Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline

Patrick Northup, MD

Status: Terminated

Conditions: Hepatorenal Syndrome

Treatments: Drug: Pentoxyfylline; Drug: Placebo; Drug: AMO Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02123576

17365

Details and patient eligibility

About

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.

Full 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

Enrollment: 12 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

12 participants in 2 patient groups, including a placebo group

Treatment

Experimental group

Description:

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:

Drug: AMO Therapy

Drug: Pentoxyfylline

Placebo

Placebo Comparator group

Description:

This is a standard placebo pill.

Treatment:

Drug: Placebo

Drug: AMO Therapy