Hepatopulmonary SyndromePhase 1NCT00593658
Pilot Study of Pentoxifylline for Hepatopulmonary Syndrome
A Phase 1 study testing pentoxifylline in people with Hepatopulmonary Syndrome, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Hepatopulmonary Syndrome
- What is being tested?
- pentoxifylline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2004to Oct 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient undergoing liver transplantation evaluation for cirrhosis
- HPS (positive contrast echocardiography, hypoxemia, no other cause)
- PaO2 < 65mmHg
- ability and willingness to give informed consent
Who cannot join
- Patients under the age of 19
- active bacterial infections
- known malignancy
- intrinsic cardiopulmonary disease
- known intolerance to pentoxifylline
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: Open Label Single Arm Pilot Study of Pentoxifylline in Advanced Hepatopulmonary Syndrome
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.
- Conditions
- Hepatopulmonary Syndrome
- Being tested
- pentoxifylline
- Keywords
- hypoxemia, liver transplantation evaluation, cirrhosis
- Medical subject headings
- Hepatopulmonary Syndrome, Hypoxia, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pentoxifyllineDrug
pentoxifylline extended release 800mg PO TID for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| single | Experimental | Not described Receives: Drug: pentoxifylline |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient
Measured: 8 weeks
Secondary outcomes (1)
adverse events and safety of pentoxifylline therapy
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2008 (estimated)
- Study startJun 2004
- Primary completionOct 2006
- Study completionOct 2006
Why it stopped: Poor tolerability of drug and side effects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatopulmonary SyndromeStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Investigators
- Michael B Fallon, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00593658
- Sponsor's protocol ID
- F030604005
- Other IDs
- R03DK065958
- Status last verified
- Jan 2008
- First submitted
- 3 Jan 2008
- Last updated
- 9 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 18668653
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Single Arm Pilot Study of Pentoxifylline in Advanced Hepatopulmonary Syndrome
- ClinicalTrials.gov ID
- NCT00593658
- Acronym / sponsor ID
- F030604005
- Conditions
- Hepatopulmonary Syndrome
- Keywords
- hypoxemia, liver transplantation evaluation, cirrhosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor tolerability of drug and side effects
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Jun 2004
- Primary completion
- Oct 2006 (actual)
- Study completion
- Oct 2006 (actual)
- First posted
- 15 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single | Experimental | Drug: pentoxifylline |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patient undergoing liver transplantation evaluation for cirrhosis
- HPS (positive contrast echocardiography, hypoxemia, no other cause)
- PaO2 < 65mmHg
- ability and willingness to give informed consent
Key exclusion criteria (5 listed)
- Patients under the age of 19
- active bacterial infections
- known malignancy
- intrinsic cardiopulmonary disease
- known intolerance to pentoxifylline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pentoxifyllinepentoxifylline extended release 800mg PO TID for 8 weeks | Drug | single |
Primary outcome
change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient
Time frame: 8 weeks
1 secondary outcome
adverse events and safety of pentoxifylline therapy
Time frame: 8 weeks
Results and safety
The study was stopped early (reason given: Poor tolerability of drug and side effects). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2015.
- Derived from this study: PubMed 18668653Tanikella 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.
Related trials for Hepatopulmonary Syndrome
Enrolling by invitationObservational study
International Registry of Congenital Portosystemic Shunt (IRCPSS)
Congenital Portosystemic Shunt, CPSS (Congenital Portosystemic Shunt)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael B Fallon, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing pentoxifylline in people with Hepatopulmonary Syndrome, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Poor tolerability of drug and side effects). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in arterial oxygenation (PaO2) and/or alveolar arterial oxygen gradient (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00593658, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2015.