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

Not Applicable

Completed

• Conditions: Decompensated Cirrhosis; Severe Ascites
• Interventions: Drug: Propranolol; Drug: Midodrine

• Registration Number: NCT04208776
• Lead Sponsor: Institute of Liver and Biliary Sciences, India

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-12
• Study First Submitted QC: 2019-12-19
• Study First Posted: 2019-12-23
• Study Start: 2020-02-04
• Primary Completion: 2021-12-31
• Study Completion: 2021-12-31
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-19
• Last Update Posted: 2024-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Midodrine+Propranolol	Propranolol	-
Midodrine+Propranolol	Midodrine	-
Propranolol	Propranolol	-

Primary Outcome Measures

Name	Time	Method
Primary prevention of first variceal bleed in both groups	1 year	prevention of first variceal bleed is based on clinicallly

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Institute of Liver and Biliary Sciences; 🇮🇳 New Delhi, Delhi, India