Optimization of Therapeutic Human Serum Albumin Infusion in Selected Critically Ill Patients

Study Overview
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Brief Summary
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Primary purpose : mortality at Day 28 Secondary purposes : Daily SOFA (Sequential Organ Failure Assessment) score lessening within Intensive Care Unit (ICU) Duration of increasing doses of norepinephrine infusion to maintain target mean arterial pressure Number of care-related infections within ICU

Detailed Description
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According to currently available literature on therapeutic albumin infusion in critically ill patients, there is room for new approaches to delineate an optimal use of this expansive treatment. Indeed, many authors suggest that the present clinical use of albumin is questionable in critically ill patients as far as changes in morbidity or mortality are concerned and with regards to cost-effectiveness. It has been reported that protein misfolding and aggregation are a hallmark of several inflammatory diseases. In vitro studies show that very small amounts of albumin are able to restore the physiologic activities of endogenous circulating proteins that had been aggregated in multimeric form during oxidative stress. Recently, the investigators have reported that in vitro albumin restores antimicrobial and anti-inflammatory effects of some chromogranin A-derived peptides. The investigators therefore search to test in vivo, in critically ill patients with severe systemic inflammation requiring norepinephrine infusion, whether therapeutic albumin infused at a low and continuous dosage may modify mortality (primary purpose) and morbidity (secondary purposes) in comparison with intermittent high dosage albumin infusion.

Official Title
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Comparison of 2 Strategies of Therapeutic Human Serum Albumin Infusion in Critically Ill Patients With Severe Systemic Inflammatory Response Syndrome and Low Plasma Albumin: Continuous Low Versus Intermittent High Doses

Conditions
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Shock, Systemic Inflammatory Response Syndrome (SIRS), Hypoalbuminaemia

Intervention / Treatment
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* Drug: Human serum albumin infusion 4%
* Drug: Human serum albumin infusion 20%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: circulatory failure requiring norepinephrine support (any dose) hospitalization within an Intensive Care Unit SIRS low plasma albumin (< 20g/L) consent to study Exclusion Criteria: absence of circulatory failure absence of SIRS chronic low albumin concentration absence of consent to study inability to tolerate human serum albumin Patients under guardianship or curators Women pregnant

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous low dosage (CLD)<br>The subjects will received human serum albumin infusion 4%.CLD patients are infused with15ml/kg/day of 4% human serum albumin from inclusion to the day norepinephrine infusion is weaned by 30% (provided their plasma albumin stays in the range 30+3g/L) | Drug: Human serum albumin infusion 4%<br>* Continuous infusion of 15mL/kg of bodyweight over 24h/day<br>* Other names: VIALEBEX* 4%;|
| Active Comparator: Intermittent high dosage (IHD)<br>The subjects will received human serum albumin infusion 20%.IHD patients are infused with 20% human serum albumin (up to 600 ml/day) until the plasma albumin concentration is in the range 30+3g/L from inclusion to the day norepinephrine infusion is weaned by 30% | Drug: Human serum albumin infusion 20%<br>* Specify details not covered in associated Arm Description. Intermittent infusion up to 200 ml/8h/day until the plasma albumin concentration is in the range 30+3g/L<br>* Other names: VIALEBEX* 20%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 28 days after inclusion between the two groups | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The length of the circulatory failure requiring albumin infusion | Time from albumin infusion starting to the moment when norepinephrine can be weaned at least by 30% of its peak dose with respect of initial mean arterial pressure target between the two groups. | The estimated period of time will be from date of baseline visit until the date of discharge from the hospital or date of death from any cause, whichever came first, assessed up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute circulatory failure requiring norepinephrine, SIRS, Albumin, therapeutic