Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension

Study Overview
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Brief Summary
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This study will compare the clinical efficacy of inhaled iloprost as an invasive, selective vasodilator in the cardiac catheterization laboratory in patients with pulmonary hypertension to the gold standard of inhaled nitric oxide. It will also examine whether echocardiographic estimates of response to inhaled iloprost can predict responsiveness to invasive vasodilator testing in patients with pulmonary hypertension.

Detailed Description
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Iloprost was the first inhaled prostacyclin analogue to be FDA-approved for the treatment of pulmonary arterial hypertension. Iloprost aerosol has been shown to significantly improve pulmonary hemodynamics in patients with idiopathic pulmonary hypertension (PH), with an effect greater than nitric oxide and sildenafil. It has also been shown to be more effective than nitric oxide at reducing pulmonary arterial pressure (PAP) than prostacyclin infusion when used in the cardiac catheterization laboratory. Because of its administration through inhalational means, iloprost has the advantage of selective action on the pulmonary vasculature with avoidance of the systemic side effects that plague many of the other treatments for PH. The investigators intend to compare the efficacy of inhaled iloprost in reducing pulmonary artery pressure to the gold standard of nitric oxide in patients with pulmonary hypertension. Without an established noninvasive algorithm to identify beneficial hemodynamic response to vasodilators, patients with pulmonary hypertension (PH) are routinely subjected to expensive and invasive testing. Echocardiography is routinely used to facilitate a diagnosis of PH and a few echocardiographically-derived estimates have even been shown to correlate with vasodilator responsiveness and survival. Dynamic, real time changes in echocardiographic parameters have not been previously evaluated as a predictor of vasodilator responsiveness or of clinical outcome. The investigators will examine whether echocardiographic changes in response to inhaled iloprost can predict invasively derived vasodilator responsiveness and help assess prognosis in patients with pulmonary hypertension, possibly even obviating the need for invasive testing.

Official Title
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Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension (The OVATION Study)

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Illoprost and nitric oxide administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients no younger than 18 years of age Recently diagnosed pulmonary hypertension (defined by RV systolic pressure of ≥ 40 mmHg as measured by echocardiography), going for invasive hemodynamic assessment for pulmonary hypertension Normal left ventricular function defined as a left ventricular ejection fraction (LVEF) greater than or equal to 50% Exclusion Criteria: Heart failure (LVEF < 50%, diastolic dysfunction > stage 1, history or symptoms of left heart failure) - Group II pulmonary hypertension 2+ or higher MR or AI Inadequate echocardiographic windows Pregnancy Systolic blood pressure ≤ 90 mmHg

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iloprost and nitric oxide administration<br>Each patient will receive 40 ppm inhaled nitric oxide and 2.5-5 mcg inhaled iloprost in the catheterization laboratory with assessment of hemodynamic response. Patients will also receive 2.5-5 mcg iloprost during echocardiographic assessment. | Drug: Illoprost and nitric oxide administration<br>* Iloprost will be administered by the I-neb ultrasonic nebulizer (Respironics, Cedar Grove, New Jersey) with a disposable attachment that allows for administration to a supine patient at a concentration of 10 µg/ml with a 10 minute dose of 2.5 µg and then repeated to a cumulative dose of 5.0 µg if tolerated.<br>* Other names: Ventavis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in invasively measured pulmonary artery pressures after challenge with NO and iloprost | Compare the percent change in the invasively measured PAP after challenge with NO compared to the percent change in invasively measured PAP after challenge with iloprost. | Baseline and approximately 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in echocardiographic and invasively measured parameters after vasodilator challenge | Compare the percent change in echocardiographic parameters measured after vasodilator challenge with percent change of invasively measured vasodilator response. | Baseline and approximately 30 minutes | 
| Change in PA pressure and mean pressure determined invasively after vasodilator challenge | Dichotomize the vasodilator response into responders and nonresponders, based on a 10 mmHg drop in PA pressure and a mean pressure <40mmHg determined invasively. Receiver operating characteristic (ROC) curves will evaluate the echocardiographic parameters for prediction of vasodilator response. | Baseline and approximately 30 minutes | 
| Clinical response to vasodilator challenge by echo | Measure the clinical response to vasodilator challenge during echocardiography, by tracking the changes of echo parameters (such as RVSP) before and after iloprost challenge, as well as through the 3 and 12 month follow-up visits. | Baseline, approximately 30 minutes, 3 months, and 12 months | 
| Association of change in pressures after vasodilator challenge with clinical outcomes | Observe the association of the percent change of echocardiographically estimated pressures after iloprost challenge with mid-term clinical outcomes (all cause mortality and all cause mortality +/- hospitalization). These data will be collected at 3 months and at 12 months. Data from all hospitalizations will be collected though we will make special note of those related to pulmonary hypertension. | 3 months and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary hypertension, vasodilator challenge, echocardiography, outcomes, iloprost, inhaled nitric oxide