Albumin Replacement Therapy in Septic Shock
- Registration Number
- NCT03869385
- Lead Sponsor
- Jena University Hospital
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 440
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The presence of septic shock meeting all of the following criteria:
- Clinically possible or probable or microbiologically confirmed infection taking into account the definitions of the "International Sepsis Forum (ISF)"
- Despite adequate volume therapy, vasopressors are required to maintain mean arterial pressure (MAP) ≥ 65 mm Hg for at least 1 hour
- Serum lactate level > 2 mmol/l (18 mg/dl) despite adequate volume therapy
-
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
- Moribund conditions with life expectancy less than 28 days because of comorbid conditions or advanced malignant disease and palliative situations with life expectancy less than 6 months
- Presence of an "end of life" decision prior to obtaining informed consent: "Do Not Resuscitate (DNR)" and "Withhold/Withdraw Life-Sustaining measures"
- Previous participation in this study
- Participation in another interventional clinical trial within the past 3 months
- Shock states that can be explained by other causes, e.g. cardiogenic shock, anaphylactic shock, neurogenic shock
- History of hypersensitivity to albumin or any other component of the trial drug, e.g., B., sodium caprylate, sodium N-acetyltryptophanate
- Diseases in which albumin administration may be deleterious, e.g., decompensated heart failure or traumatic brain injury
- Clinical conditions where albumin administration is indicated, e.g., hepatorenal syndrome, nephrosis, burns, intestinal malabsorption syndrome
- Lactation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Albumin group Albutein® 200 g/L or Plasbumin® 20 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.
- Primary Outcome Measures
Name Time Method 90-day All Cause Mortality 90 days Mortality within 90 days after randomisation
- Secondary Outcome Measures
Name Time Method 28-day Mortality 28 days Mortality within 28 days after randomisation
60-day Mortality 60 days Mortality within 60 days after randomisation
Organ Failure 28 days 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
Sequential Organ Failure Assessement (SOFA) Score 28 days 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).
ICU Length of Stay 90 days Intensive Care unit stay of first hospitalization after randomisation within 90 days
Hospital Length of Stay 90 days Hospital stay of first hospitalization after randomisation within 90 days
Ventilation-free Days 28 days Ventilation-free days within 28 days after randomisation
Vasopressor-free Days 28 days Vasopressor-free days within 28 days after randomisation
Total Amount of Fluid of Fluid Administration and Total Fluid Balance in the ICU. 28 days Total amount of fluid of fluid administration and total fluid balance in the ICU within 28 days after randomisation
Trial Locations
- Locations (27)
Klinikum Augsburg, Klinik für Anästhesiologie und Operative Intensivmedizin
🇩🇪Augsburg, Germany
Helios Klinikum Bad Saarow, Klinik für Intensivmedizin
🇩🇪Bad Saarow, Germany
Vivantes Humboldt Klinikum, Klinik für Innere Medizin, Kardiologie und konservative Intensivmedizin
🇩🇪Berlin, Germany
Universitätsklinikum Bonn, Klinik für Anästesiologie und Operative Intensivmedizin
🇩🇪Bonn, Germany
Universitätsklinikum Erlangen, Anästesiologische Klinik
🇩🇪Erlangen, Germany
Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie, Chir. Intensivstation
🇩🇪Freiburg, Germany
Universitätsmedizin Greifswald, Klinik für Anästhesiologie, Intensiv-, Notfall- und Schmerzmedizin
🇩🇪Greifswald, Germany
Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Rettungs- und Intensivmedizin
🇩🇪Göttingen, Germany
Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin
🇩🇪Hamburg, Germany
Universitätsklinikum Heidelberg, Klinik für Anästhesiologie
🇩🇪Heidelberg, Germany
Klinikum Herford, Medizinische Klinik III, Kardiologie
🇩🇪Herford, Germany
Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerztherapie, Palliativmedizin
🇩🇪Herne, Germany
Universitätsklinikum des Saarlandes, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
🇩🇪Homburg, Germany
Universitätsklinikum Jena, Innere Medizin I, Kardiologie
🇩🇪Jena, Germany
Universitätsklinikum Jena, Klinik für Innere Medizin I, Kardiologie
🇩🇪Jena, Germany
Universitätsklinikum Schleswig-Holstein, Klinik für Operative Intensivmedizin
🇩🇪Kiel, Germany
St. Elisabeth Krankenhaus, Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie
🇩🇪Köln, Germany
Universitätsklinikum Leipzig, Interdisziplinäre Internistische Intensivmedizin
🇩🇪Leipzig, Germany
Universitätsklinikum Leipzig, Klinik für Anästhesiologie u. Intensivtherapie
🇩🇪Leipzig, Germany
Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie
🇩🇪Leipzig, Germany
Universitätsklinikum Magdeburg, Klinik für Innere Medizin, Kardiologie und Angiologie
🇩🇪Magdeburg, Germany
Universitätsklinikum Magdeburg, Klinik für Anästhesiologie und Intensivmedizin
🇩🇪Magdeburg, Germany
Universitätsklinikum der Johannes-Gutenberg-Universität Mainz, Klinik für Anästhesiologie
🇩🇪Mainz, Germany
Klinikum der LMU München, Klinik für Anästhesiologie
🇩🇪München, Germany
Klinikum rechts der Isar der TU München, Klinik für Anästhesiologie und Intensivmedizin
🇩🇪München, Germany
Universitätsklinikum Münster, Klinik für Anästesiologie, operative Intensivmedizin und Schmerztherapie
🇩🇪Münster, Germany
Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie
🇩🇪Regensburg, Germany