Pentoxifylline Therapy in Biliary Atresia

NCT ID: NCT01774487

Last Updated: 2024-01-11

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-02-04

Study Completion Date

2023-02-20

Brief Summary

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The purpose of this study is to determine whether pentoxifylline reduces liver damage in infants with biliary atresia.

Detailed Description

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Biliary atresia (BA) is a devastating liver disease of infancy of unknown etiology, characterized by bile duct obstruction, live fibrosis, and cirrhosis. BA has no known medical treatments. The only proven treatment is a surgical portoenterostomy (the Kasai procedure, or KP) which can achieve bile drainage and improve outcomes in some cases. The KPs success is variable depending on several factors including age of the infant, experience of the surgeon, and extent of liver fibrosis at the time of KP.

In this study, the investigators conduct a phase II trial of a potential new medical therapy for BA: pentoxifylline (PTX). PTX is a methylxanthine derivative closely related to caffeine that has been used safely in infants with other diseases such as sepsis. In adults, PTX has been shown to have a number of properties beneficial to the liver, including preventing liver fibrosis, improving liver regeneration, and reducing cirrhosis-related complications.

The trial's objective is to determine whether PTX has sufficient biological activity against BA to warrant further study. PTX will be administered orally for 90 days as an adjunct to standard therapy (i.e. KP if appropriate). The primary outcome will measure the change in serum conjugated bilirubin levels after 90 days. Secondary outcomes include changes in body weight, serum markers, liver imaging, and time to liver transplant in infants with BA.

Conditions

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Biliary Atresia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pentoxifylline

All newly-diagnosed biliary atresia patients fulfilling the study's inclusion criteria will receive oral pentoxifylline, 20 mg/kg/day divided in three doses for a total of 90 days.

The hospital pharmacy will create a 20 mg/ml oral pentoxifylline solution using 400 mg pentoxifylline tablets and established compounding recipes.

Group Type EXPERIMENTAL

Pentoxifylline

Intervention Type DRUG

20 mg/kg/day divided in 3 doses, given orally for 90 days

Interventions

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Pentoxifylline

20 mg/kg/day divided in 3 doses, given orally for 90 days

Intervention Type DRUG

Other Intervention Names

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Trental

Eligibility Criteria

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Inclusion Criteria

* 0-180 days old
* Diagnosed with biliary atresia through liver biopsy and/or intra-operative cholangiogram
* No previous Kasai portoenterostomy performed at another institution
* Able to take medications orally
* Legal guardian signs consent after understanding risks and investigational nature of study

Exclusion Criteria

* Infants greater than 180 days old
* Infants receiving a Kasai portoenterostomy at another institution
* Infants unable to take medications orally
Maximum Eligible Age

180 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Baylor College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Sanjiv Harpavat

Assistant Professor, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Sanjiv Harpavat, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

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Texas Children's Hospital and Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

References

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Perlmutter DH, Shepherd RW. Extrahepatic biliary atresia: a disease or a phenotype? Hepatology. 2002 Jun;35(6):1297-304. doi: 10.1053/jhep.2002.34170. No abstract available.

Reference Type BACKGROUND
PMID: 12029613 (View on PubMed)

Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 2007 Aug;46(2):566-81. doi: 10.1002/hep.21790.

Reference Type BACKGROUND
PMID: 17661405 (View on PubMed)

Garcia AV, Cowles RA, Kato T, Hardy MA. Morio Kasai: a remarkable impact beyond the Kasai procedure. J Pediatr Surg. 2012 May;47(5):1023-7. doi: 10.1016/j.jpedsurg.2012.01.065.

Reference Type BACKGROUND
PMID: 22595595 (View on PubMed)

Shneider BL, Brown MB, Haber B, Whitington PF, Schwarz K, Squires R, Bezerra J, Shepherd R, Rosenthal P, Hoofnagle JH, Sokol RJ; Biliary Atresia Research Consortium. A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr. 2006 Apr;148(4):467-474. doi: 10.1016/j.jpeds.2005.12.054.

Reference Type BACKGROUND
PMID: 16647406 (View on PubMed)

Weerasooriya VS, White FV, Shepherd RW. Hepatic fibrosis and survival in biliary atresia. J Pediatr. 2004 Jan;144(1):123-5. doi: 10.1016/j.jpeds.2003.09.042.

Reference Type BACKGROUND
PMID: 14722530 (View on PubMed)

Zhang D, Jiang H, Wang Y, Ma J. Pentoxifylline inhibits hepatic stellate cells proliferation via the Raf/ERK pathway. APMIS. 2012 Jul;120(7):572-81. doi: 10.1111/j.1600-0463.2011.02868.x. Epub 2012 Jan 19.

Reference Type BACKGROUND
PMID: 22716212 (View on PubMed)

Andrade Wde C, Tannuri U, da Silva LF, Alves VA. Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals. J Pediatr Surg. 2009 Nov;44(11):2071-7. doi: 10.1016/j.jpedsurg.2009.05.020.

Reference Type BACKGROUND
PMID: 19944210 (View on PubMed)

Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011 Nov;54(5):1610-9. doi: 10.1002/hep.24544. Epub 2011 Aug 24.

Reference Type BACKGROUND
PMID: 21748765 (View on PubMed)

Petrowsky H, Breitenstein S, Slankamenac K, Vetter D, Lehmann K, Heinrich S, DeOliveira ML, Jochum W, Weishaupt D, Frauenfelder T, Graf R, Clavien PA. Effects of pentoxifylline on liver regeneration: a double-blinded, randomized, controlled trial in 101 patients undergoing major liver resection. Ann Surg. 2010 Nov;252(5):813-22. doi: 10.1097/SLA.0b013e3181fcbc5e.

Reference Type BACKGROUND
PMID: 21037437 (View on PubMed)

Lebrec D, Thabut D, Oberti F, Perarnau JM, Condat B, Barraud H, Saliba F, Carbonell N, Renard P, Ramond MJ, Moreau R, Poynard T; Pentocir Group. Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis. Gastroenterology. 2010 May;138(5):1755-62. doi: 10.1053/j.gastro.2010.01.040. Epub 2010 Jan 25.

Reference Type BACKGROUND
PMID: 20102716 (View on PubMed)

Haque KN, Pammi M. Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD004205. doi: 10.1002/14651858.CD004205.pub2.

Reference Type BACKGROUND
PMID: 21975745 (View on PubMed)

Superina R, Magee JC, Brandt ML, Healey PJ, Tiao G, Ryckman F, Karrer FM, Iyer K, Fecteau A, West K, Burns RC, Flake A, Lee H, Lowell JA, Dillon P, Colombani P, Ricketts R, Li Y, Moore J, Wang KS; Childhood Liver Disease Research and Education Network. The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplant-free survival. Ann Surg. 2011 Oct;254(4):577-85. doi: 10.1097/SLA.0b013e3182300950.

Reference Type BACKGROUND
PMID: 21869674 (View on PubMed)

Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

Reference Type BACKGROUND
PMID: 2702835 (View on PubMed)

Best BM, Burns JC, DeVincenzo J, Phelps SJ, Blumer JL, Wilson JT, Capparelli EV, Connor JD; Pediatric Pharmacology Research Unit Network. Pharmacokinetic and tolerability assessment of a pediatric oral formulation of pentoxifylline in kawasaki disease. Curr Ther Res Clin Exp. 2003 Feb;64(2):96-115. doi: 10.1016/S0011-393X(03)00018-3.

Reference Type BACKGROUND
PMID: 24944359 (View on PubMed)

Davenport M, Caponcelli E, Livesey E, Hadzic N, Howard E. Surgical outcome in biliary atresia: etiology affects the influence of age at surgery. Ann Surg. 2008 Apr;247(4):694-8. doi: 10.1097/SLA.0b013e3181638627.

Reference Type BACKGROUND
PMID: 18362634 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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H-31387

Identifier Type: -

Identifier Source: org_study_id

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