Trial Outcomes & Findings for Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension (NCT NCT03044314)

NCT ID: NCT03044314

Last Updated: 2024-04-02

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 27 participants
• Primary outcome timeframe: Baseline and approximately 30 minutes
• Results posted on: 2024-04-02

Participant Flow

Patients were identified from pulmonary hypertension clinic as well as those referred to the catheterization lab for their initial diagnostic right heart catheterization for evaluation of pulmonary hypertension.

Participant milestones

Measure	Nitric Oxide and Iloprost 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. 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.
Overall Study STARTED	27
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Nitric Oxide and Iloprost 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. 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.
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	1
Overall Study Connector tubing not available	1

Baseline Characteristics

Outpatient Vasodilator Assessment Using Iloprost in Pulmonary Hypertension

Baseline characteristics by cohort

Measure	Nitric Oxide and Iloprost Administration n=23 Participants 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. 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.
Age, Continuous	54.9 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and approximately 30 minutes

Population: Participants who completed the study. Each participant was analyzed after challenge with iNO and after challenge with iloprost.

Outcome measures

Measure	Inhaled Nitric Oxide n=23 Participants 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. 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.	Iloprost n=23 Participants 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. 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.
Change in Invasively Measured Pulmonary Artery Pressures After Challenge With iNO (Inhaled Nitrous Oxide) and Iloprost	10.7 percent change Standard Deviation 7.1	13.3 percent change Standard Deviation 12.5

SECONDARY outcome

Timeframe: Baseline and during vasodilator inhalation, approximately 30 minutes

Population: Participants who completed the study. Two patients refused to undergo echocardiography and repeat inhalation of iloprost.

Outcome measures

Measure	Inhaled Nitric Oxide n=21 Participants 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. 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.	Iloprost 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. 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.
Percent Change in Systolic Pulmonary Arterial Pressure After Vasodilator Challenge	0 percentage of change Standard Deviation 0	—

SECONDARY outcome

Timeframe: Baseline and during vasodilator inhalation, approximately 30 minutes

Population: Participants who completed the study. Each participant was analyzed after challenge with iNO and after challenge with iloprost.

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.

Outcome measures

Measure	Inhaled Nitric Oxide n=23 Participants 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. 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.	Iloprost n=23 Participants 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. 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.
Number of Participants Who Respond After Vasodilator Challenge	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline, approximately 30 minutes, 3 months, and 12 months

Population: Participants who completed the study. Two patients refused to undergo echocardiography and repeat inhalation of iloprost.

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.

Outcome measures

Measure	Inhaled Nitric Oxide n=21 Participants 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. 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.	Iloprost 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. 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.
Number of Participants With Clinical Response to Vasodilator Challenge by Echo 3 months	0 Participants	—
Number of Participants With Clinical Response to Vasodilator Challenge by Echo 12 months	0 Participants	—
Number of Participants With Clinical Response to Vasodilator Challenge by Echo Baseline	0 Participants	—
Number of Participants With Clinical Response to Vasodilator Challenge by Echo 30 minutes	0 Participants	—

SECONDARY outcome

Timeframe: 3 months and 12 months

Population: 0 participants had a change of echocardiographically estimated pressures, as indicated in outcome #4

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.

Outcome measures

Outcome data not reported

Adverse Events

Iloprost and Nitric Oxide Administration

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Richard Krasuski

Duke University Medical Center

Phone: 919-681-6195

Email: richard.krasuski@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place