Fresh Frozen Plasma as a Substitute for Albumin in Patients Receiving a Large Volume Paracentesis

Large volume paracentesis (LVP) with albumin administration is the standard of care for patients with refractory ascites complicating end-stage liver disease. However, the use of albumin is frequently limited due to expense and occasional short supply. The goal of this study is to determine if the administration of Fresh Frozen Plasma (FFP) during large volume paracentesis is effective in lowering plasma renin activity by 25% compared to baseline.

Study Overview

• Status: Withdrawn
• Conditions: Liver Cirrhosis; Ascites Hepatic
• Intervention / Treatment: Biological: Fresh Frozen Plasma (FFP); Procedure: Large Volume Paracentesis (LVP); Biological: Albumin

Detailed Description

There will be three periods of this study, one for each of three consecutive routine large volume paracenteses. The length of the study will be 6 days post paracentesis for each period, for a total of 3 periods. The interval between successive LVP's will be determined by patients' need. In order to ensure follow up on Day 6, Day 1 will be restricted to a Tuesday, Wednesday, Thursday, or Friday.

All participants will be monitored for 3 consecutive routine large volume paracenteses. The 3 periods (LVP's) of this study will differ in administration of volume replacement solution. First LVP will be with intravenous albumin (12.5gm 25% Human Albumin for every 2 liters removed), 2nd LVP with administration 1 unit of FFP for every 2 liters removed for the first 4 liters followed by 12.5gm 25% albumin for every subsequent 2 liters removed, and 3rd LVP again with administration of intravenous albumin. The first LVP serves as the study entry time period and also as a control period for the same patient. The second LVP is to test the new intervention with FFP. The third LVP is included so that we can monitor the patient's status.

Albumin or FFP administration:

Albumin administration:

50ml of 25% albumin for every 2L removed

FFP administration:

2 units of FFP for the first 4L removed followed by 50ml of 25% albumin for every additional 2L removed FFP will be supplied by the Blood Bank and albumin from the pharmacy at Montefiore Medical Center.

Details for each study period:

1. st Period: Day 1: Enrollment, baseline pre-LVP laboratory testing and measurements, and large volume paracentesis with administration of albumin Day 6: Laboratory testing and measurements
2. nd Period: Day 1: pre-LVP baseline labs and measurements, LVP with FFP administration Day 6: Laboratory testing and measurements
3. rd Period: Day 1: pre-LVP baseline labs and measurements, LVP with albumin administration Day 6: Laboratory testing and measurements

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years or older
2. Cirrhosis of the liver based on biopsy or clinical and radiographic criteria
3. Ability to provide informed consent (Grade 0 to 1 HE)
4. Grade 3 ascites or refractory ascites
5. Ascites requiring frequent large volume paracentesis of at least 5 liters at least once a month
6. No diuretic use
7. INR > 1.7, <2.5

Exclusion Criteria:

1. Inability to obtain informed consent
2. Age less than 18
3. Hepatic Encephalopathy Grade > 1 as defined by the presence of an impaired mental status or the presence of asterixis
4. Septic shock
5. Active infection
6. Respiratory failure
7. Heart failure with reduced ejection fraction of ≤ 50%
8. Moderate or severe pulmonary hypertension
9. History of stroke
10. Unstable coronary artery disease
11. Chronic kidney disease (GFR <60)
12. GI bleed within 2 weeks
13. Any licorice within 2 weeks of starting the study
14. Any Beta Blocker use within the last 2 weeks
15. Any diuretic use within 2 weeks
16. Absence of paracentesis within 2 weeks
17. Absence of volume expanders within 2 weeks
18. INR > 1.7
19. Pregnancy - pregnancy test will be administered for all female patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Large Volume Paracentesis (LVP) with Fresh Frozen Plasma (FFP); All participants who are scheduled for a LVP and meet the eligibility criteria will be monitored for 3 consecutive periods. At the second drainage participants will receive 2 units, or about 500 ccs, of fresh frozen plasma intravenously, plus 1 bottle, or 50 ccs, of 25% albumin if more than 4 liters of fluid are removed	Biological: Fresh Frozen Plasma (FFP); FFP will be used as a substitute for albumin during the 2nd of 3 total paracentesis being monitored; Procedure: Large Volume Paracentesis (LVP); All participants who have this procedure, meet eligibility criteria and who consent
Active Comparator: Large Volume Paracentesis (LVP) with Albumin; All participants who are scheduled for a LVP and meet the eligibility criteria will be monitored for 3 consecutive periods. At the first and third drainage participants will receive 1 bottle, or 50 ccs, of 25% albumin intravenously for every two liters of fluid removed	Procedure: Large Volume Paracentesis (LVP); All participants who have this procedure, meet eligibility criteria and who consent; Biological: Albumin; Albumin will be used during the 1st and 3rd paracentesis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma renin activity (PRA) post paracentesis	Efficacy of LVP with FFP will be measured as the change of plasma renin activity (PRA) from Day 1 to Day 6 during the 2nd LVP with FFP. We hypothesize that FFP will reduce the PRA by 25% from Day 1 to Day 6.	6 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of post-paracentesis circulatory dysfunction (PPCD)	We hypothesize that the PPCD incidence will reduce in the 2nd LVP with FFP in comparison to the 1st LVP with albumin.	6 days
Safety: Adverse Events (AE)	We hypothesize that the overall adverse events (including PPCD incidence) will be reduced in the 2nd LVP with FFP in comparison to the 1st LVP with albumin. AE's will be summarized by presenting the number and percentages of patients having any AE.	6 days

Collaborators and Investigators

• Sponsor: Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Plasma; Paracentesis; Albumin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites
• Other Study ID Numbers: 2019-10354

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data collected during the study will only be shared with researchers that have been IRB approved as key-personnel on the study protocol.

Drug and device information, study documents

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