Iloprost Power 15 in Pulmonary Arterial Hypertension (PROWESS 15)

A Multicenter, Double-blind, Randomized, Placebo-controlled, Crossover Study to Assess the Effects of a Single Dose of Iloprost Power 15 on Exercise Capacity in Patients With Symptomatic Pulmonary Arterial Hypertension

Patients with symptomatic idiopathic pulmonary arterial hypertension (IPAH), or familial pulmonary arterial hypertension (FPAH) or pulmonary hypertension associated with Human immunodeficiency virus (HIV) or drugs/toxins in New York Heart Association (NYHA) functional class II to IV at baseline, naive to PAH treatment or currently being treated with a stable dose of either bosentan, ambrisentan or sildenafil will be enrolled in the PROWESS 15 study. This randomized, double blind, placebo-controlled, crossover, and single-dose study will determine whether a single inhaled dose of iloprost using the power 15 disc improves exercise capacity compared to placebo in patients with pulmonary arterial hypertension (PAH).

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: iloprost (5 µg); Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LKH Universitätsklinikum Graz
• Germany
  • Dresden, Germany, D-01307
    • Universitätsklinikum Carl-Gustav-Carus
• United States
  • California
    • La Jolla, California, United States, 92037
      • UCSD Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Torrance, California, United States, 90502
      • Liu Center for Pulmonary Hypertension - LA Biomedical Research Institute at Harbor-UCLA
  • Delaware
    • Newark, Delaware, United States, 19713
      • Lung Health & Sleep Enhancement Center, LLC
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Pulmonary & Critical Care of Atlanta
    • Decatur, Georgia, United States, 30033
      • Atlanta Institute for Medical Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • Iowa City, Iowa, United States, 52245
      • Mercy Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Associates
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University Of Nebraska Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7020
      • University of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Clinical Trial Center
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Health System
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Lexington, South Carolina, United States, 29072
      • Lexington Pulmonary & Critical Care
  • Texas
    • Dallas, Texas, United States, 75390-8550
      • UT Southwestern Medical Center Heart Lung and Vascular Center
    • Houston, Texas, United States, 77030
      • University of Texas Medical School
  • Utah
    • American Fork, Utah, United States, 84003
      • Central Utah Clinic, P.C.
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, VA
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Hospitals T/A Sentara Cardiovascular Research Institute
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Respiratory Consultants
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Hospital & Clinics
    • Milwaukee, Wisconsin, United States, 53215
      • Comprehensive Cardiovascular Care LLP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent prior to initiation of any study mandated procedure,
• Patients with symptomatic idiopathic, or familial pulmonary arterial hypertension or pulmonary hypertension associated with human immunodeficiency virus (HIV) or drugs/toxins in NYHA functional class II to IV.
• Women of childbearing potential must have a negative urine pregnancy test and must use an adequate method of contraception during the study and for 28 days after discontinuation of the study drug.

Exclusion Criteria:

• Pulmonary arterial hypertension related to any condition other than those specified in the inclusion criteria,
• Pulmonary arterial hypertension associated with significant venous or capillary involvement (Pulmonary capillary wedge pressure (PCWP) > 15 mmHg),
• Known pulmonary veno-occlusive disease, or pulmonary capillary hemangiomatosis,
• Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 65% of predicted value after bronchodilator administration,
• Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value,
• Pregnant or breast-feeding women,
• Systemic hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg on repeated measurement),
• Systolic blood pressure < 95 mmHg,
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C,
• Chronic renal insufficiency defined by serum creatinine > 2.5 mg/dL (221 μmol/L) or ongoing dialysis,
• Clinically relevant bleeding disorder or active bleeding,
• For those patients on monotherapy, any contraindication to bosentan, ambrisentan, or sildenafil, according to product label,
• Known hypersensitivity to iloprost or any of its excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active / placebo; Single dose of iloprost (5 µg) on study day 2 followed by single dose of placebo on study day 3	Drug: iloprost (5 µg); Single dose of iloprost 5 µg using I-neb(R) Adaptive Aerosol Delivery (AAD(R)) System power setting 15 disc; Other Names: Ventavis(R); Drug: placebo; Single dose of matching placebo using I-neb(R) Adaptive Aerosol Delivery (AAD(R)) System power setting 15 disc
Placebo Comparator: Placebo / active; Single dose of placebo on study day 2 followed by single dose of iloprost (5 µg) on study day 3	Drug: iloprost (5 µg); Single dose of iloprost 5 µg using I-neb(R) Adaptive Aerosol Delivery (AAD(R)) System power setting 15 disc; Other Names: Ventavis(R); Drug: placebo; Single dose of matching placebo using I-neb(R) Adaptive Aerosol Delivery (AAD(R)) System power setting 15 disc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute-walk Distance (6MWD)	The 6-minute walk test was performed 20-40 minutes after treatment. This was a non-encouraged test (the person conducting the test did not encourage the patient to walk farther or faster) that measured the distance covered over a 6-minute walk. It was conducted by a trained member of the site staff who was listed on the site's delegation of authority sheet. For patients who had never performed a 6-minute walk test previously, a training test was requested before the qualifying tests for randomization.	Study day 2 or study day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Borg Dyspnea Score	The Borg scale is a category-ratio scale, commonly used to evaluate the effects of exercise on dyspnea. The original and modified scales have ratio properties ranging from 0 = nothing at all to 10 = very, very severe, with descriptors from 0 to 10. Descriptors have been modified by others so that 10 has been labeled "extremely severe," or "the worst possible dyspnea imaginable." Reliability and validity have been reported in a general population and in patients with PAH as well as other respiratory conditions.	Study day 2 or study day 3

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Laila Rouault, MD, Actelion

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: July 1, 2008
• First Submitted That Met QC Criteria: July 2, 2008
• First Posted (Estimate): July 3, 2008

Study Record Updates

• Last Update Posted (Estimate): September 28, 2015
• Last Update Submitted That Met QC Criteria: September 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: iloprost; pulmonary arterial hypertension; Ventavis; inhaled treatment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: AC-063A301