Clinical trial NCT04208776: Efficacy of Combination of Midodrine With Propranolol in Preventing First Bleed in Decompensated Cirrhotics With Severe Ascites.
Official title: Efficacy of Combination of Midodrine With Propranolol in Preventing First Bleed in Decompensated Cirrhotics With Severe Ascites: A Randomized Controlled Trial"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Decompensated Cirrhosis
Severe Ascites
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2019-12-23
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Primary prevention of first variceal bleed in both groups
timeFrame: 1 year
Secondary outcomes:
measure: Achievement of target heart rate (THR) of 55-60 or reduction by 25 % from baseline
timeFrame: Day 7
measure: HVPG reduction in both groups
timeFrame: Day 90
measure: Survival in both groups
timeFrame: 1 year
measure: Incidence of therapeutic paracentesis in both groups
timeFrame: Day 30
measure: Incidence of therapeutic paracentesis in both groups
timeFrame: Day 90
measure: Incidence of decrease in ascites by at least one grade in both groups
timeFrame: 3 months
measure: Paracentesis induced circulatory dysfunction(PICD) in both groups
timeFrame: 1 year
measure: Incidence of Hyponatremia in both groups
timeFrame: 1 year
measure: Episodes of bacterial infection in both groups
timeFrame: 1 year
measure: Incidence of Hepatic Encephalopathy in both groups
timeFrame: 1 year
measure: Incidence of Hepato Renal Syndrome in both groups
timeFrame: 1 year
measure: Incidence of Acute Kidney Injury in both groups
timeFrame: 1 year
measure: Incidence of Variceal bleed in both groups
timeFrame: 1 year
measure: Number of TIPS (TransIntrahepatic Portosystemic Shunt) procedure done in both groups
timeFrame: 1 year
measure: Number of patients who will receive diuretics in both groups
timeFrame: 1 year
measure: Adverse effects of drugs in both groups
timeFrame: 1 year
measure: Impact on portal, systemic and cardiac hemodynamics in both groups
timeFrame: 1 year
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver and Biliary Sciences
state: Delhi
Study officials:
References: