Inhaled Aerosolized Prostacyclin for Pulmonary Hypertension Requiring Inhaled Nitric Oxide

Study Overview
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Brief Summary
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Acute secondary pulmonary hypertension (PH) often leads to dysfunction of the right ventricle (RV) and can be a significant cause of patient morbidity and mortality. Selective pulmonary vasodilation with inhaled nitric oxide (INO) has become the treatment of choice for this condition. The evidence supporting INO safety and efficacy under these circumstances is sparse, however, and is largely extrapolated from the use of INO in neonatal pulmonary hypertension. Moreover, the high cost and potential toxicity of INO makes the therapy far from ideal. Emerging evidence suggests that inhaled aerosolized prostacyclins such as iloprost may be a favorable alternative therapy.

Detailed Description
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Phase 1- In the original study, 3 doses of Iloprost were given. This was revised after 5 subjects were enrolled in order to study the effects of continuous delivery over a longer period of time. Phase 2 - All remaining subjects received Iloprost as a continuous treatment. The study was designed for an enrollment of 200 subjects and was ended early.

Official Title
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Inhaled Aerosolized Prostacyclin for Pulmonary Hypertension Requiring Inhaled Nitric Oxide

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Inhaled Iloprost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical evidence of pulmonary hypertension (PH) requiring INO therapy as prescribed by the attending physician. Indwelling arterial catheter. Signed informed consent Exclusion Criteria: Clinically unstable circulatory condition requiring epinephrine > 0.1 mcg/kg/min or levophed, or already meeting treatment failure criteria (see section 5.3 below) Known hypersensitivity to prostacyclin compounds Patients receiving sildenafil or bosentan Refusal by the attending physician
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2: Inhaled Iloprost continuous<br>Each subject will have a stable dose of INO therapy as established by the attending physicians for at least one hour. Initial baseline data collection will then be made. A 20 mcg dose of Iloprost will be given initially. During this treatment there will be a nitric oxide titration to 0. Iloprost will be aerosolized continuously at a dose of 5-30mcg/hour for as long as the attending physician deems it necessary to deliver vasodilator therapy. | Drug: Inhaled Iloprost<br>* A 20 mcg dose of Iloprost will be given initially.<br>* Other names: Ventavis;|
| Experimental: Phase 1: Inhaled Iloprost 3 doses<br>Each subject will have a stable dose of INO therapy as established by the attending physicians for at least one hour. Initial baseline data collection will then be made. A 20 mcg dose of Iloprost will be given initially. During this treatment there will be a nitric oxide titration to 0. Iloprost will be aerosolized three different times on hour apart. Thirty minutes after the last iloprost dose, INO will be added back at the previous (baseline) dose. | Drug: Inhaled Iloprost<br>* A 20 mcg dose of Iloprost will be given initially.<br>* Other names: Ventavis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Oxygen Saturation (SpO2) From Baseline | Readings were taken from the medical record and the data may not have been present at the exact time frames. | 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours | 
| Percent Change in Oxygen Saturation (SpO2) From Baseline |  | dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour) | 
| Change in Mean Heart Rate From Baseline |  | 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours | 
| Change in Mean Heart Rate From Baseline |  | dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour) | 
| Number of Treatment Failures | Treatment failure is defined as Central venous pressure (CVP) ≥ 20 mm Hg and any one of the following: Cardiac Index (CI) >/= 1.8 L/min/m2 Administration of >/=0.1 ug/kg/min Epinephrine or Norepinephrine MAP </= 50 mmHg (or as appropriate for age in pediatrics). SvO2</= 55% (or < 45% for patients with R to L intracardiac shunting and, thus, cyanosis at baseline.} | as long as subject was on drug up to approximately 24 hours | 
| Change in Mean Pulmonary Artery Pressure (mPAP) From Baseline |  | 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours | 
| Change in Mean Pulmonary Artery Pressure (mPAP) From Baseline |  | dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiac Output (CO) From Baseline |  | 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours | 
| Change in Cardiac Output (CO) From Baseline |  | dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour) | 
| Change in Mean Venous Oxygen Saturation (SvO2) From Baseline | SvO2 represents an average of all the venous oxygen saturations of the various organs and tissues. | 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours | 
| Change in Mean Venous Oxygen Saturation (SvO2) From Baseline |  | dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary hypertension