Inhaled Aerosolized Prostacyclin for Pulmonary Hypertension Requiring Inhaled Nitric Oxide

• ClinicalTrials.gov Identifier: NCT02170519
• Recruitment Status: Terminated
• First Posted: June 23, 2014
• Results First Posted: August 26, 2014
• Last Update Posted: August 26, 2014
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Hypertension	Drug: Inhaled Iloprost	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Inhaled Aerosolized Prostacyclin for Pulmonary Hypertension Requiring Inhaled Nitric Oxide
• Study Start Date: September 2006
• Actual Primary Completion Date: January 2009
• Actual Study Completion Date: January 2009

Arms and Interventions

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 Name: 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 Name: Ventavis

Outcome Measures

Primary Outcome Measures :

1. Percent Change in Oxygen Saturation (SpO2) From Baseline [ Time Frame: 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours ]
   Readings were taken from the medical record and the data may not have been present at the exact time frames.
2. Percent Change in Oxygen Saturation (SpO2) From Baseline [ Time Frame: dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour) ]
3. Change in Mean Heart Rate From Baseline [ Time Frame: 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours ]
4. Change in Mean Heart Rate From Baseline [ Time Frame: dose 1 (1 hour), dose 2 (2 hour), dose 3 (3 hour), combined therapy (4.5 - 5 hour), end INO (6 - 7 hour) ]
5. Number of Treatment Failures [ Time Frame: as long as subject was on drug up to approximately 24 hours ]

   Treatment failure is defined as Central venous pressure (CVP) ≥ 20 mm Hg and any one of the following:

   1. Cardiac Index (CI) >/= 1.8 L/min/m2
   2. Administration of >/=0.1 ug/kg/min Epinephrine or Norepinephrine
   3. MAP </= 50 mmHg (or as appropriate for age in pediatrics).
   4. SvO2</= 55% (or < 45% for patients with R to L intracardiac shunting and, thus, cyanosis at baseline.}
6. Change in Mean Pulmonary Artery Pressure (mPAP) From Baseline [ Time Frame: 30 mins after initial dose, every 2 hours as long as subject was on drug up to approximately 24 hours ]
7. Change in Mean Pulmonary Artery Pressure (mPAP) From Baseline [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: Neil MacIntyre, MD; Duke University

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02170519
• Other Study ID Numbers: Pro00013737
• First Posted: June 23, 2014
• Results First Posted: August 26, 2014
• Last Update Posted: August 26, 2014
• Last Verified: June 2014

Keywords provided by Duke University:

pulmonary hypertension

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Iloprost; Platelet Aggregation Inhibitors; Vasodilator Agents