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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001874-89 | EudraCT Number | ||
| SA 2167/3-1, Nr: 328809707 | Other Grant/Funding Number | Deutsche Forschungsgemeinschaft (DFG) | |
| ZKSJ0112 | Other Identifier | Trial code, ZKS Jena |
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Sustained low inclusion rates.
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| Name | Class |
|---|---|
| German Research Foundation | OTHER |
| Instituto Grifols, S.A. | INDUSTRY |
| University Hospital Goettingen | OTHER |
| SepNet - Critical Care Trials Group |
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Albumin is a key regulator of fluid distribution within the extracellular space and possesses several properties beyond its oncotic activity, including binding and transport of several endogenous molecules, anti-inflammatory and anti-oxidant actions, nitric oxide modulation, and buffer function. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock. Prospective randomized trials on the possible impact of albumin replacement in these patients with septic shock are lacking. The aim of the study is to investigate whether the replacement with albumin and the maintenance of its serum levels at least at 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. In this prospective, multicenter, randomised trial, adult patients (≥18 years) with septic shock will be randomly assigned within a maximum of 24 hours after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group will receive a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels will be maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. The control group will be treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary end point is 90 days mortality and secondary end points include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, and length of ICU and hospital stay. In total 1412 patients need to be analyzed, 706 per group. Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated.
This is a prospective, multicentre, randomised, controlled, parallel-grouped, open-label, interventional clinical trial in which 1662 patients are planned to be allocated. Subjects will be randomized in a 1:1 ratio to receive either Albumin or routine treatment with crystalloids. Treatment will be continued at maximum for 28 days or until the patient leaves the ICU. Primary endpoint measurement will be carried out 90 days after randomisation
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Albumin group | Experimental | Patients assigned to the Albumin group will receive a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels will be maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. |
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| Control group without albumin: | No Intervention | The control group will be treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albutein® 200 g/L or Plasbumin® 20 | Drug | The initial dose of the trial drug must be started within 6 to 24 hours after the beginning of the septic shock. Starting dose: 60 g human albumin 20% (Albutein® 200 g/L, infusion solution) over 2-3 h Daily administration of the trial drug will be based on the serum albumin concentration measured each day. Dose adjustment will follow a predetermined schedule with the aim of maintaining a serum albumin concentration of at least 30 g/l. Administration of the trial drug will continue for a maximum of 28 study days after randomisation and only as long as the participant is being treated in the ICU. |
| Measure | Description | Time Frame |
|---|---|---|
| 90-day All Cause Mortality | Mortality within 90 days after randomisation | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| 28-day Mortality | Mortality within 28 days after randomisation | 28 days |
| 60-day Mortality | Mortality within 60 days after randomisation |
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Inclusion Criteria:
The presence of septic shock meeting all of the following criteria:
Start of septic shock less than 24 hours prior to inclusion, so that the start dose of the trial drug in the albumin group will be possible within 6-24 hours after the start of the septic shock
Age: ≥ 18 years
Written informed consent of the patient or his/her legal representative or confirmation of the urgency of participation in the clinical trial and possible benefit to the patient by an independent consultant or the implementation of other established procedures according to the local regulations of the contributing centre to include patients who are unable to provide informed consent in whom subsequent consent may be obtained retrospectively.
Patients of childbearing age: negative pregnancy test
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yasser Sakr, MD, PhD | Jena University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Klinikum Augsburg, Klinik für Anästhesiologie und Operative Intensivmedizin | Augsburg | 86156 | Germany | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41712212 | Derived | Sakr Y, Nierhaus A, Schumacher U, Utzolino S, Jaschinski U, Petros S, Fichtner F, Eimer C, Putensen C, Tanev I, Kreienbuhl L, Kluge S, Kousoulas L, Kuhn SO, Jarczak D, Quintel M, Bauer M; SepNet Critical Care Trials Group and Albumin Replacement Therapy in Septic Shock (ARISS) investigators. Albumin Replacement Therapy in Septic Shock: A Randomized Clinical Trial. JAMA Netw Open. 2026 Feb 2;9(2):e2559297. doi: 10.1001/jamanetworkopen.2025.59297. | |
| 33287911 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Albumin Group | Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. |
| FG001 | Control Group Without Albumin: |
| 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 | Jul 18, 2019 | Sep 17, 2019 |
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| OTHER |
| Center for Sepsis Control and Care, Germany | OTHER |
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| 60 days |
| Organ Failure | Organ failure defined as increase in the daily recorded Sequential organ Failure Assessement (SOFA) subscores; cardiovascular, respiratory, hematologic, hepatic, renal, neurologic (range 0-4 points each) from a value <2 to a value ≥ 2 | 28 days |
| Sequential Organ Failure Assessement (SOFA) Score | The overall degree of organ dysfunction/failure assessed daily by the total Sequential Organ Failure Score (SOFA score: range 0-24 points), with higher scores indicating higher degree of overall organ dysfunction/failure). | 28 days |
| ICU Length of Stay | Intensive Care unit stay of first hospitalization after randomisation within 90 days | 90 days |
| Hospital Length of Stay | Hospital stay of first hospitalization after randomisation within 90 days | 90 days |
| Ventilation-free Days | Ventilation-free days within 28 days after randomisation | 28 days |
| Vasopressor-free Days | Vasopressor-free days within 28 days after randomisation | 28 days |
| Total Amount of Fluid of Fluid Administration and Total Fluid Balance in the ICU. | Total amount of fluid of fluid administration and total fluid balance in the ICU within 28 days after randomisation | 28 days |
| Helios Klinikum Bad Saarow, Klinik für Intensivmedizin |
| Bad Saarow |
| 15526 |
| Germany |
| Vivantes Humboldt Klinikum, Klinik für Innere Medizin, Kardiologie und konservative Intensivmedizin | Berlin | 13509 | Germany |
| Universitätsklinikum Bonn, Klinik für Anästesiologie und Operative Intensivmedizin | Bonn | 53105 | Germany |
| St. Elisabeth Krankenhaus, Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie | Cologne | 50935 | Germany |
| Universitätsklinikum Erlangen, Anästesiologische Klinik | Erlangen | 91054 | Germany |
| Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie, Chir. Intensivstation | Freiburg im Breisgau | 79106 | Germany |
| Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Rettungs- und Intensivmedizin | Göttingen | 37075 | Germany |
| Universitätsmedizin Greifswald, Klinik für Anästhesiologie, Intensiv-, Notfall- und Schmerzmedizin | Greifswald | 17475 | Germany |
| Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin | Hamburg | 20246 | Germany |
| Universitätsklinikum Heidelberg, Klinik für Anästhesiologie | Heidelberg | 69120 | Germany |
| Klinikum Herford, Medizinische Klinik III, Kardiologie | Herford | 32049 | Germany |
| Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerztherapie, Palliativmedizin | Herne | 44625 | Germany |
| Universitätsklinikum des Saarlandes, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie | Homburg | 66421 | Germany |
| Universitätsklinikum Jena, Innere Medizin I, Kardiologie | Jena | 07747 | Germany |
| Universitätsklinikum Jena, Klinik für Innere Medizin I, Kardiologie | Jena | 07747 | Germany |
| Universitätsklinikum Schleswig-Holstein, Klinik für Operative Intensivmedizin | Kiel | 24105 | Germany |
| Universitätsklinikum Leipzig, Interdisziplinäre Internistische Intensivmedizin | Leipzig | 04103 | Germany |
| Universitätsklinikum Leipzig, Klinik für Anästhesiologie u. Intensivtherapie | Leipzig | 04103 | Germany |
| Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie | Leipzig | 04103 | Germany |
| Universitätsklinikum Magdeburg, Klinik für Innere Medizin, Kardiologie und Angiologie | Magdeburg | 39120 | Germany |
| Universitätsklinikum Magdeburg, Klinik für Anästhesiologie und Intensivmedizin | Magdeburg | Germany |
| Universitätsklinikum der Johannes-Gutenberg-Universität Mainz, Klinik für Anästhesiologie | Mainz | 55131 | Germany |
| Klinikum der LMU München, Klinik für Anästhesiologie | München | 81377 | Germany |
| Klinikum rechts der Isar der TU München, Klinik für Anästhesiologie und Intensivmedizin | München | 81675 | Germany |
| Universitätsklinikum Münster, Klinik für Anästesiologie, operative Intensivmedizin und Schmerztherapie | Münster | 48149 | Germany |
| Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie | Regensburg | 93053 | Germany |
| Derived |
| Sakr Y, Bauer M, Nierhaus A, Kluge S, Schumacher U, Putensen C, Fichtner F, Petros S, Scheer C, Jaschinski U, Tanev I, Jacob D, Weiler N, Schulze PC, Fiedler F, Kapfer B, Brunkhorst F, Lautenschlaeger I, Wartenberg K, Utzolino S, Briegel J, Moerer O, Bischoff P, Zarbock A, Quintel M, Gattinoni L; SepNet - Critical Care Trials Group. Randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS): protocol for a randomized controlled trial. Trials. 2020 Dec 7;21(1):1002. doi: 10.1186/s13063-020-04921-y. |
The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. |
| COMPLETED |
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| NOT COMPLETED |
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Informed consents were not possible to obtain within 72 hours after randomization in 14 patients, 4 patients were lost to follow up, 2 patients withdrew the informed consent, and the study was terminated in one patient due to investigator decision. Therefore, the primary outcome parameter was available for analysis in 210 patients in the albumin and 209 patients in the control groups
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| ID | Title | Description |
|---|---|---|
| BG000 | Albumin Group | Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. |
| BG001 | Control Group Without Albumin: | The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The demographic and baseline characteristics were similar between the study groups. |
| BG002 | 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 | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Blood lactate level | Median | Inter-Quartile Range | mmol/liter |
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| Serum albumin | Mean | Standard Deviation | g/liter |
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| 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 | 90-day All Cause Mortality | Mortality within 90 days after randomisation | Informed consents were not possible to obtain within 72 hours after randomization in 14 patients, 4 patients were lost to follow up, 2 patients withdrew the informed consent, and the study was terminated in one patient due to investigator decision. Therefore, the primary outcome parameter was available for analysis in 210 patients in the albumin and 209 patients in the control groups | Posted | Count of Participants | Participants | 90 days |
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| Secondary | 28-day Mortality | Mortality within 28 days after randomisation | At 28 days after randomization, informed consent was not possible to be obtained within 72 hours of randomization in 14 patients, 2 patients withdrew consent, and the study was terminated in one patient due to investigator decision. Therefore, 28-days mortality were available in 213 vs. 210 patients in the albumin vs. control group, respectively | Posted | Count of Participants | Participants | 28 days |
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| Secondary | 60-day Mortality | Mortality within 60 days after randomisation | At 60 days after randomization, informed consent was not possible to be obtained within 72 hours of randomization in 14 patients, 2 patients withdrew consent, 2 patients were lost to follow-up, and the study was terminated in one patient due to investigator decision. Therefore, 60-days mortality were available in 211 vs. 210 patients in the albumin vs. control group, respectively | Posted | Count of Participants | Participants | 60 days |
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| Secondary | Organ Failure | Organ failure defined as increase in the daily recorded Sequential organ Failure Assessement (SOFA) subscores; cardiovascular, respiratory, hematologic, hepatic, renal, neurologic (range 0-4 points each) from a value <2 to a value ≥ 2 | Posted | Number | participants | 28 days |
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| Secondary | Sequential Organ Failure Assessement (SOFA) Score | The overall degree of organ dysfunction/failure assessed daily by the total Sequential Organ Failure Score (SOFA score: range 0-24 points), with higher scores indicating higher degree of overall organ dysfunction/failure). | Posted | Mean | Standard Deviation | Points | 28 days |
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| Secondary | ICU Length of Stay | Intensive Care unit stay of first hospitalization after randomisation within 90 days | Posted | Median | Inter-Quartile Range | Days | 90 days |
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| Secondary | Hospital Length of Stay | Hospital stay of first hospitalization after randomisation within 90 days | Posted | Median | Inter-Quartile Range | Days | 90 days |
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| Secondary | Ventilation-free Days | Ventilation-free days within 28 days after randomisation | Posted | Median | Inter-Quartile Range | Days | 28 days |
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| Secondary | Vasopressor-free Days | Vasopressor-free days within 28 days after randomisation | Posted | Median | Inter-Quartile Range | Days | 28 days |
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| Secondary | Total Amount of Fluid of Fluid Administration and Total Fluid Balance in the ICU. | Total amount of fluid of fluid administration and total fluid balance in the ICU within 28 days after randomisation | Posted | Median | Inter-Quartile Range | ml/day | 28 days |
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In the albumin group until 24 h after the last dose of the trial drug Iin the control group without albumin until day 28 after randomisation or until discharge from the ICU, if it occurs before day 28 after randomisation. In the event that adverse events are still "ongoing" after the above dates, they were tracked until maximum the end of data collection (Day 90). If they are "ongoing" on day 90, they were documented as "not recovered," "recovered with sequelae," or "unknown."
Events plausibly explainable by sepsis were recorded in both groups as sepsis-related clinical events, but not as adverse events (AEs). Documentation of the sepsis-related clinical event as an AE occurs only if the examiner suspects a connection with the administration of the trial drug, which is therefore only possible in the albumin group. Clinically relevant worsening of a pre-existing disease not related to sepsis was considered and documented as an AE.
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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 | Albumin Group | Patients assigned to the Albumin group received a 60 g loading dose of human albumin 20% over 2-3 hours. Serum albumin levels were maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. | 91 | 222 | 3 | 222 | 183 | 222 |
| EG001 | Control Group Without Albumin: | The control group was treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. | 96 | 218 | 2 | 218 | 176 | 218 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypervolemia | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis related, Cardiovascular events | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Dr. Yasser Sakr | University Hospital of Jena | 01742191538 | 0049 | yasser.sakr@med.uni-jena.de |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 6, 2023 | Jul 13, 2023 | SAP_003.pdf |
| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
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| ID | Term |
|---|---|
| D000418 | Albumins |
| ID | Term |
|---|---|
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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The control group will be treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock.
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