Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension (OVATION)

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

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Iloprost and nitric oxide administration

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iloprost and nitric oxide administration; 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: Iloprost and nitric oxide administration; 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.; Other Names: Ventavis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Invasively Measured Pulmonary Artery Pressures After Challenge With iNO (Inhaled Nitrous Oxide) and Iloprost	Baseline and approximately 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Systolic Pulmonary Arterial Pressure After Vasodilator Challenge		Baseline and during vasodilator inhalation, approximately 30 minutes
Number of Participants Who Respond 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 during vasodilator inhalation, approximately 30 minutes
Number of Participants With 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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Actelion
• Investigators: Principal Investigator: Richard A Krasuski, MD, Duke Health

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2017
• Primary Completion (Actual): June 20, 2019
• Study Completion (Actual): May 19, 2020

Study Registration Dates

• First Submitted: October 6, 2016
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimated): February 7, 2017

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: echocardiography; outcomes; pulmonary hypertension; iloprost; inhaled nitric oxide; vasodilator challenge
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Platelet Aggregation Inhibitors; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide; Iloprost
• Other Study ID Numbers: Pro00075840

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No