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

Study Overview
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Brief Summary
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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.

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

Conditions
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Decompensated Cirrhosis, Severe Ascites

Intervention / Treatment
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* Drug: Propranolol
* Drug: Midodrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Decompensated Child C cirrhotics with grade II-III requiring primary prophylaxis Exclusion Criteria: Spontaneous bacterial peritonitis Hepatic Encephalopathy Acute renal failure (S.Cr>1.5) Hepatorenal syndrome Hypertension Coronary Artery Disease ; H/o arrhythmias, heart block Urinary retention Pheochromocytoma/thyrotoxicosis Coronary Obstructive Pulmonary Disease Hepatocellular Carcinoma Pregnancy Portal vein Thrombosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midodrine+Propranolol<br> | Drug: Propranolol<br>* maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.<br>Drug: Midodrine<br>* 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<br>|
| Active Comparator: Propranolol<br> | Drug: Propranolol<br>* maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.<br>|

What is the study measuring?
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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 |