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slow enrollment
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| Name | Class |
|---|---|
| Actelion | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Iloprost and nitric oxide administration | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Iloprost and nitric oxide administration | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Invasively Measured Pulmonary Artery Pressures After Challenge With iNO (Inhaled Nitrous Oxide) and Iloprost | Baseline and approximately 30 minutes |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard A Krasuski, MD | Duke Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Health System | Durham | North Carolina | 27710 | United States |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who completed the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Invasively Measured Pulmonary Artery Pressures After Challenge With iNO (Inhaled Nitrous Oxide) and Iloprost | Participants who completed the study. Each participant was analyzed after challenge with iNO and after challenge with iloprost. | Posted | Mean | Standard Deviation | percent change | Baseline and approximately 30 minutes |
|
Up to 12 months
Inhalation of iNO for 5 minutes with immediate off-effect when stopped. Inhalation of iloprost for 30 minutes and 20-30 minute half-life (negligible effect at 2 hours). Patients observed for hypotension, dizziness, cough, bleeding, etc. All patients observed in the cath lab and holding area after inhalation for >2 hours post-administration. Questioned about symptoms prior to discharge. Mid-term clinical outcome data will be collected at 3 months and at 12 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard Krasuski | Duke University Medical Center | 919-681-6195 | richard.krasuski@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 11, 2016 | Oct 31, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D016285 | Iloprost |
| ID | Term |
|---|---|
| D011465 | Prostaglandins, Synthetic |
| D011453 | Prostaglandins |
| D015777 | Eicosanoids |
| D005231 | Fatty Acids, Unsaturated |
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|
|
| 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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | 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. |
|
|
|
| Secondary | Percent Change in Systolic Pulmonary Arterial Pressure After Vasodilator Challenge | Participants who completed the study. Two patients refused to undergo echocardiography and repeat inhalation of iloprost. | Posted | Mean | Standard Deviation | percentage of change | 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. | Participants who completed the study. Each participant was analyzed after challenge with iNO and after challenge with iloprost. | Posted | Count of Participants | Participants | Baseline and during vasodilator inhalation, approximately 30 minutes |
|
|
|
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| 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. | Participants who completed the study. Two patients refused to undergo echocardiography and repeat inhalation of iloprost. | Posted | Count of Participants | Participants | 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. | 0 participants had a change of echocardiographically estimated pressures, as indicated in outcome #4 | Posted | 3 months and 12 months |
|
|
| 0 |
| 27 |
| 0 |
| 27 |
| 0 |
| 27 |
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| D002318 |
| Cardiovascular Diseases |
| D005227 |
| Fatty Acids |
| D008055 | Lipids |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |
| Title | Measurements |
|---|
|
| 12 months |
|