Clinical trial NCT03869385: Albumin Replacement Therapy in Septic Shock
Official title: Randomised Controlled Multicentre Study of Albumin Replacement Therapy in Septic Shock
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Septic Shock
Keywords: Human albumin
Sepsis
Lead sponsor: Jena University Hospital
Sponsor class: OTHER
Collaborators: name: German Research Foundation
name: Instituto Grifols, S.A.
name: University Hospital Goettingen
name: SepNet - Critical Care Trials Group
name: Center for Sepsis Control and Care, Germany
First posted: 2019-03-11
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 90-day All Cause Mortality
timeFrame: 90 days
Secondary outcomes:
measure: 28-day Mortality
timeFrame: 28 days
measure: 60-day Mortality
timeFrame: 60 days
measure: Organ Failure
timeFrame: 28 days
measure: Sequential Organ Failure Assessement (SOFA) Score
timeFrame: 28 days
measure: ICU Length of Stay
timeFrame: 90 days
measure: Hospital Length of Stay
timeFrame: 90 days
measure: Ventilation-free Days
timeFrame: 28 days
measure: Vasopressor-free Days
timeFrame: 28 days
measure: Total Amount of Fluid of Fluid Administration and Total Fluid Balance in the ICU.
timeFrame: 28 days
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Klinikum Augsburg, Klinik für Anästhesiologie und Operative Intensivmedizin
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow, Klinik für Intensivmedizin
city: Berlin
country: Germany
facility: Vivantes Humboldt Klinikum, Klinik für Innere Medizin, Kardiologie und konservative Intensivmedizin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Klinik für Anästesiologie und Operative Intensivmedizin
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Anästesiologische Klinik
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie, Chir. Intensivstation
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Klinik für Anästhesiologie, Intensiv-, Notfall- und Schmerzmedizin
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Rettungs- und Intensivmedizin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Klinik für Anästhesiologie
city: Herford
country: Germany
facility: Klinikum Herford, Medizinische Klinik III, Kardiologie
city: Herne
country: Germany
facility: Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerztherapie, Palliativmedizin
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Innere Medizin I, Kardiologie
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Innere Medizin I, Kardiologie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Klinik für Operative Intensivmedizin
city: Köln
country: Germany
facility: St. Elisabeth Krankenhaus, Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Interdisziplinäre Internistische Intensivmedizin
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik für Anästhesiologie u. Intensivtherapie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg, Klinik für Innere Medizin, Kardiologie und Angiologie
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg, Klinik für Anästhesiologie und Intensivmedizin
city: Mainz
country: Germany
facility: Universitätsklinikum der Johannes-Gutenberg-Universität Mainz, Klinik für Anästhesiologie
city: München
country: Germany
facility: Klinikum der LMU München, Klinik für Anästhesiologie
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München, Klinik für Anästhesiologie und Intensivmedizin
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Anästesiologie, operative Intensivmedizin und Schmerztherapie
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie
Study officials:
affiliation: Jena University Hospital
name: Yasser Sakr, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.