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Revatio Portal-Pulmonary Arterial Hypertension Trial (RePo1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01517854
Recruitment Status : Terminated (Poor recruitment.)
First Posted : January 25, 2012
Last Update Posted : September 27, 2019
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Portopulmonary Hypertension Drug: Sildenafil Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 14, 2012
Actual Primary Completion Date : October 30, 2017
Actual Study Completion Date : May 14, 2019

Arm Intervention/treatment
Active Comparator: Revatio Drug: Sildenafil
20 mg Revatio (sildenafil citrate) three times a day

Placebo Comparator: Placebo Drug: Placebo
Placebo identical to Revatio (sildenafil citrate) three times a day

Primary Outcome Measures :
  1. Change from baseline in PVR after 16 weeks of treatment [ Time Frame: 16 weeks ]

Secondary Outcome Measures :
  1. 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 ]
  2. Hospitalizations [ Time Frame: 16 weeks ]
  3. Death [ Time Frame: 16 weeks ]
  4. Complications of liver disease [ Time Frame: 16 weeks ]
  5. MELD score [ Time Frame: 16 weeks ]
  6. Renal dysfunction [ Time Frame: 16 weeks ]
  7. Desaturation [ Time Frame: 16 weeks ]
  8. Change in 6MWD from baseline [ Time Frame: 16 weeks ]
  9. Change in baseline WHO functional class [ Time Frame: 16 weeks ]
  10. Change in Brain Natruretic Peptide (BNP) from baseline [ Time Frame: 16 weeks ]
  11. Change from baseline in CAMPHOR and SF-36 measures of quality of life [ Time Frame: 16 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01517854

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Canada, Ontario
Lawson Health Research Institute (London Health Sciences Centre Research Inc.)
London, Ontario, Canada, N6C 2R5
University Health Network
Toronto, Ontario, Canada, M5G 2N2
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Canada, G1V 4G5
Sponsors and Collaborators
University Health Network, Toronto
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Study Chair: John T Granton University Health Network, Toronto
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Responsible Party: University Health Network, Toronto Identifier: NCT01517854    
Other Study ID Numbers: RePo1
First Posted: January 25, 2012    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents