Albumin Replacement Therapy in Septic Shock

Septic Shock Clinical Trial

— ARISS  

Official title:

Randomised Controlled Multicentre Study of Albumin Replacement Therapy in Septic Shock

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03869385
• Other study ID #: ZKSJ0112_ARISS
• Secondary ID: 2018-001874-89SA
• Status: Recruiting
• Phase: Phase 3
• Start date: October 21, 2019
• Est. completion date: January 30, 2023

Study information

• Verified date: June 2021
• Source: Jena University Hospital
• Contact: Yasser Sakr, MD, PhD
• Phone: 01742191538
• Email: yasser.sakr[@]med.uni-jena.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1662
• Est. completion date: January 30, 2023
• Est. primary completion date: October 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

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.

Locations

Country	Name	City	State
Germany	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	Universitätsklinikum Erlangen, Anästesiologische Klinik	Erlangen
Germany	Universitätsklinikum Freiburg, Klinik für Allgemein- und Viszeralchirurgie, Chir. Intensivstation	Freiburg
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	St. Elisabeth Krankenhaus, Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie	Köln
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 Anästhesiologie und Intensivmedizin	Magdeburg
Germany	Universitätsklinikum Magdeburg, Klinik für Innere Medizin, Kardiologie und Angiologie	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

Sponsors (7)

Lead Sponsor	Collaborator
Jena University Hospital	Center for Sepsis Control and Care, Germany, German Research Foundation, Instituto Grifols, S.A., SepNet - Critical Care Trials Group, The Center for Clinical Trials (ZKS), Jena, University Hospital Goettingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	90-day all cause mortality	Mortality within 90 days after randomisation	90 days
Secondary	28-day mortality	Mortality within 28 days after randomisation	28 days
Secondary	60-day mortality	Mortality within 60 days after randomisation	60 days
Secondary	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
Secondary	Sequential Organ Failure Assessement (SOFA) score	The overall degree of organ dysfunction/failure assessed daily by the total SOFA score (range 0-24 points), with higher scores indicating higher degree of overall organ dysfunction/failure).	28 days
Secondary	ICU length of stay	ICU stay of first hospitalization after randomisation within 90 days	90 days
Secondary	Hospital length of stay	Hospital stay of first hospitalization after randomisation within 90 days	90 days
Secondary	Ventilation-free days	Ventilation-free days within 28 days after randomisation	28 days
Secondary	Vasopressor-free days	Vasopressor-free days within 28 days after randomisation	28 days
Secondary	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