Iloprost Power 15 in Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: iloprost (5 µg)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ventavis, iloprost, inhaled treatment, pulmonary arterial hypertension