Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline

Hepatorenal Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02123576
• Other study ID #: 17365
• Status: Terminated
• Phase: N/A
• Start date: April 2014
• Est. completion date: December 31, 2017

Study information

• Verified date: May 2019
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: December 31, 2017
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatorenal Syndrome
• Syndrome

Intervention

Drug:
• Pentoxyfylline

• Placebo

• AMO Therapy
Albumin, midodrine and octreotide therapy (standard of care for HRS)

Locations

Country	Name	City	State
United States	University of Virginia Health System	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Patrick Northup, MD

Country where clinical trial is conducted

United States, 

References & Publications (5)

Angeli P. ß-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. — View 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. — View 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. — View Citation

Morgan TR, McClain CJ. Pentoxifylline and alcoholic hepatitis. Gastroenterology. 2000 Dec;119(6):1787-91. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Success	We define this as a decrease in serum creatinine level to <1.5 mg/dL without dialysis or death	14 days
Secondary	Change in Serum Creatinine From Baseline		baseline and 14 days
Secondary	Incidence of Treatment Failure	Defined as creatinine level above baseline value after day 7, dialysis or death	up to day 14
Secondary	Number of Participants With Combined Outcome of Treatment Success and Partial Response	We define as serum creatinine level decreased by >50% from baseline but not to <1.5 mg/dL, without dialysis or HRS recurrence	14 days
Secondary	Transplant Free Survival		day 30 and 180
Secondary	Overall Survival	This will be the combination of transplant free survival and those patients who received liver transplant	up to 1 year