Efficacy of Combination of Midodrine With Propranolol in Preventing First Bleed in Decompensated Cirrhotics With Severe Ascites.

Efficacy of Combination of Midodrine With Propranolol in Preventing First Bleed in Decompensated Cirrhotics With Severe Ascites: A Randomized Controlled Trial"

Study population: Decompensated cirrhotics requiring primary prophylaxis with asciteswho are admitted to and attending the OPD at ILBS.

Study Design : A Randomized controlled trial Study period : August 2019 to December 2020 (1.5 Years) Intervention : Treatment naïve patients will be given Propranolol and dose will be titrated every 2ndday to attain a target heart rate of 55.

One group patients will be given maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.The patients who bleed will undergo EVL session.

To the other group Midodine will be added to Propranolol.It will be started at 2.5mg TDS and will be uptitrated every 2nd day to a max of 10mg TDS to attain a MAP of atleast 70mm Hg and then uptitate the beta blocker simulataneously to attain the target heart rate. The patients who bleed will undergo EVL session.

Monitoring and assessment :

The patient will be monitored every day. The patient will undergo physical examination, complete blood counts, at baseline, LFT, KFT, at every 2nd day and day 7 from the start of therapy.

Adverse effects : Bradycardia and hypotension due to beta blockers Stopping rule : Severe hyponatraemia (<125), low mean arterial pressure(<65) or cardiac output and increasing serum creatinine(>1.5) identifies more vulnerable patients among those with decompensated cirrhosis, in whom a dose reduction or temporal discontinuation of NSBB treatment will be considered.

Study Overview

• Status: Completed
• Conditions: Decompensated Cirrhosis; Severe Ascites
• Intervention / Treatment: Drug: Propranolol; Drug: Midodrine

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Decompensated Child C cirrhotics with grade II-III requiring primary prophylaxis

Exclusion Criteria:

1. Spontaneous bacterial peritonitis
2. Hepatic Encephalopathy
3. Acute renal failure (S.Cr>1.5)
4. Hepatorenal syndrome
5. Hypertension
6. Coronary Artery Disease ; H/o arrhythmias, heart block
7. Urinary retention
8. Pheochromocytoma/thyrotoxicosis
9. Coronary Obstructive Pulmonary Disease
10. Hepatocellular Carcinoma
11. Pregnancy
12. Portal vein Thrombosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propranolol	Drug: Propranolol; maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.
Experimental: Midodrine+Propranolol	Drug: Propranolol; maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.; Drug: Midodrine; It will be started at 2.5mg TDS and will be uptitrated every 2nd day to a max of 10mg TDS to attain a MAP of atleast 70mm Hg and then uptitate the beta blocker simulataneously to attain the target heart rate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary prevention of first variceal bleed in both groups	prevention of first variceal bleed is based on clinicallly	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of target heart rate (THR) of 55-60 or reduction by 25 % from baseline		Day 7
HVPG reduction in both groups	HVPG reduction by 20% from baseline	Day 90
Survival in both groups		1 year
Incidence of therapeutic paracentesis in both groups		Day 30
Incidence of therapeutic paracentesis in both groups		Day 90
Incidence of decrease in ascites by at least one grade in both groups		3 months
Paracentesis induced circulatory dysfunction(PICD) in both groups	PICD is defined as Incidence of AKI and HE after paracentesis	1 year
Incidence of Hyponatremia in both groups	cut off for Hyponatremia is Sodium < 135	1 year
Episodes of bacterial infection in both groups	Bacterial infection will be identified by culture tests	1 year
Incidence of Hepatic Encephalopathy in both groups		1 year
Incidence of Hepato Renal Syndrome in both groups		1 year
Incidence of Acute Kidney Injury in both groups		1 year
Incidence of Variceal bleed in both groups		1 year
Number of TIPS (TransIntrahepatic Portosystemic Shunt) procedure done in both groups		1 year
Number of patients who will receive diuretics in both groups		1 year
Adverse effects of drugs in both groups		1 year
Impact on portal, systemic and cardiac hemodynamics in both groups	For Portal and cardiac HVPG and right heart pressure studies will be done and for systemic blood pressure will be measured	1 year

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ascites; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Adrenergic alpha-1 Receptor Agonists; Propranolol; Midodrine
• Other Study ID Numbers: ILBS-Cirrhosis-27

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