NCT00593658

Brief Summary

The Hepatopulmonary syndrome (HPS) results from intrapulmonary microvascular dilatation that impairs arterial oxygenation in the setting of cirrhosis or portal hypertension. As many as 10-20% of cirrhotics being evaluated for orthotopic liver transplantation (OLT) have advanced HPS and mortality is greater in those with HPS than in those without HPS. Currently, OLT is the only effective treatment, although post-operative mortality in HPS is increased relative to cirrhotic patients without HPS, with a one-year survival of between 68-80 %. Therefore, an effective medical therapy for advanced HPS could improve both pre-operative and post-operative mortality. Recent work in experimental models of HPS has revealed that both nitric oxide synthase-derived nitric oxide and heme oxygenase-derived carbon monoxide cause intrapulmonary vasodilatation. These alterations appear to be driven in part by TNF-α modulation of pulmonary blood flow and intravascular monocyte accumulation. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with inhibitory effects on TNF-α and has recently been shown to be beneficial in patients with severe alcoholic hepatitis where TNF-α overproduction contributes to liver injury. In experimental HPS, pentoxifylline administration also decreases the severity of oxygenation abnormalities. However, pentoxifylline therapy has been associated with dose limiting side effects in patients with liver disease and the tolerability of pentoxifylline in cirrhotic patients with advanced HPS is unknown. Therefore, this open label single arm clinical trial was designed to evaluate the efficacy and tolerability of 8 weeks of pentoxifylline in cirrhotic patients with advanced HPS being considered for OLT.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2004

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2004

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2006

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2006

Completed
1.3 years until next milestone

First Submitted

Initial submission to the registry

January 3, 2008

Completed
12 days until next milestone

First Posted

Study publicly available on registry

January 15, 2008

Completed
Last Updated

March 9, 2015

Status Verified

January 1, 2008

Enrollment Period

2.3 years

First QC Date

January 3, 2008

Last Update Submit

March 6, 2015

Conditions

Hepatopulmonary Syndrome

Keywords

hypoxemialiver transplantation evaluationcirrhosis

Outcome Measures

Primary Outcomes (1)

  • change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient

    8 weeks

Secondary Outcomes (1)

  • adverse events and safety of pentoxifylline therapy

    8 weeks

Study Arms (1)

single

EXPERIMENTAL
Drug: pentoxifylline

Interventions

pentoxifyllineDRUG

pentoxifylline extended release 800mg PO TID for 8 weeks

single

Eligibility Criteria

Age19 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient undergoing liver transplantation evaluation for cirrhosis
  • HPS (positive contrast echocardiography, hypoxemia, no other cause)
  • PaO2 \< 65mmHg
  • ability and willingness to give informed consent

You may not qualify if:

  • Patients under the age of 19
  • active bacterial infections
  • known malignancy
  • intrinsic cardiopulmonary disease
  • known intolerance to pentoxifylline

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (1)

  • Tanikella R, Philips GM, Faulk DK, Kawut SM, Fallon MB. Pilot study of pentoxifylline in hepatopulmonary syndrome. Liver Transpl. 2008 Aug;14(8):1199-203. doi: 10.1002/lt.21482.

    PMID: 18668653DERIVED

MeSH Terms

Conditions

Hepatopulmonary SyndromeHypoxiaFibrosis

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsPathologic Processes

Intervention Hierarchy (Ancestors)

TheobromineXanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Michael B Fallon, MD

    University of Alabama at Birmingham

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

January 3, 2008

First Posted

January 15, 2008

Study Start

June 1, 2004

Primary Completion

October 1, 2006

Study Completion

October 1, 2006

Last Updated

March 9, 2015

Record last verified: 2008-01

Locations

US(1)