Albumin Replacement Therapy in Septic Shock

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Randomised Controlled Multicentre Study of Albumin Replacement Therapy in Septic Shock

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Albutein® 200 g/L or Plasbumin® 20


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Albumin group<br>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<br>* 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.<br>* Other names: Human Albumin 20%;|
| No Intervention: Control group without albumin:<br>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?
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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 SOFA score (range 0-24 points), with higher scores indicating higher degree of overall organ dysfunction/failure). | 28 days | 
| ICU length of stay | ICU 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human albumin, Sepsis