Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline

Not Applicable

Terminated

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

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Treatment	AMO Therapy	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	Pentoxyfylline	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
Placebo	Placebo	This is a standard placebo pill.
Placebo	AMO Therapy	This is a standard placebo pill.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Success	14 days	We define this as a decrease in serum creatinine level to \<1.5 mg/dL without dialysis or death

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment Failure	up to day 14	Defined as creatinine level above baseline value after day 7, dialysis or death
Number of Participants With Combined Outcome of Treatment Success and Partial Response	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
Overall Survival	up to 1 year	This will be the combination of transplant free survival and those patients who received liver transplant
Transplant Free Survival	day 30 and 180
Change in Serum Creatinine From Baseline	baseline and 14 days