Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension

Pulmonary Hypertension Clinical Trial

— OVATION  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03044314
• Other study ID #: Pro00075840
• Status: Terminated
• Phase: Phase 4
• Start date: July 21, 2017
• Est. completion date: May 19, 2020

Study information

• Verified date: March 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: May 19, 2020
• Est. primary completion date: June 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University Health System	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Actelion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Invasively Measured Pulmonary Artery Pressures After Challenge With iNO (Inhaled Nitrous Oxide) and Iloprost		Baseline and approximately 30 minutes
Secondary	Percent Change in Systolic Pulmonary Arterial Pressure After Vasodilator Challenge		Baseline and during vasodilator inhalation, approximately 30 minutes
Secondary	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
Secondary	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
Secondary	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