Clinical Trial: Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline: A Placebo Controlled, Blinded Pilot Study

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 Summary:

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


Sponsor: Patrick Northup, MD

Current Primary Outcome: Incidence of treatment success [ Time Frame: 14 days ]

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in serum creatinine from baseline [ Time Frame: 14 days ]
  • Incidence of treatment failure [ Time Frame: Day14 ]
    Defined as creatinine level above baseline value after day 7, dialysis or death
  • Combined increase of treatment success and "partial response [ Time Frame: 14 days ]
    We define as serum creatinine level decreased by >50% from baseline but not to <1.5 mg/dL, without dialysis or HRS recurrence
  • Transplant free survival [ Time Frame: day 30 and 180 ]
  • Composite survival index [ Time Frame: day 30 and 180 ]
    .This will be the combination of transplant free survival and those patients who received liver transplant


Original Secondary Outcome: Same as current

Information By: University of Virginia

Dates:
Date Received: April 18, 2014
Date Started: April 2014
Date Completion: December 31, 2017
Last Updated: May 1, 2017
Last Verified: May 2017