Ignite Creation Date:
2025-12-24 @ 9:42 PM
Ignite Modification Date:
2025-12-28 @ 11:47 PM
Study NCT ID:
NCT06041932
Status:
UNKNOWN
Last Update Posted:
2023-10-03
First Post:
2023-08-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pentoxifylline Plus Carvedilol vs Carvedilol Monotherapy in Preventing New Decompensation in Stable Cirrhotic Patients With Prior Decompensation
Sponsor:
Institute of Liver and Biliary Sciences, India
Organization:
Study Overview
Official Title:
Pentoxifylline Plus Carvedilol vs Carvedilol Monotherapy in Preventing New Decompensation in Stable Cirrhotic Patients With Prior Decompensation, an Open Label Randomised Control Trial
Status:
UNKNOWN
Status Verified Date:
2023-08
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cirrhotics with decompensation have increased risk of morbidity and mortality. There is increased portal pressure leading to decompensation. Carvedilol is a standard therapy given to cirrhotic patient with clinically significant portal hypertension to reduce portal pressure. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces portal hypertension, decreases lipopolysaccharide-induced liver injury, improves nonalcoholic steatohepatitis, prevents development of HRS in ascites and SAH, prevents hepatopulmonary syndrome. Investigator want to study whether addition of pentoxifylline to carvediolol vs carvedilol monotherapy reduces the risk of mortality and further decompensation in cirrhotics with prior decompensation.
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 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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: