Revatio Portal-Pulmonary Arterial Hypertension Trial (RePo1)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01517854
First received: December 14, 2011
Last updated: April 11, 2014
Last verified: April 2014

December 14, 2011
April 11, 2014
October 2012
November 2016   (final data collection date for primary outcome measure)
Change from baseline in PVR after 16 weeks of treatment [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01517854 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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.
Not Provided
Not Provided
 
Revatio Portal-Pulmonary Arterial Hypertension Trial
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Portopulmonary Hypertension
  • Drug: Sildenafil
    20 mg Revatio (sildenafil citrate) three times a day
  • Drug: Placebo
    Placebo identical to Revatio (sildenafil citrate) three times a day
  • Active Comparator: Revatio
    Intervention: Drug: Sildenafil
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Enrolling by invitation
44
Not Provided
November 2016   (final data collection date for primary outcome measure)

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.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01517854
RePo1
Yes
University Health Network, Toronto
University Health Network, Toronto
Not Provided
Study Chair: John T Granton University Health Network, Toronto
University Health Network, Toronto
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP