NCT03869385: ARISS

Albumin Replacement Therapy in Septic Shock

Terminated Phase 3 Results posted Last updated 28 October 2024

What this trial tests

Phase 3 trial testing Albutein® 200 g/L or Plasbumin® 20 in Septic Shock in 440 participants. Terminated before completion.

Timeline

21 October 2019

Primary endpoint
27 July 2022

13 June 2023

Quick facts

Lead sponsor	Jena University Hospital
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	440
Start date	21 October 2019
Primary completion	27 July 2022
Estimated completion	13 June 2023
Sites	27 locations across Germany

Drugs / interventions tested

• Albutein® 200 g/L or Plasbumin® 20 — full drug profile →

Conditions studied

• Septic Shock — all drugs for Septic Shock →

Sponsor

Jena University Hospital

Who can join

18 and older, any sex, with Septic Shock. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

90-day All Cause Mortality Primary · 90 days

Mortality within 90 days after randomisation

Group	Value	95% CI
Albumin Group	91
Control Group Without Albumin:	96

28-day Mortality Secondary · 28 days

Mortality within 28 days after randomisation

Group	Value	95% CI
Albumin Group	66
Control Group Without Albumin:	80

60-day Mortality Secondary · 60 days

Mortality within 60 days after randomisation

Group	Value	95% CI
Albumin Group	82
Control Group Without Albumin:	95

Organ Failure Secondary · 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

1 organ failure

Group	Value	95% CI
Albumin Group	68
Control Group Without Albumin:	52

2 organ failures

Group	Value	95% CI
Albumin Group	19
Control Group Without Albumin:	14

3 organ failures

Group	Value	95% CI
Albumin Group	2
Control Group Without Albumin:	7

4 organ failures

Group	Value	95% CI
Albumin Group	0
Control Group Without Albumin:	1

Sequential Organ Failure Assessement (SOFA) Score Secondary · 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).

Group	Value	95% CI
Albumin Group	9	± 0.5
Control Group Without Albumin:	8.6	± 0.7

ICU Length of Stay Secondary · 90 days

Intensive Care unit stay of first hospitalization after randomisation within 90 days

Group	Value	95% CI
Albumin Group	13	7 – 22
Control Group Without Albumin:	12	7 – 29

Hospital Length of Stay Secondary · 90 days

Hospital stay of first hospitalization after randomisation within 90 days

Group	Value	95% CI
Albumin Group	24	15 – 42
Control Group Without Albumin:	27	14 – 45

Ventilation-free Days Secondary · 28 days

Ventilation-free days within 28 days after randomisation

Group	Value	95% CI
Albumin Group	4	1 – 7
Control Group Without Albumin:	3	0 – 7

Vasopressor-free Days Secondary · 28 days

Vasopressor-free days within 28 days after randomisation

Group	Value	95% CI
Albumin Group	2.5	0 – 7
Control Group Without Albumin:	2	0 – 6

Total Amount of Fluid of Fluid Administration and Total Fluid Balance in the ICU. Secondary · 28 days

Total amount of fluid of fluid administration and total fluid balance in the ICU within 28 days after randomisation

Total amount of fluid adminstration

Group	Value	95% CI
Albumin Group	3200	2502 – 3544
Control Group Without Albumin:	3693	2540 – 4443

Total fluid balance

Group	Value	95% CI
Albumin Group	234	-491 – 1290
Control Group Without Albumin:	355	-402 – 1576

Adverse events — posted to ClinicalTrials.gov

Time frame: In the albumin group until 24 h after the last dose of the trial drug Iin the control group without albumin until day 28 after randomisation or until discharge from the ICU, if it occurs before day 28 after randomisation. In the event that adverse events are still "ongoing" after the above dates, they were tracked until maximum the end of data collection (Day 90). If they are "ongoing" on day 90, they were documented as "not recovered," "recovered with sequelae," or "unknown.". Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Albumin Group

Serious: 3/222 (1%)

Deaths: 91/222

Control Group Without Albumin:

Serious: 2/218 (1%)

Deaths: 96/218

Serious adverse events (1 terms)

Reaction	System	Albumin Group	Control Group Without Albu…
Hypervolemia	Cardiac disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Albumin Group	Control Group Without Albu…
Sepsis related, Cardiovascular events	Vascular disorders	—	—

Most-reported serious reactions: Hypervolemia.

Data from ClinicalTrials.gov NCT03869385 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Albumin as a drug: its biological effects beyond volume expansion.
   Bihari S, Bannard-Smith J, Bellomo R. · · 2020 · cited 57× · PMID 32900333
2. Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines.
   Callum J, Skubas NJ, Bathla A, Keshavarz H, et al · · 2024 · cited 42× · PMID 38447639 · DOI 10.1016/j.chest.2024.02.049
3. Randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS): protocol for a randomized controlled trial.
   Sakr Y, Bauer M, Nierhaus A, Kluge S, et al · · 2020 · cited 28× · PMID 33287911 · DOI 10.1186/s13063-020-04921-y
4. Fluids in ARDS: more pros than cons.
   Mendes RS, Pelosi P, Schultz MJ, Rocco PRM, et al · · 2020 · cited 12× · PMID 33336259 · DOI 10.1186/s40635-020-00319-x
5. Restrictive fluid therapy and high-dose vitamin C in sepsis.
   Plummer MP, Bellomo R. · · 2022 · cited 6× · PMID 35915241 · DOI 10.1038/s41581-022-00609-5
6. Effect of albumin administration on outcomes in hypoalbuminemic patients hospitalized with community-acquired pneumonia (ALBUCAP): a prospective, randomized, phase III clinical controlled trial-a trial protocol.
   Rombauts A, Abelenda-Alonso G, Simonetti AF, Verdejo G, et al · · 2020 · cited 4× · PMID 32819439 · DOI 10.1186/s13063-020-04627-1
7. Albumin Replacement Therapy in Septic Shock: A Randomized Clinical Trial.
   Sakr Y, Nierhaus A, Schumacher U, Utzolino S, et al · · 2026 · cited 2× · PMID 41712212 · DOI 10.1001/jamanetworkopen.2025.59297
8. Management of endothelial dysfunction in septic shock: role of albumin administration.
   Martin-Loeches I, Rodríguez A, Russell L, Chew MS, et al · · 2025 · cited 1× · PMID 41310901 · DOI 10.1186/s40560-025-00836-5