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

Primary Purpose

Decompensated Cirrhosis, Severe Ascites

Status
Unknown status
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Propranolol
Midodrine
Sponsored by
Institute of Liver and Biliary Sciences, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Decompensated Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institute of Liver and Biliary SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Midodrine+Propranolol

Propranolol

Arm Description

Outcomes

Primary Outcome Measures

Primary prevention of first variceal bleed in both groups
prevention of first variceal bleed is based on clinicallly

Secondary Outcome Measures

Achievement of target heart rate (THR) of 55-60 or reduction by 25 % from baseline
HVPG reduction in both groups
HVPG reduction by 20% from baseline
Survival in both groups
Incidence of therapeutic paracentesis in both groups
Incidence of therapeutic paracentesis in both groups
Incidence of decrease in ascites by at least one grade in both groups
Paracentesis induced circulatory dysfunction(PICD) in both groups
PICD is defined as Incidence of AKI and HE after paracentesis
Incidence of Hyponatremia in both groups
cut off for Hyponatremia is Sodium < 135
Episodes of bacterial infection in both groups
Bacterial infection will be identified by culture tests
Incidence of Hepatic Encephalopathy in both groups
Incidence of Hepato Renal Syndrome in both groups
Incidence of Acute Kidney Injury in both groups
Incidence of Variceal bleed in both groups
Number of TIPS (TransIntrahepatic Portosystemic Shunt) procedure done in both groups
Number of patients who will receive diuretics in both groups
Adverse effects of drugs in both groups
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

Full Information

First Posted
December 12, 2019
Last Updated
July 29, 2020
Sponsor
Institute of Liver and Biliary Sciences, India
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1. Study Identification

Unique Protocol Identification Number
NCT04208776
Brief Title
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

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 4, 2020 (Actual)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Decompensated Cirrhosis, Severe Ascites

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Midodrine+Propranolol
Arm Type
Experimental
Arm Title
Propranolol
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Propranolol
Intervention Description
maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.
Intervention Type
Drug
Intervention Name(s)
Midodrine
Intervention Description
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
Primary Outcome Measure Information:
Title
Primary prevention of first variceal bleed in both groups
Description
prevention of first variceal bleed is based on clinicallly
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Achievement of target heart rate (THR) of 55-60 or reduction by 25 % from baseline
Time Frame
Day 7
Title
HVPG reduction in both groups
Description
HVPG reduction by 20% from baseline
Time Frame
Day 90
Title
Survival in both groups
Time Frame
1 year
Title
Incidence of therapeutic paracentesis in both groups
Time Frame
Day 30
Title
Incidence of therapeutic paracentesis in both groups
Time Frame
Day 90
Title
Incidence of decrease in ascites by at least one grade in both groups
Time Frame
3 months
Title
Paracentesis induced circulatory dysfunction(PICD) in both groups
Description
PICD is defined as Incidence of AKI and HE after paracentesis
Time Frame
1 year
Title
Incidence of Hyponatremia in both groups
Description
cut off for Hyponatremia is Sodium < 135
Time Frame
1 year
Title
Episodes of bacterial infection in both groups
Description
Bacterial infection will be identified by culture tests
Time Frame
1 year
Title
Incidence of Hepatic Encephalopathy in both groups
Time Frame
1 year
Title
Incidence of Hepato Renal Syndrome in both groups
Time Frame
1 year
Title
Incidence of Acute Kidney Injury in both groups
Time Frame
1 year
Title
Incidence of Variceal bleed in both groups
Time Frame
1 year
Title
Number of TIPS (TransIntrahepatic Portosystemic Shunt) procedure done in both groups
Time Frame
1 year
Title
Number of patients who will receive diuretics in both groups
Time Frame
1 year
Title
Adverse effects of drugs in both groups
Time Frame
1 year
Title
Impact on portal, systemic and cardiac hemodynamics in both groups
Description
For Portal and cardiac HVPG and right heart pressure studies will be done and for systemic blood pressure will be measured
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dr Abhijeet Ranjan, MD
Phone
01146300000
Email
drkmrabhijeet@gmail.com
Facility Information:
Facility Name
Institute of Liver and Biliary Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr Abhijeet Ranjan, MD
Phone
01146300000
Email
drkmrabhijeet@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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