Inhaled Aerosolized Prostacyclin for Pulmonary Hypertension Requiring Inhaled Nitric Oxide

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Inhaled Iloprost

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical evidence of pulmonary hypertension (PH) requiring INO therapy as prescribed by the attending physician.
2. Indwelling arterial catheter.
3. Signed informed consent

Exclusion Criteria:

1. Clinically unstable circulatory condition requiring epinephrine > 0.1 mcg/kg/min or levophed, or already meeting treatment failure criteria (see section 5.3 below)
2. Known hypersensitivity to prostacyclin compounds
3. Patients receiving sildenafil or bosentan
4. Refusal by the attending physician

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2: Inhaled Iloprost continuous; 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; A 20 mcg dose of Iloprost will be given initially.; Other Names: Ventavis
Experimental: Phase 1: Inhaled Iloprost 3 doses; 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; A 20 mcg dose of Iloprost will be given initially.; Other Names: Ventavis

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Neil MacIntyre, MD, Duke University

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: June 19, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 23, 2014

Study Record Updates

• Last Update Posted (Estimate): August 26, 2014
• Last Update Submitted That Met QC Criteria: August 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: pulmonary hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: Pro00013737