
| Groupe Jolimont, Hospitalier de Jolimont | Haine-Saint-Paul | 7100 | Belgium |
| Clinique St. Pierre, Intensive Care | Ottignies | 1340 | Belgium |
| Medical Intensive Care Medicine, Centre hospital - universitaire | Angers | Cedex | 49933 | France |
| CH Victor Dupouy | Argenteuil | Cedex | 95107 | France |
| Hopital Beaujon; Anesthesie Reanimation | Clichy | Cedex | 92118 | France |
| CHU de Limoges | Limoges | Cedex | 87042 | France |
| CHU de Nantes; Medicine Intensive Reanimation | Nantes | Cedex | 44093 | France |
| CHRU Bretonneau, Medecine Intensive Réanimation | Tours | Cedex | 37044 | France |
| University Hospital of Clermont-Ferrand, Dept. of Perioperative Medicine | Clermont-Ferrand | 63003 | France |
| AP-HP, Hopital Louis Mourier, Réanimation Médicale | Colombes | 92700 | France |
| CHD-Vendée | La Roche-sur-Yon | 85000 | France |
| Hôpital de Bicêtre, Service d'anesthésie-réanimation chirurgicale | Le Kremlin-Bicêtre | 94270 | France |
| Hôpital Lariboisière, Dept. d'Anesthesie | Paris | 75010 | France |
| Hôpital Lariboisière, Réanimation Médicale et Traumatologique | Paris | 75010 | France |
| Hôpital Saint-Louis, Service d'Anesthésie-Réanimation | Paris | 75010 | France |
| Hôpital Européen Georges Pompidou, Service d'Anesthésie-Réanimation Chirurgicale, Université Paris Descartes | Paris | 75015 | France |
| Nouvel Hopital Civil | Strasbourg | 67091 | France |
| Hôpital de Hautepierre , Hôpitaux Universitaires de Strasbourg, Unité de Réanimation Chirurgicale, Service d'Anesthésie-Réanimation Chirurgicale | Strasbourg | 67200 | France |
| Universitätsklinikum Aachen, Klinik für Operative Intensivmedizin | Aachen | 52074 | Germany |
| Universitätsklinikum Hamburg-Eppendorf Klinik für Intensivmedizin | Hamburg | 20246 | Germany |
| Universitätsklinikum Jena Klinik für Anästhesiologie und Intensivmedizin | Jena | 07747 | Germany |
| Universitätsklinikum Münster Klinik für Anästhesiologie, operative Intensivmedizin und Schmerztherapie | Münster | 48149 | Germany |
| Universitätsmedizin Rostock Klinik und Poliklinik für Anästhesiologie und Intensivtherapie | Rostock | 18057 | Germany |
| Gelderse Vallei Hospital, Department of Intensive Care | Ede | 6716 RP | Netherlands |
| Medisch Spectrum Twente, Department of Intensive Care | Enschede | 7512 KZ | Netherlands |
| Zuyderland Medical Center, Department of Intensive Care | Heerlen | 6401 CX | Netherlands |
| Radboud UMC Intensive Care | Nijmegen | 6525 GA | Netherlands |
| Canisius-Wilhelmina-Ziekenhuis (CWZ), Intensive Care | Nijmegen | 6532 SZ | Netherlands |
| Derived |
| Geven C, Blet A, Kox M, Hartmann O, Scigalla P, Zimmermann J, Marx G, Laterre PF, Mebazaa A, Pickkers P. A double-blind, placebo-controlled, randomised, multicentre, proof-of-concept and dose-finding phase II clinical trial to investigate the safety, tolerability and efficacy of adrecizumab in patients with septic shock and elevated adrenomedullin concentration (AdrenOSS-2). BMJ Open. 2019 Feb 19;9(2):e024475. doi: 10.1136/bmjopen-2018-024475. |
| FG002 | Control Group | Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Arm A | Intravenous infusion over approximately 1 hour of single i.v. dose of 2 mg/kg Adrecizumab Adrecizumab: Single i.v. dose of 2 mg/kg |
| BG001 | Treatment Arm B | Intravenous infusion over approximately 1 hour of single i.v. dose of 4 mg/kg Adrecizumab Adrecizumab: Single i.v. dose of 4 mg/kg |
| BG002 | Control Group | Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Location before ICU admission | Number | participants |
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| Origin of sepsis | Number | participants |
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| Body Mass Index (BMI) | Treatment group A Row population differs from the Overall because height was not determined for one subject, therefore, no BMI was calculated. Treatment group C Row population differs from the Overall because height was not determined for one subject, therefore, no BMI was calculated. | Mean | Full Range | kg/m^2 |
| |||||||||
| Body temperature | Treatment group A Row population differs from the Overall because body temperature was not done for 6 subjects. Treatment group B Row population differs from the Overall because body temperature was not done for 4 subjects. Treatment group C Row population differs from the Overall because body temperature was not done for 7 subjects. | Mean | Full Range | degrees C |
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| Heart rate | Mean | Full Range | bpm |
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| Mean arterial pressure | Mean | Full Range | mmHg |
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| Respiratory rate | Treatment group A Row population differs from the Overall because respiratory rate was not done for 2 subjects Treatment group C Row population differs from the Overall because respiratory rate was not done for 3 subjects | Mean | Full Range | breaths/min |
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| Bio-ADM | bio-ADM measures the plasma level of the biological active Adrenomedullin, a vasoactive hormone that regulates blood pressure and vascular integrity Note results characterized as "3000" are to be read as >3000 | Mean | Full Range | pg/mL (local) |
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| Blood lactate | Treatment group A Row population differs from the Overall because blood lactate was not done for 4 subjects Treatment group B Row population differs from the Overall because blood lactate was not done for 2 subjects Treatment group C Row population differs from the Overall because blood lactate was not done for 3 subjects | Mean | Full Range | mmol/L |
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| Creatinine | Treatment group A Row population differs from the Overall because creatinine was not done for 1 subject Treatment group B Row population differs from the Overall because creatinine was not done for 1 subject | Mean | Full Range | μmol/L |
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| Apache II Score | Minimum score = 0; maximum score = 71. Increasing score is associated with increasing risk of hospital death. | Treatment group A Row population differs from the Overall because Apache II Score was not done for 10 subjects Treatment group B Row population differs from the Overall because Apache II Score was not done for 11 subjects Treatment group C Row population differs from the Overall because Apache II Score was not done for 8 subjects | Mean | Full Range | units on a scale |
| ||||||||
| Sequential Organ Failure Assessment (SOFA) Score | The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems. SOFA score: Minimum possible score is 0, maximum is 24. A higher score meas a worse outcome. | Treatment group A Row population differs from the Overall because SOFA Score was not done for 11 subjects Treatment group B Row population differs from the Overall because SOFA Score was not done for 16 subjects Treatment group C Row population differs from the Overall because SOFA Score was not done for 20 subjects | Mean | Full Range | units on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) | The endpoints for the primary objective is mortality evaluated over the 90 days study period. | Full Analysis Set | Posted | Mean | Standard Error | days | 90 days |
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| Primary | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion) | The endpoints for the primary objective are to determine over the 90 days study period: Interruption of infusion due to intolerability of ADRECIZUMAB | Safety Analysis Set | Posted | Number | Interruptions | 90 days |
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| Primary | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs) | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group. | Safety Analysis Set | Posted | Count of Participants | Participants | 90 days |
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| Primary | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with mild severity treatment emergent events. | Safety Analysis Set | Posted | Count of Participants | Participants | 90 days |
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| Primary | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with moderate severity treatment emergent events. | Safety Analysis Set | Posted | Count of Participants | Participants | 90 days |
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| Primary | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with severe severity treatment emergent events. | Safety Analysis Set | Posted | Count of Participants | Participants | 90 days |
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| Secondary | Efficacy to be Determined by Sepsis Support Index (SSI) | The primary efficacy endpoint of this study is the Sepsis Support Index (SSI) defined as: days with organ support or dead within 14 day follow up More precisely: In the time frame of 14 day follow-up, each day on support with vasopressor, and/or mechanical ventilation, and/or renal dysfunction (defined as renal SOFA = 4), or not alive, is counted as 1. The sum over the follow up period is defined as SSI. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | 14 days |
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| Secondary | Sepsis Support Index (SSI) | Sepsis Support Index (SSI) at 28 day follow-up Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | 28 days |
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| Secondary | Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up | Penalized Sepsis Support Index (pSSI) at day 14, defined similar to the SSI with the exception that patients that die get penalized by assigning the maximum value, i.e. the pSSI is set to 14 or 28, respectively. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | day 14 |
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| Secondary | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Persistent organ dysfunction or death at 14 and 28 day follow-up. Count of participants with either persistent organ dysfunction or death at Day 14 and Day 28. Persistent Organ Dysfunction is defined as the persistence of organ dysfunction requiring supportive technologies during the convalescent phase of critical illness and it is present when a patient has an ongoing requirement for vasopressors, dialysis, or mechanical ventilation at the outcome assessments time points, as defined by Heyland et al.; Persistent organ dysfunction plus death: a novel,composite outcome measure for critical care trials. Critical Care 2011, 15. | Full Analysis Set | Posted | Count of Participants | Participants | day 14 and day 28 |
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| Secondary | Mortality Rate | Day 28 mortality rate | Full Analysis Set | Posted | Mean | Standard Error | days | day 28 |
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| Secondary | SSI and pSSI Excluding the Renal Component | Sepsis Support Index (SSI) and penalized Sepsis Support Index (pSSI) excluding the renal component. pSSI is a version of the SSI where mortality is given extra weight: Patients being alive during the 14 days' follow up will have an SSI ranging up to 14, while patients who died within that period will be assigned a score of "14 plus the number of days not being alive". Thus the SSI and pSSI score may range between zero and 28. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | day 14 and day 28 |
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| Secondary | SSI Weighted for Mortality | Sepsis Support Index (SSI) Weighted for Mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | day 14 |
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| Secondary | Individual Sepsis Support Index Components | Individual Sepsis Support Index (SSI) components (hemodynamic, respiratory and renal failure) with and without mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | day 14 and day 28 |
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| Secondary | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | Sequential Organ Failure Assessment (SOFA) Score: SOFA score change at Day 3 - baseline, delta = difference between maximum and minimum score during ICU stay, mean/maximum/total daily score during ICU stay, SOFA-3 (score limited to cardiovascular, respiratory and renal function). Measured at baseline and Day 3. SOFA score: Minimum possible score is 0, maximum is 24. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28. SOFA-3 score: Minimum possible score is 0, maximum is 12. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | 28 days |
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| Secondary | Change in Renal Function (Creatinine) | Change in renal function as change in creatinine (day 3 - day 1, day 7 - day 1) | Full Analysis Set | Posted | Mean | Standard Deviation | μmol/L | day 1, day 3 and day 7 |
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| Secondary | Duration of Stay at ICU/ Hospital | Duration of stay at ICU / hospital. The number of participants analyzed differs per row due to missing data. | Full Analysis Set | Posted | Mean | Standard Deviation | days | 90 days |
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| Secondary | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Changes of Mean Arterial Pressure (MAP). Change from baseline to day 28/last day in ICU was calculated (value at day 28 or last collected value minus value at baseline). MAP was collected at screening and daily from day 1 to day 28 or discharge as well as on the follow-up visit day 28. Vital signs were assessed as min/max values within 24 hours except at screening and on the follow-up visit day 28. | Full Analysis Set | Posted | Mean | Standard Deviation | mmHg | 28 days |
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| Secondary | Changes of Functional Parameter Creatinine During Stay at ICU | Changes of creatinine. Measurement for baseline and Day 28 given. Creatinine was measured in the daily blood sample during ICU stay until discharge or Day 28 in a local laboratory assessment. | Full Analysis Set | Posted | Mean | Standard Deviation | μmol/L | 28 days |
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| Secondary | Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU | Changes of Partial Pressure of Oxygen in Arterial Blood (PaO2) / Fraction of inspired oxygen (FiO2) from baseline to the last observed value are measured. PaO2 and FiO2 was collected if an arterial line was in place. The arterial blood was assessed for PaO2 and FiO2. Both were measured in mmHg. | Full Analysis Set | Posted | Mean | Standard Deviation | ratio | 28 days |
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| Secondary | Changes of Functional Parameter Blood Lactate During Stay at ICU | Changes of blood lactate from baseline to Day 28 or discharge. Blood lactate was measured in the daily blood sample from baseline to ICU discharge or until Day 28. | Full Analysis Set | Posted | Mean | Standard Deviation | mmol/L | 28 days |
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| Secondary | Changes of Functional Parameter Fluid Balance During Stay at ICU | Changes of fluid balance - Last Observed Value. Percentage of Participants with low (</=1000 mL) and high (>1000 mL) Fluid balance at the last observed value. Daily fluid intake will be calculated as the sum of all intravenous and oral fluids. The daily fluid output will be calculated as the sum of the volume of urine output, ultrafiltration fluid, drain fluid, and estimated gastrointestinal losses (including stools only in the presence of profound diarrhea). Insensitive losses will not be taken into account because they are difficult to assess reliably. Daily fluid balance (according to baseline patient weight) will be calculated by subtracting the total fluid output from the total intake. | Full Analysis Set | Posted | Number | percentage of participants | 28 days |
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| Secondary | Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU | Changes of Mid-Regional pro-Adrenomedullin (MR-proADM) between baseline and last observed value. MR-proADM was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | Full Analysis Set | Posted | Mean | Standard Deviation | mmol/L | 28 days |
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| Secondary | Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU | Changes of inflammatory marker Procalcitonine (PCT) between baseline and last observed value. PCT was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | Full Analysis Set | Posted | Mean | Standard Deviation | ng/mL | 28 days |
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| Secondary | Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU | Changes of inflammatory marker Interleukin-6 (IL-6) between baseline and last observed value. IL-6 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | Full Analysis Set | Posted | Mean | Standard Deviation | pg/mL | 28 days |
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| Secondary | Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU | Changes of dipeptidyl peptidase 3 (DPP3) between baseline and last observed value. DPP3 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | Full Analysis Set | Posted | Mean | Standard Deviation | ng/mL | 28 days |
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| Secondary | Vasopressor Use (Drug, Highest Dose) | Vasopressor use (drug, highest dose). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first). | Full Analysis Set | Posted | Mean | Standard Deviation | μg/kg/min | 28 days |
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| Secondary | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Patient reported outcomes: Quality of Life Form by EuroQoL Group, version "Euro-QoL-5" (day 28 and day 90). Change 1 = Visual analog scale (VAS) at discharge - VAS at day 90. Change 2 = VAS at day 28 - VAS at day 90. Minimum value on the scale is 0, maximum value on the scale is 100. A lower score indicates a worse outcome. As the change between two scores is calculated, a negative number indicates a worsening. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | day 28 and day 90 |
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| Secondary | Vital Signs | Vital signs: heart rate (beat per minute) Change from baseline to Day 7. | Full Analysis Set | Posted | Mean | Standard Deviation | beats per minute | 7 days |
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| Secondary | Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up | Penalized Sepsis Support Index (pSSI) at 28 day follow-up, is a version of the SSI where mortality is given extra weight: Patients being alive duringthe 14 days' follow up will have an SSI ranging up to 14 (as defined above), while patients who died within that period will be assigned a score of "14 plus the number of days not being alive". Thus the weighted SSI score may range between zero and 28. A higher score means a worse outcome. | Full Analysis Set | Posted | Mean | Standard Deviation | score on a scale | day 28 |
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| Secondary | Vasopressor Use (Drug, Duration) | Vasopressor use (drug, duration). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first). | Full Analysis Set | Posted | Mean | Standard Deviation | days | 28 days |
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| Secondary | Change in Renal Function (penKid) | Change in renal function as change in penKid (day 3 - day 1, day 7 - day 1). penKid was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). | Full Analysis Set | Posted | Mean | Standard Deviation | pmol/L | day 1, day 3 and day 7 |
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| Secondary | Vital Signs - Blood Pressure | Vital signs: blood pressure - mean arterial pressure (MAP) mmHg Change from baseline to Day 7. | Full Analysis Set | Posted | Mean | Standard Deviation | mmHg | 7 days |
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| Other Pre-specified | In Sub-study Key Pharmacokinetic Parameters Peak Plasma Concentrations (Cmax) Are to be Determined in 80 Patients | peak plasma concentrations (Cmax). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | Pharmacokinetic Analysis Set | Posted | Mean | Standard Deviation | μg/mL | 28 days |
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| Other Pre-specified | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | Time to Cmax (tmax) in hours (h) | Pharmacokinetic Analysis Set | Posted | Count of Participants | Participants | 28 days |
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| Other Pre-specified | In Sub-study Key Pharmacokinetic Parameter AUC is to be Determined in 80 Patients | systemic exposure : Area under the plasma concentration versus time curve (AUC). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | Pharmacokinetic Analysis Set | Posted | Mean | Standard Deviation | h*μg/mL | 28 days |
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| Other Pre-specified | In Sub-study Key Pharmacokinetic Parameter Volume of Distribution is to be Determined in 80 Patients | volume of distribution (V). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | Pharmacokinetic Analysis Set | Posted | Mean | Standard Deviation | L | 28 days |
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| Other Pre-specified | In Sub-study Key Pharmacokinetic Parameter Systemic Clearance is to be Determined in 80 Patients | systemic clearance (CL). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | Pharmacokinetic Analysis Set | Posted | Mean | Standard Deviation | L/h | 28 days |
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| Other Pre-specified | In Sub-study Key Pharmacokinetic Parameter Elimination Half-life is to be Determined in 80 Patients | elimination half-life (t½). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. | Pharmacokinetic Analysis Set | Posted | Mean | Standard Deviation | h | 28 days |
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All Adverse Events whether serious or non-serious and judged related or unrelated to the study drug occurring during the study period (Day 1 (inclusion and single IMP administration) until 90 days after study drug administration (=Day1)) were collected. The study period was 2 years.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Arm A | Intravenous infusion over approximately 1 hour of single i.v. dose of 2 mg/kg Adrecizumab Adrecizumab: Single i.v. dose of 2 mg/kg | 26 | 72 | 46 | 72 | 44 | 72 |
| EG001 | Treatment Arm B | Intravenous infusion over approximately 1 hour of single i.v. dose of 4 mg/kg Adrecizumab Adrecizumab: Single i.v. dose of 4 mg/kg | 24 | 77 | 42 | 77 | 68 | 77 |
| EG002 | Control Group | Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo | 54 | 152 | 96 | 152 | 84 | 152 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Septic shock | Infections and infestations | MedDRA (22.1) | Non-systematic Assessment |
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| Arteriovenous fistula | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
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| Arterial haemorrhage | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
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| Acute hepatic failure | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | MedDRA (22.1) | Systematic Assessment |
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| Infectious pleural effusion | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Necrotising fasciitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
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| Intra-abdominal haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
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| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
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| Hepatic failure | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
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| Shock haemorrhagic | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
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| Fistula of small intestine | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
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| Lung abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
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| Clostridium colitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
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| Cholangiocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
| |
| Electrocardiogram repolarisation abnormality | Investigations | MedDRA (22.1) | Systematic Assessment |
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| Overdose | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
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| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Conduction disorder | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
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| Catheter site haemorrhage | General disorders | MedDRA (22.1) | Systematic Assessment |
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| Intensive care unit acquired weakness | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Bronchial haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Death | General disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Enterococcal sepsis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Urinary tract infection enterococcal | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Intestinal ischaemia | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Hyperlactacidaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Acinetobacter bacteraemia | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
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| Status epilepticus | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Gangrene | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
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| Shock | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
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| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
| |
| Abdominal wound dehiscence | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
| |
| Gastrointestinal perforation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Blood lactic acid increased | Investigations | MedDRA (22.1) | Systematic Assessment |
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| Duodenal perforation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
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| Heart valve incompetence | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
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| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
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| Gastric ulcer | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
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| Weaning failure | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
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| Ileus paralytic | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Intestinal anastomosis complication | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Embedded device | Product Issues | MedDRA (22.1) | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Herpes simplex pneumonia | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Herpes sepsis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
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| Large intestine perforation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Multimorbidity | General disorders | MedDRA (22.1) | Systematic Assessment |
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| Withdrawal of life support | Surgical and medical procedures | MedDRA (22.1) | Systematic Assessment |
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| Critical illness | General disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (22.1) | Systematic Assessment |
| |
| Endotracheal intubation complication | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Respiratory fatigue | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Stress cardiomyopathy | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Escherichia peritonitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Peripheral artery occlusion | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Osmotic demyelination syndrome | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Psoas abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Intervertebral discitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pharyngeal haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Subdiaphragmatic abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Atrioventricular block second degree | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Mechanical ileus | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Intra-abdominal fluid collection | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Impaired healing | General disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Myocarditis septic | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Splenic necrosis | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
| |
| Abdominal abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Subileus | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Ventricular hypokinesia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Eschar | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
| |
| Coagulopathy | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Gastroduodenal haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Abdominal wall haematoma | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Vascular pseudoaneurysm | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Gastrointestinal stoma complication | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
| |
| Wound abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Hepatic necrosis | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Respiratory acidosis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pelvic abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Peritoneal haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Primary adrenal insufficiency | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Oesophageal adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
| |
| Renal haematoma | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Venous thrombosis limb | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Pulmonary sepsis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Oedema blister | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Skin necrosis | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
| |
| Myocarditis | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jens Zimmermann | Adrenomed AG | +49 (0) 3302 20 77 810 | jzimmermann@adrenomed.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 5, 2020 | Dec 17, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
Not provided
Not provided
| ID | Term |
|---|---|
| C000706631 | enibarcimab |
Not provided
Not provided
Not provided
|
|
|
| Black |
|
|
| Caucasian |
|
|
| Other |
|
|
| Not reported |
|
|
|
| Belgium |
|
|
| France |
|
|
| Germany |
|
|
|
| Hospital |
|
|
|
| Lung |
|
|
| Urinary tract |
|
|
| Skin and soft tissue |
|
|
| Bile duct infection |
|
|
| Blood stream |
|
|
| Central nervous system |
|
|
| Catheter |
|
|
| Other |
|
|
|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
|
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| OG003 | Control Group | Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
| Participants |
|
|
| Control Group |
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| OG003 | Control Group | Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab
Placebo: Single i.v. dose of placebo
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
Treatment Arm A and Treatment Arm B combined
| OG003 | Control Group | Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab
Placebo: Single i.v. dose of placebo
|
|
| Units | Counts |
|---|
| Participants |
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab Placebo: Single i.v. dose of placebo |
|
|
|
|
Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab
Placebo: Single i.v. dose of placebo
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
|
|
|
|
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|---|---|
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
|---|---|
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| Title | Measurements |
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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