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| ID | Type | Description | Link |
|---|---|---|---|
| 1U01NS088312-01 | U.S. NIH Grant/Contract | View source | |
| U01NS077352 | U.S. NIH Grant/Contract | View source | |
| U01NS077179-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
| Cedars-Sinai Medical Center | OTHER |
| Massachusetts General Hospital | OTHER |
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The purpose of this study was to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of multiple ascending intravenous doses of 3K3A-APC, a Recombinant Variant of Human activated protein C (APC), in in the treatment of acute ischemic stroke following treatment with recombinant tissue plasminogen activator (tPA), mechanical thrombectomy or both.
This was a multicenter, prospective, randomized, controlled, double-blinded Phase 2 study intended to evaluate the safety, PK and preliminary efficacy of 3K3A-APC following treatment with tPA, mechanical thrombectomy or both in subjects with moderate to severe acute ischemic stroke.
Approximately 115 subjects were to be randomized, which included the planned 88 subjects in groups of 4 subjects to either 3K3A-APC or placebo (in a 3:1 ratio) and the additional placebo subjects who were enrolled during safety review pauses. This study used a modified version of the continual reassessment method (CRM) in order to establish a maximum tolerated dose (MTD).
Eligible subjects received 3K3A-APC or placebo every 12 hours for up to 5 doses (approximately 3 days), or until discharge from the hospital, whichever occurred first. Subjects were monitored for safety evaluations through Day 7 (or discharge, if earlier) and were expected to be seen on Day 7, 14, 30, and 90 for safety and outcome evaluations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 120 µg/kg of 3K3A-APC | Active Comparator | 3K3A-APC, q12h for up to 5 doses |
|
| 240 µg/kg of 3K3A-APC | Active Comparator | 3K3A-APC, q12h for up to 5 doses |
|
| 360 µg/kg of 3K3A-APC | Active Comparator | 3K3A-APC, q12h for up to 5 doses |
|
| 540 µg/kg of 3K3A-APC | Active Comparator | 3K3A-APC, q12h for up to 5 doses |
|
| Placebo | Placebo Comparator | Matching placebo, q12h for up to 5 doses |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3K3A-APC | Biological | 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events That Meet Dose-limiting Toxicity (DLT) Criteria Specified in Protocol | Specific AEs in the study were defined in the protocol to be dose-limiting toxicity events. Any given patient was adjudicated in a binary way to either have had a DLT or not to have had a DLT. | 48-hours following last dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Presence of Measurable Bleeds in the Brain (Hemorrhage and Microbleeds) as Determined by 1.5T MRI | MRI examination to include-at minimum-T1 and T2 weighted images, as well as diffusion weighted imaging (DWI) and susceptibility weighted imaging (SWI) sequences. Post-tPA microbleeds-defined as hypointensities less than 5mm in diameter seen on SWI-will be counted as tPA-related only if found within the ischemic territory. All other areas of hypointensity on SWI larger than 5mm diameter will be counted as tPA-related regardless of the territory in which they are found. All treated subjects (regardless of dose) will be compared to all placebo subjects using a Pearson chi-square test. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick D. Lyden, MD | Cedars-Sinai Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stroke Center | Los Angeles | California | 90048 | United States | ||
| Stroke Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24372304 | Background | Lyden P, Levy H, Weymer S, Pryor K, Kramer W, Griffin JH, Davis TP, Zlokovic B. Phase 1 safety, tolerability and pharmacokinetics of 3K3A-APC in healthy adult volunteers. Curr Pharm Des. 2013;19(42):7479-85. doi: 10.2174/1381612819666131230131454. | |
| 30450637 | Derived | Lyden P, Pryor KE, Coffey CS, Cudkowicz M, Conwit R, Jadhav A, Sawyer RN Jr, Claassen J, Adeoye O, Song S, Hannon P, Rost NS, Hinduja A, Torbey M, Lee JM, Benesch C, Rippee M, Rymer M, Froehler MT, Clarke Haley E, Johnson M, Yankey J, Magee K, Qidwai J, Levy H, Mark Haacke E, Fawaz M, Davis TP, Toga AW, Griffin JH, Zlokovic BV; NeuroNEXT Clinical Trials Network NN104 Investigators. Final Results of the RHAPSODY Trial: A Multi-Center, Phase 2 Trial Using a Continual Reassessment Method to Determine the Safety and Tolerability of 3K3A-APC, A Recombinant Variant of Human Activated Protein C, in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy or both in Moderate to Severe Acute Ischemic Stroke. Ann Neurol. 2019 Jan;85(1):125-136. doi: 10.1002/ana.25383. Epub 2019 Jan 7. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 120 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| FG001 | 240 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| FG002 | 360 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| FG003 | 540 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| FG004 | Placebo | Matching placebo, q12h for up to 5 doses Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | 120 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| BG001 | 240 µg/kg of 3K3A-APC |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants With Adverse Events That Meet Dose-limiting Toxicity (DLT) Criteria Specified in Protocol | Specific AEs in the study were defined in the protocol to be dose-limiting toxicity events. Any given patient was adjudicated in a binary way to either have had a DLT or not to have had a DLT. | Evaluable participants | Posted | Count of Participants | Participants | 48-hours following last dose |
|
AEs were collected through Study Day 7 and were followed until resolution or a new baseline was established, up to Study Day 90. SAEs were collected through Study Day 30, and were followed until resolution (or resolution with sequelae), up to Study Day 90.
Standard definitions of adverse events and serious adverse events were used.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 120 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
The study was designed and powered for evaluating DLTs and identifying a maximum tolerated dose, not for efficacy endpoints.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patrick Lyden, MD, FAAN, FAHA | Cedars-Sinai Medical Center | (310) 423-5166 | Patrick.Lyden@cshs.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 7, 2017 | Jul 27, 2018 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Oct 7, 2016 | Jul 27, 2018 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000591161 | 3K3A-APC protein |
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| University of Iowa |
| OTHER |
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|
| Placebo | Drug | Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion |
|
|
| Day 30 |
| PK of 3K3A-APC by Compartmental Analysis (Clearance) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
| PK of 3K3A-APC by Compartmental Analysis (Volume of Distribution) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
| PK of 3K3A-APC by Compartmental Analysis (Cmax) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
| PK of 3K3A-APC by Compartmental Analysis (AUC[0-inf]) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
| PK of 3K3A-APC by Compartmental Analysis (λz) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
| PK of 3K3A-APC by Compartmental Analysis (Half-life) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
| Chicago |
| Illinois |
| 60611 |
| United States |
| Stroke Center | Kansas City | Kansas | 66160 | United States |
| Stroke Center | Boston | Massachusetts | 02114 | United States |
| Stroke Center | St Louis | Missouri | 63110 | United States |
| Stroke Center | Buffalo | New York | 14209 | United States |
| Stroke Center | New York | New York | 10032 | United States |
| Stroke Center | Rochester | New York | 14642 | United States |
| Stroke Center | Cincinnati | Ohio | 45208 | United States |
| Stroke Center | Columbus | Ohio | 43210 | United States |
| Stroke Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Stroke Center | Nashville | Tennessee | 37232 | United States |
| Stroke Center | Dallas | Texas | 75390 | United States |
| Stroke Center | Salt Lake City | Utah | 84132 | United States |
| Stroke Center | Charlottesville | Virginia | 22904 | United States |
| 27803392 | Derived | Lyden P, Weymer S, Coffey C, Cudkowicz M, Berg S, O'Brien S, Fisher M, Haley EC, Khatri P, Saver J, Levine S, Levy H, Rymer M, Wechsler L, Jadhav A, McNeil E, Waddy S, Pryor K. Selecting Patients for Intra-Arterial Therapy in the Context of a Clinical Trial for Neuroprotection. Stroke. 2016 Dec;47(12):2979-2985. doi: 10.1161/STROKEAHA.116.013881. Epub 2016 Nov 1. |
| Withdrawal by Subject |
|
3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion
| BG002 | 360 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| BG003 | 540 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| BG004 | Placebo | Matching placebo, q12h for up to 5 doses Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| History of Hypertension | Count of Participants | Participants |
|
| History of Diabetes | Count of Participants | Participants |
|
| OG002 | 360 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| OG003 | 540 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion |
| OG004 | Placebo | Matching placebo, q12h for up to 5 doses Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion |
|
|
| Secondary | Number of Participants With a Presence of Measurable Bleeds in the Brain (Hemorrhage and Microbleeds) as Determined by 1.5T MRI | MRI examination to include-at minimum-T1 and T2 weighted images, as well as diffusion weighted imaging (DWI) and susceptibility weighted imaging (SWI) sequences. Post-tPA microbleeds-defined as hypointensities less than 5mm in diameter seen on SWI-will be counted as tPA-related only if found within the ischemic territory. All other areas of hypointensity on SWI larger than 5mm diameter will be counted as tPA-related regardless of the territory in which they are found. All treated subjects (regardless of dose) will be compared to all placebo subjects using a Pearson chi-square test. | Subjects with a Day 30 scan collected. | Posted | Count of Participants | Participants | Day 30 |
|
|
|
| Secondary | PK of 3K3A-APC by Compartmental Analysis (Clearance) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hr | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
|
|
|
| Secondary | PK of 3K3A-APC by Compartmental Analysis (Volume of Distribution) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
|
|
|
| Secondary | PK of 3K3A-APC by Compartmental Analysis (Cmax) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
|
|
|
| Secondary | PK of 3K3A-APC by Compartmental Analysis (AUC[0-inf]) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr▪ng/mL | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
|
|
|
| Secondary | PK of 3K3A-APC by Compartmental Analysis (λz) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/hr | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
|
|
|
| Secondary | PK of 3K3A-APC by Compartmental Analysis (Half-life) | Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters. | The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr | Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI |
|
|
|
| 0 |
| 15 |
| 8 |
| 15 |
| 10 |
| 15 |
| EG001 | 240 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion | 2 | 24 | 9 | 24 | 18 | 24 |
| EG002 | 360 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion | 3 | 12 | 4 | 12 | 8 | 12 |
| EG003 | 540 µg/kg of 3K3A-APC | 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion | 4 | 15 | 9 | 15 | 9 | 15 |
| EG004 | 3K3A-APC Total | All 3K3A-APC treated groups combined | 9 | 66 | 30 | 66 | 45 | 66 |
| EG005 | Placebo | Matching placebo, q12h for up to 5 doses Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion | 6 | 44 | 18 | 44 | 36 | 44 |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Cardiac arrest | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Intracardiac thrombus | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Pericarditis | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Duodenal ulcer haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Retroperitoneal haematoma | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | MedDRA | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA | Systematic Assessment |
|
| Blood sodium increased | Investigations | MedDRA | Systematic Assessment |
|
| Ejection fraction decreased | Investigations | MedDRA | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA | Systematic Assessment |
|
| Troponin increased | Investigations | MedDRA | Systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Carotid artery stenosis | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Cerebral haemorrhage | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Aneurysm repair | Surgical and medical procedures | MedDRA | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA | Systematic Assessment |
|
| Blood calcium decreased | Investigations | MedDRA | Systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | MedDRA | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA | Systematic Assessment |
|
| Prothrombin time prolonged | Investigations | MedDRA | Systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
Not provided
Not provided
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |