Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension (OVATION)

• ClinicalTrials.gov Identifier: NCT03044314
• Recruitment Status: Recruiting
• First Posted: February 7, 2017
• Last Update Posted: February 20, 2020
• Sponsor: Duke University
• Collaborator: Actelion
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Hypertension	Drug: Illoprost and nitric oxide administration	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: OUTPATENT VASODILATOR ASSESSMENT USING ILOPROST IN PULMONARY HYPERTENSION (The OVATION Study)
• Actual Study Start Date: July 21, 2017
• Estimated Primary Completion Date: December 1, 2020
• Estimated Study Completion Date: December 1, 2020

Arms and Interventions

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: Illoprost 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 Name: Ventavis

Outcome Measures

Primary Outcome Measures :

1. Change in invasively measured pulmonary artery pressures after challenge with NO and iloprost [ Time Frame: Baseline and approximately 30 minutes ]
   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.

Secondary Outcome Measures :

1. Change in echocardiographic and invasively measured parameters after vasodilator challenge [ Time Frame: Baseline and approximately 30 minutes ]
   Compare the percent change in echocardiographic parameters measured after vasodilator challenge with percent change of invasively measured vasodilator response.
2. Change in PA pressure and mean pressure determined invasively after vasodilator challenge [ Time Frame: Baseline and approximately 30 minutes ]
   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.
3. Clinical response to vasodilator challenge by echo [ Time Frame: Baseline, approximately 30 minutes, 3 months, and 12 months ]
   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.
4. Association of change in pressures after vasodilator challenge with clinical outcomes [ Time Frame: 3 months and 12 months ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Richard A Krasuski, MD; 919-684-2407; richard.krasuskI@duke.edu

Locations

United States, North Carolina

Duke University Health System; Recruiting

Durham, North Carolina, United States, 27710

Contact: Richard A Krasuski, MD 919-684-2407 richard.krasuski@duke.edu

Contact: Stephanie Newbold, MS 919-613-4728 stephanie.newbold@duke.edu

Sub-Investigator: Jordan Awerbach, MD

Sponsors and Collaborators

Duke University

Actelion

Investigators

• Principal Investigator: Richard A Krasuski, MD; Duke Health

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03044314
• Other Study ID Numbers: Pro00075840
• First Posted: February 7, 2017
• Last Update Posted: February 20, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Duke University:

pulmonary hypertension; vasodilator challenge; echocardiography; outcomes; iloprost; inhaled nitric oxide

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Nitric Oxide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters; Protective Agents