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

Decompensated Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04208776
• Other study ID #: ILBS-Cirrhosis-27
• Status: Completed
• Phase: N/A
• Start date: February 4, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2024
• Source: Institute of Liver and Biliary Sciences, India
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ascites
• Decompensated Cirrhosis
• Severe Ascites

Intervention

Drug:
• Propranolol
maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.
• 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

Locations

Country	Name	City	State
India	Institute of Liver and Biliary Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary prevention of first variceal bleed in both groups	prevention of first variceal bleed is based on clinicallly	1 year
Secondary	Achievement of target heart rate (THR) of 55-60 or reduction by 25 % from baseline		Day 7
Secondary	HVPG reduction in both groups	HVPG reduction by 20% from baseline	Day 90
Secondary	Survival in both groups		1 year
Secondary	Incidence of therapeutic paracentesis in both groups		Day 30
Secondary	Incidence of therapeutic paracentesis in both groups		Day 90
Secondary	Incidence of decrease in ascites by at least one grade in both groups		3 months
Secondary	Paracentesis induced circulatory dysfunction(PICD) in both groups	PICD is defined as Incidence of AKI and HE after paracentesis	1 year
Secondary	Incidence of Hyponatremia in both groups	cut off for Hyponatremia is Sodium < 135	1 year
Secondary	Episodes of bacterial infection in both groups	Bacterial infection will be identified by culture tests	1 year
Secondary	Incidence of Hepatic Encephalopathy in both groups		1 year
Secondary	Incidence of Hepato Renal Syndrome in both groups		1 year
Secondary	Incidence of Acute Kidney Injury in both groups		1 year
Secondary	Incidence of Variceal bleed in both groups		1 year
Secondary	Number of TIPS (TransIntrahepatic Portosystemic Shunt) procedure done in both groups		1 year
Secondary	Number of patients who will receive diuretics in both groups		1 year
Secondary	Adverse effects of drugs in both groups		1 year
Secondary	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