Effect of Albumin Administration on Vasopressor Duration in Resolving Septic Shock

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.

Study Overview

• Status: Terminated
• Conditions: Shock, Septic
• Intervention / Treatment: Drug: Placebo; Drug: 25% Albumin

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky HealthCare Chandler Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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

2. 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.

3. Serum albumin level <2.5g/dl. The level must be drawn within the last 24 hours of Time=0.

Exclusion Criteria:

1. Patients <18 years old
2. Albumin administration 24 hours prior to the time of enrollment (Time=0)
3. Prisoners
4. Terminal state
5. Known adverse reaction to albumin administration
6. Pregnancy
7. Pathological conditions in which albumin administration is clinically indicated (hepatic cirrhosis with ascites, hepatorenal syndrome, intestinal malabsorption syndrome, nephrotic syndrome, burns)
8. Patients with acute liver failure or cirrhosis
9. Patients on continuous renal replacement therapy
10. Patients who are morbidly obese ≥40kg/m2
11. Religious objection to the administration of human blood products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexander Flannery, 859-323-4011
• Investigators: Principal Investigator: Alexander H. Flannery, Pharm.D., University of Kentucky

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: February 19, 2016
• First Submitted That Met QC Criteria: March 17, 2016
• First Posted (Estimate): March 23, 2016

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: albumin, septic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 14-0727-F2L

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: No