Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline: A Placebo Controlled, Blinded Pilot Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Sponsor
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Number of Participants With Treatment Success
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
- •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
Arms & Interventions
Treatment
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
Intervention: Pentoxyfylline (Drug)
Treatment
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
Intervention: AMO Therapy (Drug)
Placebo
This is a standard placebo pill.
Intervention: Placebo (Drug)
Placebo
This is a standard placebo pill.
Intervention: AMO Therapy (Drug)
Outcomes
Primary Outcomes
Number of Participants With 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
Secondary Outcomes
- Incidence of Treatment Failure(up to day 14)
- Number of Participants With Combined Outcome of Treatment Success and Partial Response(14 days)
- Overall Survival(up to 1 year)
- Transplant Free Survival(day 30 and 180)
- Change in Serum Creatinine From Baseline(baseline and 14 days)
Investigators
Patrick Northup, MD
Associate Professor
University of Virginia