Portopulmonary HypertensionPhase 2RePo1NCT01517854
Revatio Portal-Pulmonary Arterial Hypertension Trial
A Phase 2 study testing Sildenafil in people with Portopulmonary Hypertension, run by University Health Network, Toronto at 3 sites in Canada.
Trial summary
The investigators propose the first prospective, double blind, randomized controlled trial of treatment for pulmonary arterial hypertension (PAH) related to underlying portal hypertension. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Portopulmonary Hypertension
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 3 sitesCanada
- Study dates
- 14 Nov 2012to 14 May 2019
- Phase
- Phase 2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients with PPHTN.
- A 6MWD test between 150 m and 450 m.
- A pulmonary vascular resistance (PVR) >250 dyn*sec*cm-5, a mean pulmonary artery pressure (PAPmean) ≥25 mmHg due to portal hypertension, and PCWP ≤ 15 mmHg. Right-heart catheterization results for the definite diagnosis of PH must follow the 2 - 6 week pre-treatment phase and not be older than 6 weeks at study start (will be considered as baseline values).
- Portal hypertension defined either clinically or hemodynamically by the presence of cirrhosis (by ultrasound or biopsy) or portal vein thrombosis / obstruction (proven by portal vein Doppler) and any one of the following within one year of entry into the study: 1) Ascites (on ultrasound of the abdomen); 2) Splenomegaly (on ultrasound of the abdomen); 3) Esophageal or Gastric Varices (proven endoscopically); 4) Hepatic-venous pressure gradient (HVPG) > 12 mmHg.
- Treatment naive patients (with respect to PAH specific medication) and patients. Prior use of sildenafil for erectile dysfunction will be permitted.
- 18 to 75 years of age at Visit 1.
- Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period.
- Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures.
Who cannot join
- Participation in another clinical trial during the preceding 3 months.
- Pregnant women or breast feeding women.
- Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator or the sponsor.
- Patients with a history of severe allergies or multiple drug allergies.
- Patients with hypersensitivity to the investigational drug or inactive constituents.
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Lawson Health Research Institute (London Health Sciences Centre Research Inc.)
London, Ontario, N6C 2R5
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, G1V 4G5
University Health Network
Toronto, Ontario, M5G 2N2
About this study
Official title: Revatio Portal-Pulmonary Arterial Hypertension Trial (RePo1 Trial): A Randomized, Double-blinded, Placebo-controlled, Multi-center Study to Evaluate the Effects of Sildenafil Citrate (Revatio) 20 mg TID on Patients With Portal Pulmonary Arterial Hypertension (PPAH)
The investigators propose the first prospective, double blind, randomized controlled trial of treatment for pulmonary arterial hypertension (PAH) related to underlying portal hypertension. Specifically the investigators will evaluate the potential efficacy and safety of sildenafil (Revatio) in a 16 week blinded, multicentre study.
Read the detailed description
PAH is a recognized complication of portal hypertension - termed portal-pulmonary hypertension (PPHTN). In the World Health Organization (WHO) classification PPHTN is categorized as a WHO group 1 condition. This categorization is appropriate as PPHTN shares similar pathological features and clinical presentation and as idiopathic (primary) pulmonary arterial hypertension (PAH). Advances in oral therapies in PAH (idiopathic, connective tissue disease, congenital heart disease) has deferred the need for parenteral therapies, lung transplantation and led to improvements in functional capacity, quality of life and survival. However unlike other forms of PAH, treatment options have not been formally evaluated for PPHTN and there are no approved medical therapies. Patients are unable to pay for medications. Consequently patients continue to endure the natural progression of PAH - a state characterized by progressive right heart failure, disability and death. Furthermore the unacceptable mortality associated with liver transplantation in the presence of hemodynamically significant PAH, leaves them with no therapeutic options. Therefore, new treatment options need to be systematically evaluated.
- Conditions
- Portopulmonary Hypertension
- Being tested
- Sildenafil, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
20 mg Revatio (sildenafil citrate) three times a day
PlaceboDrug
Placebo identical to Revatio (sildenafil citrate) three times a day
| Study group | Role | What they receive |
|---|---|---|
| Revatio | Active comparator | Not described Receives: Drug: Sildenafil |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in PVR after 16 weeks of treatment
Measured: 16 weeks
Secondary outcomes (11)
For patients with a PVR>450 dynes/sec/cm5 at baseline, number of patients who have PVR below 350 dynes/sec/cm5 after 16 weeks of study drug will be determined
Measured: 16 weeks
Hospitalizations
Measured: 16 weeks
Death
Measured: 16 weeks
Complications of liver disease
Measured: 16 weeks
MELD score
Measured: 16 weeks
Renal dysfunction
Measured: 16 weeks
Desaturation
Measured: 16 weeks
Change in 6MWD from baseline
Measured: 16 weeks
Change in baseline WHO functional class
Measured: 16 weeks
Change in Brain Natruretic Peptide (BNP) from baseline
Measured: 16 weeks
Change from baseline in CAMPHOR and SF-36 measures of quality of life
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study start14 Nov 2012
- Primary completion30 Oct 2017
- Study completion14 May 2019
Why it stopped: Poor recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Portopulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John T Granton, Study chair, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01517854
- Sponsor's protocol ID
- RePo1
- Acronym
- RePo1
- Status last verified
- Sep 2019
- First submitted
- 14 Dec 2011
- Last updated
- 27 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Revatio Portal-Pulmonary Arterial Hypertension Trial (RePo1 Trial): A Randomized, Double-blinded, Placebo-controlled, Multi-center Study to Evaluate the Effects of Sildenafil Citrate (Revatio) 20 mg TID on Patients With Portal Pulmonary Arterial Hypertension (PPAH)
- ClinicalTrials.gov ID
- NCT01517854
- Acronym / sponsor ID
- RePo1 / RePo1
- Conditions
- Portopulmonary Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 14 Nov 2012 (actual)
- Primary completion
- 30 Oct 2017 (actual)
- Study completion
- 14 May 2019 (actual)
- First posted
- 25 Jan 2012 (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 investigators propose the first prospective, double blind, randomized controlled trial of treatment for pulmonary arterial hypertension (PAH) related to underlying portal hypertension. Specifically the investigators will evaluate the potential efficacy and safety of sildenafil (Revatio) in a 16 week blinded, multicentre study.
Detailed description
PAH is a recognized complication of portal hypertension - termed portal-pulmonary hypertension (PPHTN). In the World Health Organization (WHO) classification PPHTN is categorized as a WHO group 1 condition. This categorization is appropriate as PPHTN shares similar pathological features and clinical presentation and as idiopathic (primary) pulmonary arterial hypertension (PAH). Advances in oral therapies in PAH (idiopathic, connective tissue disease, congenital heart disease) has deferred the need for parenteral therapies, lung transplantation and led to improvements in functional capacity, quality of life and survival. However unlike other forms of PAH, treatment options have not been formally evaluated for PPHTN and there are no approved medical therapies. Patients are unable to pay for medications. Consequently patients continue to endure the natural progression of PAH - a state characterized by progressive right heart failure, disability and death. Furthermore the unacceptable mortality associated with liver transplantation in the presence of hemodynamically significant PAH, leaves them with no therapeutic options. Therefore, new treatment options need to be systematically evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Revatio | Active comparator | Drug: Sildenafil |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female patients with PPHTN.
- A 6MWD test between 150 m and 450 m.
- A pulmonary vascular resistance (PVR) >250 dyn*sec*cm-5, a mean pulmonary artery pressure (PAPmean) ≥25 mmHg due to portal hypertension, and PCWP ≤ 15 mmHg. Right-heart catheterization results for the definite diagnosis of PH must follow the 2 - 6 week pre-treatment phase and not be older than 6 weeks at study start (will be considered as baseline values).
- Portal hypertension defined either clinically or hemodynamically by the presence of cirrhosis (by ultrasound or biopsy) or portal vein thrombosis / obstruction (proven by portal vein Doppler) and any one of the following within one year of entry into the study: 1) Ascites (on ultrasound of the abdomen); 2) Splenomegaly (on ultrasound of the abdomen); 3) Esophageal or Gastric Varices (proven endoscopically); 4) Hepatic-venous pressure gradient (HVPG) > 12 mmHg.
- Treatment naive patients (with respect to PAH specific medication) and patients. Prior use of sildenafil for erectile dysfunction will be permitted.
Key exclusion criteria (5 listed)
- Participation in another clinical trial during the preceding 3 months.
- Pregnant women or breast feeding women.
- Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator or the sponsor.
- Patients with a history of severe allergies or multiple drug allergies.
- Patients with hypersensitivity to the investigational drug or inactive constituents.
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 |
|---|---|---|
| Sildenafil20 mg Revatio (sildenafil citrate) three times a day | Drug | Revatio |
| PlaceboPlacebo identical to Revatio (sildenafil citrate) three times a day | Drug | Placebo |
Primary outcome
Change from baseline in PVR after 16 weeks of treatment
Time frame: 16 weeks
11 secondary outcomes
For patients with a PVR>450 dynes/sec/cm5 at baseline, number of patients who have PVR below 350 dynes/sec/cm5 after 16 weeks of study drug will be determined
Time frame: 16 weeks
Hospitalizations
Time frame: 16 weeks
Death
Time frame: 16 weeks
Complications of liver disease
Time frame: 16 weeks
MELD score
Time frame: 16 weeks
Renal dysfunction
Time frame: 16 weeks
Desaturation
Time frame: 16 weeks
Change in 6MWD from baseline
Time frame: 16 weeks
Change in baseline WHO functional class
Time frame: 16 weeks
Change in Brain Natruretic Peptide (BNP) from baseline
Time frame: 16 weeks
Change from baseline in CAMPHOR and SF-36 measures of quality of life
Time frame: 16 weeks
Results and safety
The study was stopped early (reason given: Poor recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2019.
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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.
John T Granton study chair
University Health Network, Toronto
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sildenafil in people with Portopulmonary Hypertension, run by University Health Network, Toronto at 3 sites in Canada.
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 8 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 27 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 recruitment.). 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 from baseline in PVR after 16 weeks of treatment (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Sep 2019.