Albumin Replacement Therapy in Septic Shock

NCT ID: NCT03869385

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-21
• Study Completion Date: 2023-06-13

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

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Albumin group

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.

Group Type: EXPERIMENTAL

Albutein® 200 g/L or Plasbumin® 20

Intervention Type: 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.

Control group without albumin:

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Albutein® 200 g/L or Plasbumin® 20

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.

Intervention Type: DRUG

Other Intervention Names

Human Albumin 20%

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Research Foundation

OTHER

Sponsor Role: collaborator

Instituto Grifols, S.A.

INDUSTRY

Sponsor Role: collaborator

University Hospital Goettingen

OTHER

Sponsor Role: collaborator

SepNet - Critical Care Trials Group

OTHER

Sponsor Role: collaborator

Center for Sepsis Control and Care, Germany

OTHER

Sponsor Role: collaborator

Jena University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yasser Sakr

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yasser Sakr, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Jena University Hospital

Locations

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

St. Elisabeth Krankenhaus, Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie

Cologne, , Germany

Universitätsklinikum Erlangen, Anästesiologische Klinik

Erlangen, , Germany

Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie, Chir. Intensivstation

Freiburg im Breisgau, , Germany

Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Rettungs- und Intensivmedizin

Göttingen, , Germany

Universitätsmedizin Greifswald, Klinik für Anästhesiologie, Intensiv-, Notfall- und Schmerzmedizin

Greifswald, , 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

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

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 33287911 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-001874-89

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SA 2167/3-1, Nr: 328809707

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ZKSJ0112

Identifier Type: OTHER

Identifier Source: secondary_id

ZKSJ0112_ARISS

Identifier Type: -

Identifier Source: org_study_id