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

Phase 2

Withdrawn

• Conditions: Liver Cirrhosis; Ascites Hepatic
• Interventions: Biological: Fresh Frozen Plasma (FFP); Biological: Albumin; Procedure: Large Volume Paracentesis (LVP)

• Registration Number: NCT04109144
• Lead Sponsor: Montefiore Medical Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-09-25
• Study First Submitted QC: 2019-09-27
• Study First Posted: 2019-09-30
• Study Start: 2019-11-11
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-22
• Last Update Posted: 2022-08-25
• Primary Completion: 2023-07
• Study Completion: 2023-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Large Volume Paracentesis (LVP) with Albumin	Large Volume Paracentesis (LVP)	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
Large Volume Paracentesis (LVP) with Fresh Frozen Plasma (FFP)	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
Large Volume Paracentesis (LVP) with Fresh Frozen Plasma (FFP)	Large Volume Paracentesis (LVP)	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
Large Volume Paracentesis (LVP) with Albumin	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

Primary Outcome Measures

Name	Time	Method
Change in plasma renin activity (PRA) post paracentesis	6 Days	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.

Secondary Outcome Measures

Name	Time	Method
Occurrence of post-paracentesis circulatory dysfunction (PPCD)	6 days	We hypothesize that the PPCD incidence will reduce in the 2nd LVP with FFP in comparison to the 1st LVP with albumin.
Safety: Adverse Events (AE)	6 days	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.