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Revatio Portal-Pulmonary Arterial Hypertension Trial (RePo1)

This study is not yet open for participant recruitment.
Verified May 2012 by University Health Network, Toronto
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01517854
First received: December 14, 2011
Last updated: May 22, 2012
Last verified: May 2012
History of Changes
  Purpose

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 Intervention Phase
Portopulmonary Hypertension
 Drug: Sildenafil
Drug: Placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Change from baseline in PVR after 16 weeks of treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Hospitalizations [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Death [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Complications of liver disease [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • MELD score [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Renal dysfunction [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Desaturation [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Change in 6MWD from baseline [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change in baseline WHO functional class [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change in Brain Natruretic Peptide (BNP) from baseline [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in CAMPHOR and SF-36 measures of quality of life [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic testing at selected sites [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Visit 1: 0, 1, 2, 4 hours after dose. Visits 3-5 and/or Termination Visit: only AM pre-dose sample.


Estimated Enrollment: 44
Study Start Date: July 2012
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01517854

Locations
Canada, Ontario
University Health Network Not yet recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: John T Granton            
Principal Investigator: John T Granton            
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Study Chair: John T Granton University Health Network, Toronto
  More Information

No publications provided

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01517854     History of Changes
Other Study ID Numbers: RePo1
Study First Received: December 14, 2011
Last Updated: May 22, 2012
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Sildenafil
Vasodilator Agents
 Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013