- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06041932
Pentoxifylline Plus Carvedilol vs Carvedilol Monotherapy in Preventing New Decompensation in Stable Cirrhotic Patients With Prior Decompensation
Pentoxifylline Plus Carvedilol vs Carvedilol Monotherapy in Preventing New Decompensation in Stable Cirrhotic Patients With Prior Decompensation, an Open Label Randomised Control Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
- Study population: Cirrhotic patients with prior decompensation at least 3 months ago
- Study design: A Open label randomized controlled trial
- Sample size Assuming decompensation in Arm 1 as 25%, and 10% in Arm 2, alpha error- 5, power - 80, 160 patients, 10 % lost to follow up - 180, Each arm 90 patients.
- Intervention Arm 1 : Carvedilol Arm 2 : Pentoxiphylline plus Carvedilol
- Monitoring and assessment
At enrollment:
- - Complete history and physical examination
- Prior ascites, Hepatic encephalopathy, acute variceal bleed.
- Time to prior decompensation
- Pattern and number of prior decompensation
- Prior spontaneous bacterial peritonitis, hydrothorax, Acute on chronic liver failure, acute kidney injury
- Use of Non selective beta blockers, norfloxaxin, rifaximin and albumin
- Recent herbal/drugs intake
- History of EVL or other endotherapy
- History of hypertension, diabetes mellitus
- Fever , signs of sepsis
- Examination- Sarcopenia, fraility, icterus, pedal edema
At follow-up (at 3 month, 6 month, 9 month, 12 month): Physical (preferably)
• Complete history and physical examination
- New onset ascites, Hepatic encephalopathy, acute variceal bleed, clinical Jaundice
- Time to new decompensation from enrollment
- Pattern and number of new decompensation
- Other complications - Spontaneous bacterial peritonitis, hydrothorax, Acute on chronic liver failure, acute kidney injury.
- Recent herbal/drugs intake
- History of EVL or other endotherapy
- Hypertension, Diabetes control
- Fever , signs of sepsis
- Examination- Sarcopenia, fraility, icterus, pedal edema, ascites, Hepatic encephalopathy
Clinical evaluation
- Etiology of chronic liver disease (Baseline)
- Control of etiological factor (Baseline, 3 monthly) Alcohol - No relapse, if relapse - severity HBV - on antivirals, HBV DNA -ve HCV - HCV RNA -ve Metabolic risk factors control- DM, HT, weight etc.
- Severity of liver disease (Baseline, 3 monthly) MELD score, MELD-Na score, CTP score
- Complications (at 3 month, 6 month, 9 month, 12 month):
Overt Hepatic Encephalopathy, Portal hypertension related bleed, clinical jaundice, ascites, hyponatremia, Acute kidney injury, spontaneous bacterial peritonitis, Infections
Laboratory parametres
- Baseline (at enrollment) - Blood : KFT, LFT, CBC, INR, AFP, TNF-a, IL-6, CRP, VWF, ADAM TS 13 Imaging : USG abdomen, LSM, SSM, ECHO Hemodynamics : HVPG (not mandatory)
- At 3 and 6 month - Blood : KFT, LFT, CBC, INR Imaging : USG abdomen, LSM, SSM
At 1 year (end of follow-up) Blood : KFT, LFT, CBC, INR, AFP, TNF-a, IL-6, CRP, VWF, ADAM TS 13 Imaging : USG abdomen, LSM, SSM Hemodynamics : HVPG ( not mandatory)
- STATISTICAL ANALYSIS:
- Data will be reported as mean + SD.
- Categorical variables will be compared using the chi-square test or Fisher exact test
- Normal continuous variables will be compared using the Student's t test
- Non normal continuous variables will be compared using the Mann-Whitney rank-sum test (unpaired data) or the Wilcoxon test (paired data).
- The actuarial probability of survival will be calculated by the Kaplan-Meier method and compared using the log-rank test.
- A Cox regression analysis will be performed to identify independent prognostic factors for survival.
- Univariate and multivariate analysis will be used whenever applicable. - Adverse effects Carvedilol - Bradycardia, hypotension, giddiness, diarrhea, insomnia, hyperglycemia, weight gain, increased BUN, increased nonprotein nitrogen (NPN), increased cough, abnormal vision.
Pentoxiphylline - Abdominal discomfort, bloating, diarrhea, Dizziness, headache, flushing, chest pain, arrhythmias, hypertension, dyspnea, tachycardia, and hypotension.
- Stopping rule If primary end point achieved or any adverse event due to drug
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Dr Jaifrin Daniel, MD
- Phone Number: 01146300000
- Email: jdaniel.m07@gmail.com
Study Locations
-
-
Delhi
-
New Delhi, Delhi, India, 110070
- Institute of Liver & Biliary Sciences.
-
Contact:
- Dr Jaifrin Daniel, MD
- Phone Number: +91-011-46300000
- Email: jdaniel.m07@gmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 18-70 years
- Cirrhosis with prior clinical decompensation (ascites, Hepatic encephalopathy, Portal Hypertension related bleed)
- No current clinical decompensation (for at least 3 months)
Exclusion Criteria:
- Post TIPS/ BRTO/ SAE patients
- Post renal or liver transplantation
- History of CAD, ischemic cardiomyopathy, PVD, ventricular arrythmia
- Presence of clinical ascites, HE, Jaundice
- Last clinical decompensation within 3 months.
- Ongoing significant alcohol use
- Active HCV/HBV infection (Detectable HCV RNA/ HBV DNA)
- Prior Intolerance to carvedilol and hypersensitivity to Pentoxyfylline
- Use of Pentoxifylline within last 1 month
- AIH/PBC
- Lack of informed consent
- Hepatocellular carcinoma / Portal vein thrombosis/ Budd Chiari Syndrome
- Non-cirrhotic portal hypertension
- Ongoing CAM/Hepatotoxic drug intake
- Known HIV infection
- Pregnant women
- HepatoPulmonary Syndrome
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pentoxiphylline plus Carvedilol
|
Carvedilol
Pentoxiphylline
|
Active Comparator: Carvedilol
PCarvedilol
|
Carvedilol
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of New onset clinical decompensation (any of overt HE, variceal bleed, clinical jaundice and ascites) at 1 year in two groups.
Time Frame: 1 year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality at 6 months
Time Frame: 6 months
|
6 months
|
|
Precipitants, timing of new-onset decompensation at 6 months in two groups.
Time Frame: 6 months
|
6 months
|
|
Precipitants, timing of new-onset decompensation at 12 months in two groups
Time Frame: 12 months
|
12 months
|
|
Mortality at 12 months in two groups.
Time Frame: 12 months
|
12 months
|
|
Changes in Liver stiffness measured by Fibroscan at 6 months
Time Frame: 6 months
|
6 months
|
|
Changes in Liver stiffness measured by Fibroscan at 12 months
Time Frame: 12 months
|
12 months
|
|
Change in ESR at 6 months in both groups
Time Frame: 6 months
|
6 months
|
|
Change in CRP at 6 months in both groups
Time Frame: 6 months
|
6 months
|
|
Change in IL 6 at 6 months in both groups
Time Frame: 6 months
|
6 months
|
|
Change in TNF Alpha at 6 months in both groups
Time Frame: 6 months
|
6 months
|
|
Change in Von Willebrand factor at 6 months in both groups
Time Frame: 6 months
|
6 months
|
|
Change in ADAM TS 13 at 6 months in both groups
Time Frame: 6 months
|
6 months
|
|
Change in ESR at 12 months in both groups.
Time Frame: 12 months
|
12 months
|
|
Change in CRP at 12 months in both groups
Time Frame: 12 months
|
12 months
|
|
Change in IL 6 at 12 months in both groups
Time Frame: 12 months
|
12 months
|
|
Change in TNF Alpha at 12 months in both groups
Time Frame: 12 months
|
12 months
|
|
Change in Von Willebrand factor at 12 months in both groups
Time Frame: 12 months
|
12 months
|
|
Change in ADAM TS 13 at 12 months in both groups
Time Frame: 12 months
|
12 months
|
|
Dose of Pentoxifylline and Carvedilol at 6 months.
Time Frame: 6 months
|
6 months
|
|
Dose of Pentoxifylline and Carvedilol at 12 months
Time Frame: 12 months
|
12 months
|
|
Number of patients with change in CTP in both groups.
Time Frame: 3 month, 6 month, 9 month and at end of 1 year
|
3 month, 6 month, 9 month and at end of 1 year
|
|
Number of patients with change in MELD score in both groups.
Time Frame: 3 month, 6 month, 9 month and at end of 1 year
|
MELD minimum value=6 and maximum value=40
|
3 month, 6 month, 9 month and at end of 1 year
|
Incidence of Hepatocellular carcinoma at 6 months between two groups.
Time Frame: 6 months
|
6 months
|
|
Incidence of Hepatocellular carcinoma at 12 months between two groups.
Time Frame: 12 months
|
12 months
|
|
Incidence of Portal vein thrombosis at 6 months between two groups.
Time Frame: 6 months
|
6 months
|
|
Incidence of Portal vein thrombosis at 12 months between two groups.
Time Frame: 12 months
|
12 months
|
|
Number of patients with adverse events in both the groups.
Time Frame: 6 months and 12 months
|
6 months and 12 months
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Liver Diseases
- Fibrosis
- Liver Cirrhosis
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Enzyme Inhibitors
- Platelet Aggregation Inhibitors
- Protective Agents
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Antioxidants
- Phosphodiesterase Inhibitors
- Free Radical Scavengers
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Radiation-Protective Agents
- Carvedilol
- Pentoxifylline
Other Study ID Numbers
- ILBS-Cirrhosis-62
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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