Pentoxifylline Therapy in Biliary Atresia

NCT01774487 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: H-31387
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Biliary Atresia

Keywords

Biliary Atresia; Pentoxifylline; Trental; Serum bilirubin; Conjugated bilirubin; Liver transplantation; Fibrosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Normal Serum Conjugated Bilirubin Levels 12 Weeks After Starting PTX (Pentoxifylline) Therapy

  The investigators will track the serum conjugated bilirubin (CB) levels over the course of therapy in patients receiving 90 days of PTX (this laboratory test is drawn as part of routine care). Normal CB is 0.0-0.3 mg/dL, with a higher number of patients meeting this indicating a better outcome.

  12 weeks after starting therapy

Secondary Outcomes (5)

• Number of Participants Achieving Zero or Positive Weight Z-scores 12 Weeks After Starting PTX Therapy

  12 weeks after starting therapy

• Alanine Amino Transferase (ALT) Levels at 2 Years of Life

  2 years of age

• Spleen Size at 2 Years of Age

  2 years of age

• Time to Liver Transplant

  Baseline and up to two years after therapy finishes

• Platelet Levels at 2 Years of Life

  2 years of age

Study Arms (1)

Pentoxifylline

EXPERIMENTAL

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.

Drug: Pentoxifylline

Interventions

Pentoxifylline DRUG

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

Also known as: Trental

Pentoxifylline

Eligibility Criteria

• Age: Up to 180 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Infants greater than 180 days old
• Infants receiving a Kasai portoenterostomy at another institution
• Infants unable to take medications orally

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Texas Children's Hospital and Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (15)

• 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.

  PMID: 12029613 BACKGROUND

• 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.

  PMID: 17661405 BACKGROUND

• 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.

  PMID: 22595595 BACKGROUND

• 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.

  PMID: 16647406 BACKGROUND

• 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.

  PMID: 14722530 BACKGROUND

• 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.

  PMID: 22716212 BACKGROUND

• 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.

  PMID: 19944210 BACKGROUND

• 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.

  PMID: 21748765 BACKGROUND

• 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.

  PMID: 21037437 BACKGROUND

• 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.

  PMID: 20102716 BACKGROUND

• 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.

  PMID: 21975745 BACKGROUND

• 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.

  PMID: 21869674 BACKGROUND

• 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.

  PMID: 2702835 BACKGROUND

• 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.

  PMID: 24944359 BACKGROUND

• 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.

  PMID: 18362634 BACKGROUND

MeSH Terms

Conditions

Biliary Atresia; Fibrosis

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Because of early termination, this study did not reach the target number of participants needed to achieve target power and statistically reliable results.

Results Point of Contact

• Title: Sanjiv Harpavat
• Organization: Baylor College of Medicine and Texas Children's Hospital

harpavat@bcm.edu

832-824-2099

Study Officials

• Sanjiv Harpavat, MD PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition

Study Record Dates

• First Submitted: January 22, 2013
• First Posted: January 24, 2013
• Study Start: February 4, 2013
• Primary Completion: February 7, 2018
• Study Completion: February 20, 2023
• Last Updated: January 11, 2024
• Results First Posted: October 12, 2023

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)