Inhaled Nitric Oxide (INO) In Hypoxic Respiratory Failure

Sponsor

Mallinckrodt (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT00922532

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

This Phase 3, Double-blind, Randomized, Placebo controlled, multicenter study is to confirm the efficacy of inhaled nitric oxide for the management of hypoxic respiratory failure associated with pulmonary hypertension in preterm infants.

Study subjects will be administered either inhaled nitric oxide or placebo to determine if there is a change in oxygenation.

Condition or Disease	Intervention/Treatment	Phase
Hypoxic Respiratory Failure With Pulmonary Hypertension	Drug: Inhaled Nitric Oxide Drug: Placebo	Phase 3

Detailed Description

This trial will be a multi-center, double blind, placebo-controlled, randomized clinical trial. All mothers identified with prolonged rupture of membranes and/or oligohydramnios, and all inborn infants < 30 weeks gestational age (GA) at birth will be screened for enrollment. Infants who meet all inclusion and exclusion criteria within the first 48 hours after birth will be randomized to either inhaled NO starting at 20 ppm, or matched placebo, delivered by means of a blinded INOvent® delivery device. Randomization will be stratified by center and treatment will be assigned using an interactive voice or web-based response system (IVRS). All infants will receive up to 14 days of therapy, following a dose reduction schedule. The primary outcome measure will be change in oxygenation at 1 hour after start of therapy. In order to determine the effects of iNO therapy on survival and need for mechanical ventilation, cross-over will not be allowed.

This clinical trial will attempt to demonstrate if pre-term infants may benefit from treatment with nitric oxide for inhalation. A multi-center study is necessary to recruit an appropriate number of subjects, and to reflect the variability of standard practice across the different participating centers. All treatment assignments are blinded in order to minimize the risk of bias in treatment and data collection. In addition, a concurrent placebo group has been chosen as the most appropriate control group since there may be temporal, institutional and national variations in average outcomes. Methemoglobin levels will be measured locally and will collected in a blinded manner.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Inhaled Nitric Oxide For The Treatment Of Hypoxic Respiratory Failure With Pulmonary Hypertension In Preterm Infants

Study Start Date :

Nov 1, 2009

Anticipated Primary Completion Date :

Oct 1, 2011

Anticipated Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inhaled Nitric Oxide Inhaled Nitric Oxide	Drug: Inhaled Nitric Oxide Inhaled Nitric Oxide will be administered continuously starting at 20ppm through an INOvent delivery system for up to 14 days. Other Names: INOmax
Placebo Comparator: Nitrogen Nitrogen Placebo	Drug: Placebo Nitrogen gas will be administered in the same manor as the experimental drug

Arm

Intervention/Treatment

Experimental: Inhaled Nitric Oxide

Inhaled Nitric Oxide

Drug: Inhaled Nitric Oxide

Inhaled Nitric Oxide will be administered continuously starting at 20ppm through an INOvent delivery system for up to 14 days.

Other Names:

INOmax

Placebo Comparator: Nitrogen

Nitrogen Placebo

Drug: Placebo

Nitrogen gas will be administered in the same manor as the experimental drug

Outcome Measures

Primary Outcome Measures

Arterial Blood Gases [Day 1 through Day 6]

Secondary Outcome Measures

Methemoglobin levels [Treatment Duration]
Vital Signs [Study Duration]
Adverse Events [Study Duration]
cGMP Levels [Day 1 through 14]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 48 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Preterm infants who:

Are in-born at < 30 weeks gestational age
Weigh 500-1250 grams
Have hypoxic respiratory failure requiring mechanical ventilation with FiO2 > 0.8 to maintain SaO2 ≥ 85% in the first 48 hours after birth after use of exogenous surfactant
Have minimal parenchymal lung disease by chest X ray

Exclusion Criteria:

Preterm infants who:

Have ten minute Apgar score < 5
Have life-threatening anomalies (cardiac, thoracic, chromosomal) or congenital diaphragmatic hernia with lung hypoplasia, or any child who will not receive complete intensive care
Have bilateral Grade IV Intraventricular Hemorrhage (IVH)
Are dependent on right to left shunting to maintain the systemic circulation
Have received prior iNO therapy
Have had treatment with investigational medications