Pentoxyphilline Versus Fecal Microbiota Therapy in Severe Alcoholic Hepatitis

Treatment for severe alcoholic hepatitis patients not eligible for steroid therapy is a dilemma. Pentoxyfilline has been shown to have no improvement in outcomes as per current studies and liver transplantation is with great risk of recidivism in this difficult to treat cohort of patients. Dysbiosis forms the central role in severe alcoholic hepatitis patients and modulation of gut microbiota by way of healthy donor fecal transplantation could prove to be a novel way to treating these patients who are ineligible for standard therapy. This study utilizes correction of dysbiosis in severe alcoholic hepatitis and surveys outcomes with the same with respect to survival and liver disease severity scores.

Study Overview

• Status: Completed
• Conditions: Alcoholic Hepatitis
• Intervention / Treatment: Drug: Pentoxiphylline; Drug: Stool microbiota transplantation

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver and Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients with a diagnosis of severe alcoholic hepatitis who are steroid ineligible, are non responders or are intolerant
• Severe alcoholic hepatitis defined as Maddrey's Discriminant Function Score (4.6 x (PT test - control))+ S.Bilirubin in mg/dl of more than 32 OR a patient of alcoholic hepatitis (defined as AST:ALT ratio > 2:1) who presents with any grade of hepatic encephalopathy
• Conventional therapy defined as oral steroid therapy (Wysolone ® 40mg once a day for 7 days)
• Failure of therapy defined as a Lille Model Score (http://www.lillemodel.com) of >0.45 at day 8 of steroid therapy OR emergence of complications of steroid therapy or intolerance to steroid protocol or ineligible for steroid therapy.
• Ineligibility for steroid therapy includes - Renal dysfunction, evidence of active sepsis or foci of sepsis, gastro intestinal bleeding and disseminated intravascular coagulation, steroid intolerance, steroid related uncontrolled hyperglycemia which precludes therapy, uncontrolled diabetes mellitus

• A Psychologist will be arranged for recipients who are on Fecal Transplant protocol for psychological support throughout the period of one week, during which the transplant procedure will be performed

  1. Healthy persons who are willing for faeces donation have to be a close family member
  2. The donor will be required to give a written consent for faeces donation

  3. Once consent is taken, the donor will have to undergo the following screening measures:

     1. Clostridium difficile toxins A and B by EIA
     2. Routine bacterial culture for enteric pathogens in stool
     3. Ova and parasites
     4. Blood serology for viruses - human immunodeficiency virus [HIV, type 1 and 2] HAV IgM, HBsAg, anti HCV Ab

Exclusion Criteria:

• Active gastrointestinal bleeding
• Intracranial bleeding
• Multi-organ failure on mechanical ventilation
• On high inotropic support
• Paralytic ileus
• Pregnancy
• Sepsis
• Failure to provide consent
• Have abnormal bowel motions
• Have abdominal complaints
• Have symptoms indicative of irritable bowel syndrome
• Have extensive travel history or predisposing factors for potentially transmittable diseases
• Have chronic alcohol intake
• Have history of substance abuse
• Are less than 18 years or more than 60 years of age
• Have HIV and Hepatitis Risk factors
• Have enteric infections
• Have inflammatory bowel disease history
• Have chronic constipation or diarrhea
• Have prior abdominal surgery or GI neoplasms
• Have Metabolic Syndrome
• Have Systemic Autoimmunity
• Have atopic diseases
• Have food and respiratory allergies
• Have any chronic pain syndromes
• Have chronic Neurologic disorders
• Have Neurodevelopmental disorders
• Have had antibiotics for any indication taken within the last 2 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pentoxiphylline	Drug: Pentoxiphylline
Active Comparator: Stool Microbiota Transplantation	Drug: Stool microbiota transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival at 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement in SOFA (Sequential Organ Failure Assessment) score at 3 months	3 month
Improvement in CTP (Child Turcotte Pugh Score) score at 3 months	3 month
Improvement in MELD (Model for End Stage Liver Disease) score at 3 months	3 month
Short term mortality in both groups	30 days

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): July 27, 2016
• Study Completion (Actual): July 27, 2016

Study Registration Dates

• First Submitted: May 23, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimate): May 29, 2015

Study Record Updates

• Last Update Posted (Actual): August 15, 2019
• Last Update Submitted That Met QC Criteria: August 14, 2019
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Hepatitis; Hepatitis A; Hepatitis, Alcoholic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: ILBS-AH-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No