Albumin Replacement Therapy in Septic Shock (ARISS)

October 25, 2024 updated by: Yasser Sakr, Jena University Hospital

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
440

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
90-day All Cause Mortality
Time Frame: 90 days
Mortality within 90 days after randomisation
90 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
28-day Mortality
Time Frame: 28 days
Mortality within 28 days after randomisation
28 days
60-day Mortality
Time Frame: 60 days
Mortality within 60 days after randomisation
60 days
Organ Failure
Time Frame: 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
28 days
Sequential Organ Failure Assessement (SOFA) Score
Time Frame: 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).
28 days
ICU Length of Stay
Time Frame: 90 days
Intensive Care unit stay of first hospitalization after randomisation within 90 days
90 days
Hospital Length of Stay
Time Frame: 90 days
Hospital stay of first hospitalization after randomisation within 90 days
90 days
Ventilation-free Days
Time Frame: 28 days
Ventilation-free days within 28 days after randomisation
28 days
Vasopressor-free Days
Time Frame: 28 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.
Time Frame: 28 days
Total amount of fluid of fluid administration and total fluid balance in the ICU within 28 days after randomisation
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jena University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
German Research Foundation
Instituto Grifols, S.A.
University Hospital Goettingen
SepNet - Critical Care Trials Group
Center for Sepsis Control and Care, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yasser Sakr, MD, PhD, Jena University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 21, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 27, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 13, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 11, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings