Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline

NCT02123576 | Terminated Results

• 1 other identifier: 17365
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Pentoxyfylline therapy in addition to the standard of care of albumin, midodrine and octreotide therapy is superior to the standard of care alone in the treatment of Type I hepatorenal syndrome in the first 14 days of hospitalization.

Conditions

Hepatorenal Syndrome

Keywords

Hepatorenal syndrome; Renal failure; Pentoxyfylline; Liver transplantation; Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Success

  We define this as a decrease in serum creatinine level to \<1.5 mg/dL without dialysis or death

  14 days

Secondary Outcomes (5)

• Change in Serum Creatinine From Baseline

  baseline and 14 days

• Incidence of Treatment Failure

  up to day 14

• Number of Participants With Combined Outcome of Treatment Success and Partial Response

  14 days

• Transplant Free Survival

  day 30 and 180

• Overall Survival

  up to 1 year

Study Arms (2)

Treatment

EXPERIMENTAL

Pentoxyfylline 400mg three times a day or 400mg twice a day for eGFR 10-50 and 400mg once a day for eGFR \<10 for 90 days in addition to standard AMO therapy

Drug: Pentoxyfylline; Drug: AMO Therapy

Placebo

PLACEBO COMPARATOR

This is a standard placebo pill.

Drug: Placebo; Drug: AMO Therapy

Interventions

Pentoxyfylline DRUG

Treatment

Placebo DRUG

Placebo

AMO Therapy DRUG

Albumin, midodrine and octreotide therapy (standard of care for HRS)

Placebo; Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized patients with acute or chronic liver disease
• Type I HRS
• Aged greater than or equal to 18
• Non-pregnant

You may not qualify if:

• Allergy or hypersensitivity to PTX or intolerance to methylxanthines (e.g. caffeine, theophylline)
• Concurrent use of nephrotoxic drugs
• Age less than 18
• Pregnancy
• Uncontrolled bacterial infection
• Renal parenchymal disease (e.g. acute tubular necrosis, glomerular disease, interstitial nephritis and urinary obstruction)
• Shock
• TNF alpha antagonist use
• Subject is institutionalized or a prisoner
• Recent cerebral or retinal hemorrhage (contraindication to PTX)
• Severe or poorly controlled cardiovascular disease as determined by the principal investigator to hinder the ability to adhere to study protocols

Sponsors & Collaborators

• Patrick Northup, MD: lead

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (5)

• Morgan TR, McClain CJ. Pentoxifylline and alcoholic hepatitis. Gastroenterology. 2000 Dec;119(6):1787-91. doi: 10.1053/gast.2000.20826. No abstract available.

  PMID: 11113103 BACKGROUND

• Angeli P. beta-blockers and refractory ascites in cirrhosis: the message of a team of true scientists. J Hepatol. 2011 Oct;55(4):743-4. doi: 10.1016/j.jhep.2011.02.026. Epub 2011 Mar 10. No abstract available.

  PMID: 21396970 BACKGROUND

• Lott JP. Renal failure in cirrhosis. N Engl J Med. 2010 Jan 7;362(1):79; author reply 80-1. doi: 10.1056/NEJMc0910190. No abstract available.

  PMID: 20054052 BACKGROUND

• Spring FA, Dalchau R, Daniels GL, Mallinson G, Judson PA, Parsons SF, Fabre JW, Anstee DJ. The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene. Immunology. 1988 May;64(1):37-43.

  PMID: 2454887 BACKGROUND

• Fallon E, Ehrenwald E, Nazarian GK, Smith CI. TIPS with a polytetrafluoroethylene-lined stent graft and associated haemolytic anaemia. Gut. 2008 Aug;57(8):1180-1. No abstract available.

  PMID: 18628385 BACKGROUND

MeSH Terms

Conditions

Hepatorenal Syndrome; Renal Insufficiency; Fibrosis

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Small sample size due to low numbers of recruitment over a two year study period. Inherent limitations to PTX as this medication cannot be administered through gastric feeding tube owing to it's pharmacologic properties.

Results Point of Contact

• Title: Dr. Jonathan G. Stine
• Organization: The Pennsylvania State University Division of Gastroenterology and Hepatology Milton S. Herhsey Medical Center

jstine@pennstatehealth.psu.edu

717-531-0003

Study Officials

• Patrick G Northup, MD MHS

  University of Virginia

  STUDY DIRECTOR

• Jonathan G Stine, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 18, 2014
• First Posted: April 25, 2014
• Study Start: April 1, 2014
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: May 29, 2019
• Results First Posted: May 29, 2019

Record last verified: 2019-05

Locations

US (1)