Comparison of Inhaled Nitric Oxide and Oxygen in Patient Reactivity During Acute Pulmonary Vasodilator Testing

This study has been completed.
Sponsor:
Information provided by:
INO Therapeutics
ClinicalTrials.gov Identifier:
NCT00626028
First received: February 20, 2008
Last updated: October 18, 2010
Last verified: October 2010
  Purpose

A minimum of 100 patients will be enrolled in the study to demonstrate which diagnostic treatment (oxygen or nitric oxide) is most capable of identifying patients with a reactive pulmonary vascular bed. Each patient will be given all three treatment regimen, nitric oxide, oxygen, and the comparison treatment (nitric oxide plus oxygen), with a wash out period of 10 minutes between each dose. Patients will be randomized at the time of enrollment to determine which comparison treatment they will receive.


Condition Intervention Phase
Idiopathic Pulmonary Arterial Hypertension
Congenital Heart Disease With Pulmonary Hypertension
Cardiomyopathy
Drug: Nitric Oxide for inhalation
Drug: Oxygen
Drug: Nitric Oxide plus Oxygen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Comparison of Supplemental Oxygen and Nitric Oxide for Inhalation in the Evaluation of the Reactivity of the Pulmonary Vasculature During Acute Pulmonary Vasodilator Testing

Resource links provided by NLM:


Further study details as provided by INO Therapeutics:

Primary Outcome Measures:
  • Reversible Pulmonary Hypertension (Vasoreactivity)as Defined by Hemodynamic Measurements [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Hemodynamic measurements (heart rate, systolic arterial blood pressure,diastolic arterial blood pressure, mean arterial pressure, mean central venous pressure, systolic pulmonary arterial pressure, diastolic pulmonary arterial pressure, mean pulmonary wedge pressure and cardiac output) were used to measure reversible pulmonary hypertension (vasoreactivity).


Secondary Outcome Measures:
  • Surgical Procedures at 1 Year [ Time Frame: 1 year after treatment ] [ Designated as safety issue: No ]
    The 1 year follow-up survival assessment consisted of a telephone call to subjects to obtain information on surgeries received pertaining to pulmonary or cardiac disease

  • Adverse Events [ Time Frame: treatment 1 through treatment 3 ] [ Designated as safety issue: Yes ]
  • Serious Adverse Events [ Time Frame: 12 hours after discontinuation of gas or dischange (whichever comes first) ] [ Designated as safety issue: Yes ]
  • Surgical Procedures at 3 Years [ Time Frame: 3 years after treatment ] [ Designated as safety issue: No ]
    The 3 year follow-up survival assessment consisted of a telephone call to subjects to obtain information on surgeries received pertaining to pulmonary or cardiac disease


Enrollment: 136
Study Start Date: September 2004
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Nitric Oxide
Nitric Oxide
Drug: Nitric Oxide for inhalation
Nitric Oxide (NO) for inhalation, given at 80ppm over 10 minutes using an INOvent®
Other Name: INOmax®
Sham Comparator: Oxygen
Oxygen
Drug: Oxygen
100% oxygen (O2) for inhalation, given at 80ppm over 10 minutes using an INOvent®
Other Name: Oxygen
Active Comparator: Nitric Oxide plus Oxygen Drug: Nitric Oxide plus Oxygen
Nitric Oxide (NO) for inhalation plus oxygen, given at 80ppm over 10 minutes using an INOvent® delivery system
Other Name: Inhaled Nitric Oxide, Oxygen

Detailed Description:

This is an open, randomized, prospective, multi-center study designed to demonstrate which diagnostic treatment is most capable of identifying patients with a reactive pulmonary vascular bed. A minimum of 100 patients will be enrolled in the study to compare the number of patients with reversible pulmonary hypertension (vasoreactivity) due to nitric oxide for inhalation and oxygen as compared to 100% oxygen. This primary objective will be obtained by measuring the decrease in mean pulmonary arterial pressure (PAPm) ≥ 20% and no decrease in cardiac index (within 5%) in patients with Idiopathic Pulmonary Arterial Hypertension (IPAH) or Congenital Heart Disease (CHD) who do not have an unrestricted shunt at the level of the ventricle or ductus arteriosis, and by measuring the decrease in PAPm ≥ 20% and no decrease in cardiac index (within 5%) and decrease in pulmonary vascular resistance index (PVRI) ≥ 25% and no decrease in cardiac index (within 5%) in patients with cardiomyopathy or CHD who have unrestricted shunt at the level of the ventricle or ductus arteriosis. Additionally, comparison of the incidence and types of drug related and serious adverse events as well as the number of patients with reversible pulmonary hypertension due to nitric oxide for inhalation alone compared to 100% oxygen and to oxygen with nitric oxide for inhalation will also be assessed.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. must have any one of these three disease categories:

    • Idiopathic Pulmonary Arterial Hypertension

      • PAPm > 25mmHg at rest , pulmonary capillary wedge pressure (PCWP) ≤ 15mmHg, and PVRI> 3 u•m^2 or diagnosed clinically with no previous catheterization
    • CHD with pulmonary hypertension repaired and unrepaired

      • PAPm > 25mmHg at rest and PVRI> 3 u•m^2 or diagnosed clinically with no previous catheterization
    • Cardiomyopathy

      • PAPm > 25mmHg at rest and PVRI> 3 u•m^2 or diagnosed clinically with no previous catheterization
  2. Scheduled to undergo right heart catheterization to assess pulmonary vasoreactivity by acute pulmonary vasodilation testing.
  3. Male or female, ages 4 weeks to 18 years, inclusive
  4. Signed informed consent/assent

Exclusion Criteria:

  1. Focal pulmonary infiltrates on chest radiograph.
  2. Diagnosed with severe obstructive or restrictive pulmonary disease that is significantly contributing to the patient's pulmonary hypertension.
  3. Received treatment with nitric oxide for inhalation within 30 dyas prior to study initiation, are on other investigational medications, nitroglycerin, sodium nitroprusside, sildenafil, other PDE-5 inhibitors, or prostacyclin
  4. Pregnant (urine human chorionic gonadotropin (HCG +) positive)
  5. Baseline PCWP > 20 mmHg
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00626028

Locations
United States, California
Lucile Salter Packard Children's Hospital at Stanford
Stanford, California, United States, 94304
United States, Colorado
The Children's Hospital
Denver, Colorado, United States, 80218
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Missouri
St. Louis Children's Hospital
St. Louis, Missouri, United States, 63110
United States, New York
New York Presbyterian Hospital
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
Columbus Children's Hospital
Columbus, Ohio, United States, 43205
United States, South Carolina
The Medical University of South Carolina
Charleston, South Carolina, United States, 29425
France
CHU Timone - Département de cardiologie
Marseille, France
Hôpital d'Enfants
Nandoevre Les Nancy, France
Hôpital NECKER - Enfants Malades
Paris, France
Netherlands
Beatrix Children's Hospital / University Hospital Groningen
Groningen, Netherlands
Spain
Hospital Sant Joan de Déu de Barcelona
Barcelona, Spain
Unidad de Cardiologia Infantil - Hospital Vall d'Hebrón
Barcelona, Spain
Instituto Pediátrico del Corazón - Hospital Materno Infatil Doce de Octubre
Madrid, Spain
Hospital Gregorio Maranon
Madrid, Spain
United Kingdom
Royal Brompton Hospital
London, United Kingdom
Southampton University Hospitals Trust - Wessex Cardiothoracic Centre
Southampton, United Kingdom
Sponsors and Collaborators
INO Therapeutics
Investigators
Study Director: James Baldassarre, MD INO Therapeutics
  More Information

No publications provided by INO Therapeutics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: James Baldassarre, MD, INO Therapeutics
ClinicalTrials.gov Identifier: NCT00626028     History of Changes
Other Study ID Numbers: INOT 22
Study First Received: February 20, 2008
Results First Received: September 21, 2009
Last Updated: October 18, 2010
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española del Medicamento y Productos Sanitarios
The Netherlands: Rijksinstituut voor Volksgezondheid en Milieu

Keywords provided by INO Therapeutics:
Pulmonary Vasculature
Nitric Oxide
INOmax®
Acute Lung Injury
Pulmonary Vasodilator Testing
Idiopathic Pulmonary Arterial Hypertension
Congenital Heart Disease
reversible pulmonary hypertension
vasoreactivity

Additional relevant MeSH terms:
Hypertension, Pulmonary
Heart Diseases
Hypertension
Heart Defects, Congenital
Cardiomyopathies
Lung Diseases
Respiratory Tract Diseases
Cardiovascular Diseases
Vascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities
Nitric Oxide
Vasodilator Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on April 22, 2014