Effect of Albumin Administration on Vasopressor Duration in Resolving Septic Shock

Study Overview
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Brief Summary
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The role of albumin in sepsis has been controversial for decades. Although hypoalbuminemia has been associated with worse outcomes in sepsis, definitive evidence does not exist that replacing albumin in these patients improves outcomes. However, subgroup analyses from large clinical trials indicate that albumin may reduce mortality in septic shock, and in particular, may reduce the time a patient requires vasopressor support. Given this background, we are conducting this study to evaluate the role of albumin replacement in the patient with resolving septic shock to determine if albumin administration reduces the time a patient requires vasopressor support, reduces the time required for central line, and ultimately whether any potential benefit in terms of reduction of vasopressor support is associated with ICU length of stay and other outcomes. The approach is unique from larger trials of albumin in that it is a septic shock study geared at a particular phenotype of the patient in septic shock and evaluating a specific intervention at a specific time point in the course of septic shock.

Official Title
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Effect of Albumin Administration on Vasopressor Duration in Resolving Septic Shock

Conditions
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Shock, Septic

Intervention / Treatment
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* Drug: 25% Albumin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older who meet the clinical criteria for septic shock a. Presence of two or more of the following: i. A core temp ≥38C or ≤36C; ii. A heart rate ≥90 beats/min; iii. A respiratory rate ≥ 20 breaths/min or PaCO2 ≤32mmHg or use of mechanical ventilation for an acute process; iv. A white blood cell count ≥12000/ml or ≤4000/ml or immature neutrophils > 10%. b. Presence of defined (or suspected) site of infection as show by at least one of the following criteria: i. An organism grown in blood or sterile site; ii. An abscess or portion of infected tissue; iii. Suspected infection despite culture growth by the attending physician. c. Infusion of vasopressors is required to maintain blood pressure Vasopressor requirements a. Patients can be considered for study inclusion when his/her vasopressor requirements are as follows: i. Norepinephrine 0.04-0.25 mcg/kg/min (plus or minus vasopressin) OR phenylephrine 0.2-2 mcg/kg/min (plus or minus vasopressin) AND ii. Last measured lactate value was < 4 mmol/L AND iii. The patient is on stable or decreasing doses of vasopressors for 8 hours or more. This 8 hour measurement will start at the maximum amount of vasopressor support within the range defined in i. above. Serum albumin level <2.5g/dl. The level must be drawn within the last 24 hours of Time=0. Exclusion Criteria: Patients <18 years old Albumin administration 24 hours prior to the time of enrollment (Time=0) Prisoners Terminal state Known adverse reaction to albumin administration Pregnancy Pathological conditions in which albumin administration is clinically indicated (hepatic cirrhosis with ascites, hepatorenal syndrome, intestinal malabsorption syndrome, nephrotic syndrome, burns) Patients with acute liver failure or cirrhosis Patients on continuous renal replacement therapy Patients who are morbidly obese ≥40kg/m2 Religious objection to the administration of human blood products.

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25% Albumin<br>25% albumin 75 grams IV over 1 hour once. | Drug: 25% Albumin<br> <br> |
| Placebo Comparator: Placebo<br>0.9% normal saline 200mL IV over 1 hour once. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Cessation of Vasopressor Therapy | Time from study drug administration to when the patient no longer requires vasopressor support | Until ICU Discharge (up to 28 days after study drug administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Central Line Discontinuation | Time from study drug administration to discontinuation of a patient's central line | Until ICU Discharge (up to 28 days after study drug administration) | 
| Time on Mechanical Ventilation | Time the patient requires mechanical ventilation during their ICU stay | Until ICU Discharge (up to 28 days after study drug administration) | 
| ICU Mortality |  | Until ICU Discharge (up to 28 days after study drug administration) | 
| ICU Length of Stay | How long the patient is in the intensive care unit | Until ICU Discharge (up to 28 days after study drug administration) | 
| Central venous pressure | The central venous pressure (in mm Hg) will be measured hourly from a central line until 24 hours following study drug administration. | Measured hourly until 24 hours following study drug administration | 
| Heart Rate | The heart rate will be measured hourly until 24 hours following study drug administration. | Measured hourly until 24 hours following study drug administration | 
| Mean arterial pressure | The mean arterial pressure (in mm Hg) will be measured hourly from an arterial line until 24 hours following study drug administration. | Measured hourly until 24 hours following study drug administration | 
| Serum creatinine | Serum creatinine will be measured with AM labs the day following study drug administration and compared with baseline. | Measured the day following study drug administration | 
| Urine output | Urine output (in mL) will be measured as part of routine care and totaled for the 24 hour urine output since study drug administration. | Measured for 24 hours following study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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albumin, septic shock