Clinical trial NCT02123576: Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline
Official title: Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline: A Placebo Controlled, Blinded Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatorenal Syndrome
Keywords: Hepatorenal syndrome
Renal failure
Pentoxyfylline
Liver transplantation
Cirrhosis
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2014-04-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Each hospitalized subject will undergo pre-dosing screening with review of his or her history and physical exam from the day of enrollment and safety assessment to ensure no contraindication to use of PTX. Type I HRS will be defined according to the criteria put forth by the American Association for the Study of Liver Disease as (1) cirrhosis with ascites; (2) serum creatinine greater than 1.5 mg/dL; (3) no improvement of serum creatinine (decrease to a level of 1.5 mg/dL or less) after at least two days with diuretic withdrawal and volume expansion with albumin; (4) absence of shock; (5) no current or recent treatment with nephrotoxic drugs; and (6) absence of parenchymal kidney disease as indicated by proteinuria \>500 mg/day, microhematuria (\>50 red blood cells per high power field), and/or abnormal renal ultrasonography. Baseline testing will be obtained from hospitalization records, including but not limited to chemistry panel, liver function testing, urinalysis, urine electrolytes, coagulation studies, blood cultures, chest x-ray, diagnostic paracentesis, abdominal ultrasound with Doppler.

Subjects will take either placebo three times a day or 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. Treatment will be continued for 14 days unless a study endpoint has been reached at which time either PTX or placebo will be stopped

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment Success
timeFrame: 14 days
Secondary outcomes:
measure: Change in Serum Creatinine From Baseline
timeFrame: baseline and 14 days
measure: Incidence of Treatment Failure
timeFrame: up to day 14
measure: Number of Participants With Combined Outcome of Treatment Success and Partial Response
timeFrame: 14 days
measure: Transplant Free Survival
timeFrame: day 30 and 180
measure: Overall Survival
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Virginia
name: Patrick G Northup, MD MHS
role: STUDY_DIRECTOR
affiliation: University of Virginia
name: Jonathan G Stine, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morgan TR, McClain CJ. Pentoxifylline and alcoholic hepatitis. Gastroenterology. 2000 Dec;119(6):1787-91. doi: 10.1053/gast.2000.20826. No abstract available.
citation: 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.
citation: 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.
citation: 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.
citation: 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.