Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension

Phase 4

Terminated

• Conditions: Pulmonary Hypertension
• Interventions: Drug: Iloprost and nitric oxide administration

• Registration Number: NCT03044314
• Lead Sponsor: Duke University

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.

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 Timeline

• Study First Submitted: 2016-10-06
• Study First Submitted QC: 2017-02-02
• Study First Posted: 2017-02-07
• Study Start: 2017-07-21
• Primary Completion: 2019-06-20
• Study Completion: 2020-05-19
• Disposition First Submitted: 2022-01-21
• Results First Submitted: 2022-10-31
• Status Verified: 2024-03
• Results First Submitted QC: 2024-03-06
• Last Update Submitted: 2024-03-06
• Results First Posted: 2024-04-02
• Disposition First Posted: 2024-04-02
• Last Update Posted: 2024-04-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 27

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%

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Iloprost and nitric oxide administration	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Association of Change in Pressures After Vasodilator Challenge With Clinical Outcomes	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.
Number of Participants Who Respond After Vasodilator Challenge	Baseline and during vasodilator inhalation, 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.
Number of Participants With Clinical Response to Vasodilator Challenge by Echo	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.
Percent Change in Systolic Pulmonary Arterial Pressure After Vasodilator Challenge	Baseline and during vasodilator inhalation, approximately 30 minutes

Trial Locations

Locations (1)

Duke University Health System; 🇺🇸 Durham, North Carolina, United States