Albumin Replacement Therapy in Septic Shock (ARISS)

Randomised Controlled Multicentre Study of Albumin Replacement Therapy in Septic Shock

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.

Study Overview

• Status: Terminated
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Albutein® 200 g/L or Plasbumin® 20

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

• Study Type: Interventional
• Enrollment (Actual): 440
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Augsburg, Germany, 86156
    • Klinikum Augsburg, Klinik für Anästhesiologie und Operative Intensivmedizin
  • Bad Saarow, Germany, 15526
    • Helios Klinikum Bad Saarow, Klinik für Intensivmedizin
  • Berlin, Germany, 13509
    • Vivantes Humboldt Klinikum, Klinik für Innere Medizin, Kardiologie und konservative Intensivmedizin
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn, Klinik für Anästesiologie und Operative Intensivmedizin
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen, Anästesiologische Klinik
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie, Chir. Intensivstation
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald, Klinik für Anästhesiologie, Intensiv-, Notfall- und Schmerzmedizin
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Rettungs- und Intensivmedizin
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf, Klinik für Intensivmedizin
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg, Klinik für Anästhesiologie
  • Herford, Germany, 32049
    • Klinikum Herford, Medizinische Klinik III, Kardiologie
  • Herne, Germany, 44625
    • Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerztherapie, Palliativmedizin
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
  • Jena, Germany, 07747
    • Universitätsklinikum Jena, Innere Medizin I, Kardiologie
  • Jena, Germany, 07747
    • Universitätsklinikum Jena, Klinik für Innere Medizin I, Kardiologie
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein, Klinik für Operative Intensivmedizin
  • Köln, Germany, 50935
    • St. Elisabeth Krankenhaus, Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig, Interdisziplinäre Internistische Intensivmedizin
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig, Klinik für Anästhesiologie u. Intensivtherapie
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg, Klinik für Innere Medizin, Kardiologie und Angiologie
  • Magdeburg, Germany
    • Universitätsklinikum Magdeburg, Klinik für Anästhesiologie und Intensivmedizin
  • Mainz, Germany, 55131
    • Universitätsklinikum der Johannes-Gutenberg-Universität Mainz, Klinik für Anästhesiologie
  • München, Germany, 81377
    • Klinikum der LMU München, Klinik für Anästhesiologie
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU München, Klinik für Anästhesiologie und Intensivmedizin
  • Münster, Germany, 48149
    • Universitätsklinikum Münster, Klinik für Anästesiologie, operative Intensivmedizin und Schmerztherapie
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.; Other Names: Human Albumin 20%
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day All Cause Mortality	Mortality within 90 days after randomisation	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day Mortality	Mortality within 28 days after randomisation	28 days
60-day Mortality	Mortality within 60 days after randomisation	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

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Collaborators: German Research Foundation; Instituto Grifols, S.A.; University Hospital Goettingen; SepNet - Critical Care Trials Group; Center for Sepsis Control and Care, Germany
• Investigators: Principal Investigator: Yasser Sakr, MD, PhD, Jena University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2019
• Primary Completion (Actual): July 27, 2022
• Study Completion (Actual): June 13, 2023

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 11, 2019

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 25, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Sepsis; Human albumin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Shock, Septic
• Other Study ID Numbers: ZKSJ0112_ARISS; 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)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes