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Revatio Portal-Pulmonary Arterial Hypertension Trial (RePo1)

Primary Purpose

Portopulmonary Hypertension

Status

Terminated

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Sildenafil

Placebo

About this trial

This is an interventional treatment trial for Portopulmonary Hypertension

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Lawson Health Research Institute (London Health Sciences Centre Research Inc.)
University Health Network
Institut universitaire de cardiologie et de pneumologie de Québec

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Revatio

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change from baseline in PVR after 16 weeks of treatment

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

Hospitalizations

Death

Complications of liver disease

MELD score

Renal dysfunction

Desaturation

Change in 6MWD from baseline

Change in baseline WHO functional class

Change in Brain Natruretic Peptide (BNP) from baseline

Change from baseline in CAMPHOR and SF-36 measures of quality of life

Full Information

NCT ID

NCT01517854

First Posted

December 14, 2011

Last Updated

September 25, 2019

Sponsor

University Health Network, Toronto

1. Study Identification

Unique Protocol Identification Number

NCT01517854

Brief Title

Revatio Portal-Pulmonary Arterial Hypertension Trial

Acronym

RePo1

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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Terminated

Why Stopped

Poor recruitment.

Study Start Date

November 14, 2012 (Actual)

Primary Completion Date

October 30, 2017 (Actual)

Study Completion Date

May 14, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Portopulmonary Hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Revatio

Arm Type

Active Comparator

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Sildenafil

Intervention Description

20 mg Revatio (sildenafil citrate) three times a day

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from baseline in PVR after 16 weeks of treatment

Time Frame

16 weeks

Secondary Outcome Measure Information:

Title

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

Title

Hospitalizations

Time Frame

16 weeks

Title

Death

Time Frame

16 weeks

Title

Complications of liver disease

Time Frame

16 weeks

Title

MELD score

Time Frame

16 weeks

Title

Renal dysfunction

Time Frame

16 weeks

Title

Desaturation

Time Frame

16 weeks

Title

Change in 6MWD from baseline

Time Frame

16 weeks

Title

Change in baseline WHO functional class

Time Frame

16 weeks

Title

Change in Brain Natruretic Peptide (BNP) from baseline

Time Frame

16 weeks

Title

Change from baseline in CAMPHOR and SF-36 measures of quality of life

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John T Granton

Organizational Affiliation

University Health Network, Toronto

Official's Role

Study Chair

Facility Information:

Facility Name

Lawson Health Research Institute (London Health Sciences Centre Research Inc.)

City

London

State/Province

Ontario

ZIP/Postal Code

N6C 2R5

Country

Canada

Facility Name

University Health Network

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2N2

Country

Canada

Facility Name

Institut universitaire de cardiologie et de pneumologie de Québec

City

Québec

ZIP/Postal Code

G1V 4G5

Country

Canada

12. IPD Sharing Statement

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Revatio Portal-Pulmonary Arterial Hypertension Trial

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