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

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ClinicalTrials.gov Identifier: NCT04208776
Recruitment Status : Recruiting
First Posted : December 23, 2019
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Decompensated Cirrhosis Severe Ascites Drug: Propranolol Drug: Midodrine Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Combination of Midodrine With Propranolol in Preventing First Bleed in Decompensated Cirrhotics With Severe Ascites: A Randomized Controlled Trial"
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: Midodrine+Propranolol Drug: Propranolol
maximum tolerated dose of propranolol with initial dosage of 20mg once a day and uptitrating every 2nd day by 20 mg.

Drug: 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

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




Primary Outcome Measures :
  1. Primary prevention of first variceal bleed in both groups [ Time Frame: 1 year ]
    prevention of first variceal bleed is based on clinicallly


Secondary Outcome Measures :
  1. Achievement of target heart rate (THR) of 55-60 or reduction by 25 % from baseline [ Time Frame: Day 7 ]
  2. HVPG reduction in both groups [ Time Frame: Day 90 ]
    HVPG reduction by 20% from baseline

  3. Survival in both groups [ Time Frame: 1 year ]
  4. Incidence of therapeutic paracentesis in both groups [ Time Frame: Day 30 ]
  5. Incidence of therapeutic paracentesis in both groups [ Time Frame: Day 90 ]
  6. Incidence of decrease in ascites by at least one grade in both groups [ Time Frame: 3 months ]
  7. Paracentesis induced circulatory dysfunction(PICD) in both groups [ Time Frame: 1 year ]
    PICD is defined as Incidence of AKI and HE after paracentesis

  8. Incidence of Hyponatremia in both groups [ Time Frame: 1 year ]
    cut off for Hyponatremia is Sodium < 135

  9. Episodes of bacterial infection in both groups [ Time Frame: 1 year ]
    Bacterial infection will be identified by culture tests

  10. Incidence of Hepatic Encephalopathy in both groups [ Time Frame: 1 year ]
  11. Incidence of Hepato Renal Syndrome in both groups [ Time Frame: 1 year ]
  12. Incidence of Acute Kidney Injury in both groups [ Time Frame: 1 year ]
  13. Incidence of Variceal bleed in both groups [ Time Frame: 1 year ]
  14. Number of TIPS (TransIntrahepatic Portosystemic Shunt) procedure done in both groups [ Time Frame: 1 year ]
  15. Number of patients who will receive diuretics in both groups [ Time Frame: 1 year ]
  16. Adverse effects of drugs in both groups [ Time Frame: 1 year ]
  17. Impact on portal, systemic and cardiac hemodynamics in both groups [ Time Frame: 1 year ]
    For Portal and cardiac HVPG and right heart pressure studies will be done and for systemic blood pressure will be measured



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04208776


Contacts
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Contact: Dr Abhijeet Ranjan, MD 01146300000 drkmrabhijeet@gmail.com

Locations
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India
Institute of Liver and Biliary Sciences Recruiting
New Delhi, Delhi, India, 110070
Contact: Dr Abhijeet Ranjan, MD    01146300000    drkmrabhijeet@gmail.com   
Sponsors and Collaborators
Institute of Liver and Biliary Sciences, India
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Responsible Party: Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier: NCT04208776    
Other Study ID Numbers: ILBS-Cirrhosis-27
First Posted: December 23, 2019    Key Record Dates
Last Update Posted: February 24, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ascites
Pathologic Processes
Propranolol
Midodrine
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists