Efficacy of Albumin Plus Midodrine v/s Albumin Alone in Reducing Incidence of Paracentesis Induced Circulatory Dysfunctions in ACLF Patients.

Efficacy of Albumin Plus Midodrine v/s Albumin Alone in Reducing Incidence of Paracentesis Induced Circulatory Dysfunctions in ACLF Patients-A Randomized Controlled Trial.

The patients with ACLF having Ascites who require ascitic tapping will undergone ascitic tapeither under albumin cover alone or with midodrine. The patient will be monitored for complication and changes of PICD. Study analysis will be done with primary objective being reduction in incidence of PICD.

Study Overview

• Status: Unknown
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Other: Placebo; Biological: Albumin; Drug: Midodrine Oral Tablet

Detailed Description

OBJECTIVE:

Primary objective: Incidence of Paracentesis induced circulatory dysfunction in patients undergoing modest volume paracentesis (MVP) (>3 and <5 litres) with midodrine plus 25% albumin v/s 25% albumin infusion alone at day 7

Secondary objective:

• Change in systolic, diastolic and mean BP at day 3 and 6
• Increase in plasma renin activity at day 6
• Incidence of Hyponatremia, HE and AKI at day 3 and 6
• Predictors of Paracentesis induced circulatory dysfunction
• Predictors of 28 day survival.

Methodology :

Patients with Acute on chronic liver failure having grade III ascites will be given either albumin or albumin plus midodrine. Midodrine will be started 4 hrs before tap to achieve target MAP. Ascitic tapping will be followed by vital monitoring and monitoring of vital parameters along with measurement of changes in s. rennin at day 3 and 6.

• All patient will be undergo complete physical examination and complete clinical history will be recorded.
• Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin levels
• Those eligible will be randomised in to two groups
• GROUP A will be given albumin 8g/l of ascitic tap during tap along with placebo for 7 days.
• GROUP B will be given midodrine 7.5 mg to 12.5 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group.

Study Population: Patients of acute on chronic liver failure who are admitted to and attending the OPD at ILBS.

Study Design: Randomized controlled trial Study Period:NOV 2019 to march 2019

Sample Size:

Considering incidence of PICD in albumin group is 30% and reduction to 10% by adding midodrine with alpha =5%, and power of study being 80%. No. of cases in each group- 66 Total-132 Furthur with 10% dropout we need to enroll 150 cases (75 in each group) randomly allocated in two groups by block randomization method with block size of 5.

• Intervention: This RCT will be conducted at ILBS New Delhi between Dec 2019 and March 2021
• Monitoring and assessment:
• All patient will be undergo complete physical examination and complete clinical history will be recorded.
• Baseline cbc,LFT,KFT and INR level will be sent on day 1 along with baseline s. renin levels
• Those eligible will be randomised in to two groups
• GROUP A will be given albumin 8g/l of ascitic tap along with placebo for 7 days. Standard albumin therapy will continue (40gm/week)
• GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group.

Expected outcome of the project:

Primary:

• Incidence of PICD at day 3 and day6

Secondary:

• Changes in hemodynamic parameters at 1, 3 and 6 hour, Day 3, Day 6 post paracentesis
• Increase in plasma renin activity at Day 3, Day 6
• Incidence of Hyponatremia, HE and AKI at day 3 and 6

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- ACLF patients (as per APASL definition) with grade II/III ascites

Exclusion Criteria:

1. Age < 18 or >75 years
2. Hepatocellular carcinoma
3. Extrahepatic portal vein obstruction
4. Non cirrhotic ascites
5. Serum creatinine >1.5mg/dl
6. Refractory septic shock
7. Beta blockersPortal vein thrombosis
8. Grade 3-4 HE
9. Pregnancy or Lactation
10. Active variceal bleed
11. Respiratory, cardiac, renal failure
12. Uncontrolled hypertension
13. Severe coagulopathy
14. Refusal to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Albumin with placebo; Group A will be given albumin 8g/l of ascitic tap along with placebo for 7 days. Standard albumin therapy will continue (40gm/week)	Other: Placebo; Placebo; Biological: Albumin; Albumin will be 8g/l of ascitic tap. Standard albumin therapy will continue (40gm/week)
EXPERIMENTAL: Albumin with Midodrine; GROUP B will be given midodrine 7.5 mg to 10 mg tds (keeping the target MAP above 70 mmhg)for 7 days plus albumin same as in other group.	Biological: Albumin; Albumin will be 8g/l of ascitic tap. Standard albumin therapy will continue (40gm/week); Drug: Midodrine Oral Tablet; Midodrine 7.5 mg to 10 mg TDS (keeping the target MAP above 70 mmHg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of PICD (Paracentesis Induced Circulatory Dysfunction)	Day 3
Incidence of PICD (Paracentesis Induced Circulatory Dysfunction)	Day 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in Mean Arterial Pressure (MAP) post paracentesis.	1 hour
Changes in Heart Rate post paracentesis.	1 hour
Changes in Mean Arterial Pressure (MAP) post paracentesis.	3 hours
Changes in Heart Rate post paracentesis.	3 hours
Changes in Mean Arterial Pressure (MAP) post paracentesis.	6 hours
Changes in Heart Rate post paracentesis.	6 hours
Changes in Mean Arterial Pressure (MAP) post paracentesis.	Day 3
Changes in Heart Rate post paracentesis.	Day 3
Changes in Mean Arterial Pressure (MAP) post paracentesis.	Day 6
Changes in Heart Rate post paracentesis.	Day 6
Change in plasma renin activity in both groups	Day 3
Change in plasma renin activity in both groups	Day 6
Incidence of Hyponatremia in both groups	Day 3
Incidence of Hyponatremia in both groups	Day 6
Incidence of Hepatic Encephalopathy in both groups	Day 3
Incidence of Hepatic Encephalopathy in both groups	Day 6
Incidence of Acute Kidney Injury in both groups	Day 3
Incidence of Acute Kidney Injury in both groups	Day 6

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 15, 2020
• Primary Completion (ANTICIPATED): March 31, 2021
• Study Completion (ANTICIPATED): March 31, 2021

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 13, 2020
• First Posted (ACTUAL): July 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 16, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Acute-On-Chronic Liver Failure; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Midodrine
• Other Study ID Numbers: ILBS-ACLF-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No