Pentoxifylline (drug) forHepatopulmonary Syndrome (Liver and lung disease)
- Conditions
- Other specified diseases of liver,
- Registration Number
- CTRI/2022/04/041981
- Lead Sponsor
- Institute of Liver and Biliary Sciences
- Brief Summary
Hypothesis
We hypothesize that pentoxifylline in hepatopulmonary syndrome would improve oxygenation by inhibiting TNF alpha and thereby reducing macrophage, endothelium induced NO production compared to placebo
Aim
To study efficacy of pentoxifylline in reducing AaPO2 in hepatopulmonary syndrome when compared to placebo
Methodology:
Study design: Prospective double-blind randomized placebo-controlled trial
DATA and SPECIMEN collection
Patient data, demographics, etiology of liver disease, PFT, abdominal radiological studies will be collected
6-minute walk test will be done at the baseline, 3 months, and 6 months
Sampling for ABG will be performed with the subject seated while breathing room air at baseline and at the end of 3 and 6 months and A-aPO2 values will be calculated using Alveolar gas equation.
TNF alpha levels, vWF, ET-1, VEGFR-3, iNOS, eNOS and IL-1 β levels will be measured at baseline and after 3 and 6 months.
DLCO and exhaled NO will be measured at the baseline and at the end of 3 and 6 months
Blinding
The study drug and placebo will be administered in identical packaging and labelling to ensure that investigators and participants are blinded to study treatment. The study drug and placebo will be labelled with a unique label letter that will be used to allocate treatment to the patient, but the allocation will not be indicated to the investigators or participants. Except for the trial pharmacists and biostatistician, no member of the study team or their extended personnel will have access to the randomization method during the study’s execution. The investigator will get the treatment assignment from trial pharmacists in the case of a medical emergency in which breaking the blind is necessary to give medical care to the participant.
DEFINITION -
Hepatopulmonary syndrome will be defined by
a.Presence of liver disease and / or portal hypertension AND
b.Partial pressure of oxygen <80mm Hg or Alveolar-arterial oxygen gradient [P (A-a)O2 gradient ≥ 15mmHg (0r 20 mmHg for patients >65 years] AND
c.Documented Intrapulmonary Vascular Dilatation by saline contrast echocardiogram
Sample size: Assuming that the improvement in oxygenation in the pentoxifylline group is 50% and that in the control group it would be 1%, with an alpha error of 5% and power of 90% we need to enroll 38 cases in the study.
Further assuming a dropout rate of 5% we need to enroll 40 cases randomized into two groups, 20 each, by block randomization method taking a block size of 4.
STATISTICAL ANALYSIS: Continuous data- Student’s t test
-Nonparametric analysis- Mann Whitney test
-Survival outcome By Kaplan-Meier method curve.
-For all tests, p≤ 0.05 will be considered statistically significant.
-Analysis will be performed using SPSS.
-The analysis will be done with intention to treat and per protocol analysis if applicable.
Stopping rule:
Development of serious adverse effects leading to withdrawal of the drug or death from any cause
Adverse events
It is defined as the new onset event that is considered as a part of intervention which otherwise may be absent in absence of such intervention or therapy. All adverse events will be recorded.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- All
- Target Recruitment
- 40
1.Age 18 – 70 years 2.Evidence of portal hypertension 3.Intrapulmonary vascular dilatation in the form of shunting diagnosed on contrast echocardiogram 4.AaPO2 > 15mmHg on seated room air (ABG) if age <65years and >20mmHg if Age≥ 70 years.
1.Child C cirrhosis with CTP > 10 or with refractory ascites 2.Intrinsic significant cardiopulmonary disease i.PFT showing severe obstructive ventilatory defect (FEV1/FVC < 70) ii.Hepatic hydrothorax, Portopulmonary hypertension iii.Moderate and severe left ventricular systolic dysfunction iv.Inability to perform Pulmonary function test v.Intracardiac shunting 3.Current use of exogenous nitrates 4.Patients already on pentoxifylline 5.Prior intolerance to pentoxifylline 6.Very severe cases of HPS (A-aO2 gradient ≥ 15mm Hg, PO2 <50 mmHg) 7.Active bacterial infections, active hepatic encephalopathy 8.Known malignancy including HCC 9.SBP on secondary prophylaxis 10.CKD with creatinine clearance < 30 11.Enrolled in other trials 12.Has a liver transplant option.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Improvement in AaPO2 gradient by at least 5mmHg or to a value less than 15mm Hg at the end of 6 months from baseline 6 months
- Secondary Outcome Measures
Name Time Method 1.Decrease in grading of intrapulmonary shunting at the end of 3 and 6 months, from baseline as assessed by saline contrast echocardiography 3 and 6 months Change in DLCO fraction of exhaled NO after 3 and 6 months from baseline 3 and 6 months Change in seated and supine saturation and PaO2 at 3 and 6 months from baseline 3 and 6 months Change in VEGFR-3, iNOS, eNOS and IL-1 β at the end of 3 and 6 months from baseline in a subset of patients wherever feasible 3 and 6 months 2.Improvement in Pulmonary function test and 6-minute walk test at the end of 3 and 6 months from baseline 3 and 6 months Change in inflammatory markers - TNF alpha levels, vWF, ET-1, IL-6, S-1-P levels at the end of 3 and 6 months from baseline 3 and 6 months
Trial Locations
- Locations (1)
Institute of Liver and Biliary Sciences
🇮🇳West, DELHI, India
Institute of Liver and Biliary Sciences🇮🇳West, DELHI, IndiaDr Vishnu GirishPrincipal investigator01146300000vishnugirish@gmail.com