Efficacy of Pentoxifylline and Rifaximin Combination in Pentoxifylline Refractory Clinical and Subclinical Hepatopulmonary Syndrome

Study Overview
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Brief Summary
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The study will be a prospective open labelled double blinded randomized controlled study. The study will be conducted on patients admitted to Department of Hepatology from 2012 to 2014 at Institute of Liver and Biliary Sciences, New Delhi Patients diagnosed as having clinical or subclinical hepatopulmonary syndrome will be started on oral pentoxifylline therapy 400 mg thrice daily for 12 weeks. Patients not responding to this therapy will be given divided into 2 arms with one arm receiving additional Tab Rifaximin 400 mg thrice daily or placebo for 12 weeks.

Conditions
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Hepatopulmonary Syndrome

Intervention / Treatment
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* Drug: pentoxifylline and rifaximin
* Drug: Pentoxifylline and placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of portal hypertension (esophagogastric varices or portal hypertensive gastropathy identified on esophagogastroduodenoscopy, and/or varices seen on computerized tomography scan or ultrasound, and/or splenomegaly with no other explanation, and/or ascites with no other explanation) Intrapulmonary vascular dilatations (IPVDs) diagnosed on contrast echocardiogram (CE) AaDO2 > 15 mm Hg on standing room air arterial blood gas (ABG) Ability and willingness to give informed consent Exclusion Criteria: Age < 18 or > 64 Intrinsic significant cardiopulmonary disease Inability to perform pulmonary function tests Moderate to severe Pulmonary hypertension Advanced hepatic encephalopathy Inadequate echocardiographic window to allow for accurate transthoracic contrast echocardiography Antibiotic use within the last one month Listed for liver transplant in next 4 weeks Current use of exogenous nitrates Active bacterial infections Known malignancy Known intolerance to Pentoxifylline or rifaximin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rifaximin and pentoxifylline<br>Tab Rifaximin 400 mg thrice daily + Pentoxifylline 400 mg thrice daily for 12 weeks | Drug: Pentoxifylline and placebo<br>* Tab Pentoxifylline 400 mg thrice daily + Placebo thrice daily for 12 weeks<br>|
| Active Comparator: pentoxifylline and placebo<br>Tab Pentoxifylline 400 mg thrice daily + Placebo thrice daily for 12 weeks | Drug: pentoxifylline and rifaximin<br>* Tab Rifaximin 400 mg thrice daily + Pentoxifylline 400 mg thrice daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response after 3 months of treatment |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of serious adverse effects leading to withdrawal of the drug |  | 3 months |