Albumin Replacement Therapy in Septic Shock

NCT03869385 | Terminated Phase 3 Results DMC

• 4 other identifiers: ZKSJ0112_ARISS2018-001874-89SA 2167/3-1, Nr: 328809707ZKSJ0112
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 27

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.

Conditions

Septic Shock

Keywords

Human albumin; Sepsis

Outcome Measures

Primary Outcomes (1)

• 90-day All Cause Mortality

  Mortality within 90 days after randomisation

  90 days

Secondary Outcomes (9)

• 28-day Mortality

  28 days

• 60-day Mortality

  60 days

• Organ Failure

  28 days

• Sequential Organ Failure Assessement (SOFA) Score

  28 days

• ICU Length of Stay

  90 days

Study Arms (2)

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.

Drug: Albutein® 200 g/L or Plasbumin® 20

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.

Interventions

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.

Also known as: Human Albumin 20%

Albumin group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jena University Hospital: lead
• German Research Foundation: collaborator
• Instituto Grifols, S.A.: collaborator
• University Hospital Goettingen: collaborator
• SepNet - Critical Care Trials Group: collaborator
• Center for Sepsis Control and Care, Germany: collaborator

Study Sites (27)

Klinikum Augsburg, Klinik für Anästhesiologie und Operative Intensivmedizin

Augsburg, 86156, Germany

Location

Helios Klinikum Bad Saarow, Klinik für Intensivmedizin

Bad Saarow, 15526, Germany

Location

Vivantes Humboldt Klinikum, Klinik für Innere Medizin, Kardiologie und konservative Intensivmedizin

Berlin, 13509, Germany

Location

Universitätsklinikum Bonn, Klinik für Anästesiologie und Operative Intensivmedizin

Bonn, 53105, Germany

Location

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

Cologne, 50935, Germany

Location

Universitätsklinikum Erlangen, Anästesiologische Klinik

Erlangen, 91054, Germany

Location

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

Freiburg im Breisgau, 79106, Germany

Location

Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Rettungs- und Intensivmedizin

Göttingen, 37075, Germany

Location

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

Greifswald, 17475, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg, Klinik für Anästhesiologie

Heidelberg, 69120, Germany

Location

Klinikum Herford, Medizinische Klinik III, Kardiologie

Herford, 32049, Germany

Location

Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerztherapie, Palliativmedizin

Herne, 44625, Germany

Location

Universitätsklinikum des Saarlandes, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie

Homburg, 66421, Germany

Location

Universitätsklinikum Jena, Innere Medizin I, Kardiologie

Jena, 07747, Germany

Location

Universitätsklinikum Jena, Klinik für Innere Medizin I, Kardiologie

Jena, 07747, Germany

Location

Universitätsklinikum Schleswig-Holstein, Klinik für Operative Intensivmedizin

Kiel, 24105, Germany

Location

Universitätsklinikum Leipzig, Interdisziplinäre Internistische Intensivmedizin

Leipzig, 04103, Germany

Location

Universitätsklinikum Leipzig, Klinik für Anästhesiologie u. Intensivtherapie

Leipzig, 04103, Germany

Location

Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie

Leipzig, 04103, Germany

Location

Universitätsklinikum Magdeburg, Klinik für Innere Medizin, Kardiologie und Angiologie

Magdeburg, 39120, Germany

Location

Universitätsklinikum Magdeburg, Klinik für Anästhesiologie und Intensivmedizin

Magdeburg, Germany

Location

Universitätsklinikum der Johannes-Gutenberg-Universität Mainz, Klinik für Anästhesiologie

Mainz, 55131, Germany

Location

Klinikum der LMU München, Klinik für Anästhesiologie

München, 81377, Germany

Location

Klinikum rechts der Isar der TU München, Klinik für Anästhesiologie und Intensivmedizin

München, 81675, Germany

Location

Universitätsklinikum Münster, Klinik für Anästesiologie, operative Intensivmedizin und Schmerztherapie

Münster, 48149, Germany

Location

Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie

Regensburg, 93053, Germany

Location

Related Publications (1)

• 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.

  PMID: 33287911 DERIVED

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Albumins

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Prof. Dr. Yasser Sakr
• Organization: University Hospital of Jena

yasser.sakr@med.uni-jena.de

01742191538

Study Officials

• Yasser Sakr, MD, PhD

  Jena University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 11, 2019
• Study Start: October 21, 2019
• Primary Completion: July 27, 2022
• Study Completion: June 13, 2023
• Last Updated: October 28, 2024
• Results First Posted: October 28, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (27)