Inhaled Nitric Oxide by Oxygen Hood in Neonates

NCT ID: NCT00732537

Last Updated: 2008-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-03-31
• Study Completion Date: 2005-06-30

Brief Summary

Inhaled nitric oxide (iNO) improves oxygenation in term infants with respiratory failure. However, iNO has been primarily used in infants receiving mechanical ventilation. This study is a pilot study to determine if iNO given into an oxygen hood is effective in improving oxygenation in term and near-term infants who have poor oxygenation but who are not yet mechanically ventilated.

Detailed Description

Inhaled nitric oxide (iNO) is currently used in the management of ventilated neonates with hypoxemic respiratory failure. We have shown that iNO administered by oxygen hood reduces pulmonary vascular resistance in hypoxia- and group B streptococcus-induced pulmonary hypertension in an animal model (J Perinatol 2002; 22:50-6). Our objective was to determine the feasibility of iNO administration by oxygen hood in neonates with respiratory failure. Methods: A masked randomized controlled trial was performed on eight infants with respiratory failure. Inclusion criteria were: gestation>34 weeks, age<7 days, with post-ductal arterial line, and A-aDO2 400-600 on two consecutive blood gases. Infants were randomized to study gas (iNO at 20 ppm or equivalent flow of O2) for 1 hr which was then weaned over the next 4 hours. The iNO was introduced into an oxygen hood using an INOvent (INO Therapeutics, Inc). The primary outcome was the PaO2 one hour after randomization. Environmental leakage of NO and NO2 were measured. Results: Four infants were randomized to iNO and four to O2 (controls). Two of the four infants given iNO had an increase in PaO2 of >100 mm Hg, while oxygenation was unchanged in the controls. Methemoglobinemia and other adverse effects were not noted in any infant. Environmental levels of NO and NO2 were minimal (<1ppm) to undetectable at >0.3m from the hood. Conclusions: Administration of iNO by oxygen hood is feasible. Larger randomized controlled trials are required to measure the efficacy and determine an appropriate target population for this technique.

Conditions

Respiratory Failure; Infant; Persistent Fetal Circulation

Keywords

Hypoxia; Respiratory failure; Infant, term; Nitric oxide

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Inhaled Nitric Oxide

iNO started at 20 ppm for 1 hour. The gas was then weaned hourly over the next 4 hours (20 ppm to 10 to 5 to 2.5 to 1 to off).

Group Type: EXPERIMENTAL

inhaled Nitric Oxide

Intervention Type: DRUG

iNO started at 20 ppm for 1 hour, then weaned hourly over the next 4 hours (20 ppm to 10 to 5 to 2.5 to 1 to off). If \>5% drop in oxygen saturation was observed during weaning, study gas was increased to the previous concentration and weaning done 2 hourly. If \> 5% drop in oxygen saturation or \>5% Methemoglobin was observed during initial administration, the study gas would be weaned over 30 minutes and the infant would exit. The iNO was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda). The INOvent ® was connected to the oxyhood by placing the injector module inline on the dry side of the humidifier chamber. Monitoring of O2, NO2, NO was done by placing the end of the sample line inside the oxyhood. A "Masking Shield" covered the Display/Control Panel and Cylinder Gauges, in order to maintain masking of the intervention. Only the respiratory therapist and research coordinator was aware of the allocation assignment.

Placebo

The Oxygen at high concentration (\>90%), which was standard therapy for PPHN, was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda).

Group Type: PLACEBO_COMPARATOR

Oxygen (>90% by hood) - standard therapy

Intervention Type: DRUG

Oxygen (\>90% by hood, standard therapy for PPHN prior to intubation) was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda). The INOvent ® was connected to the oxyhood by placing the injector module inline on the dry side of the humidifier chamber. If the baby was randomized to the control group and did not receive NO, the INOmax® cylinder was opened and used only to pressurize the system, which prevented the "Low NO Pressure" alarm. A "Masking Shield" covered the Display/Control Panel and Cylinder Gauges, in order to maintain masking of the intervention. Only the respiratory therapist and research coordinator was aware of the allocation assignment.

Interventions

inhaled Nitric Oxide

iNO started at 20 ppm for 1 hour, then weaned hourly over the next 4 hours (20 ppm to 10 to 5 to 2.5 to 1 to off). If \>5% drop in oxygen saturation was observed during weaning, study gas was increased to the previous concentration and weaning done 2 hourly. If \> 5% drop in oxygen saturation or \>5% Methemoglobin was observed during initial administration, the study gas would be weaned over 30 minutes and the infant would exit. The iNO was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda). The INOvent ® was connected to the oxyhood by placing the injector module inline on the dry side of the humidifier chamber. Monitoring of O2, NO2, NO was done by placing the end of the sample line inside the oxyhood. A "Masking Shield" covered the Display/Control Panel and Cylinder Gauges, in order to maintain masking of the intervention. Only the respiratory therapist and research coordinator was aware of the allocation assignment.

Intervention Type: DRUG

Oxygen (>90% by hood) - standard therapy

Oxygen (\>90% by hood, standard therapy for PPHN prior to intubation) was introduced into an oxygen hood (Oxydome ™ disposable hood from Maxtex ® Inc.) using an INOvent (Datex-Ohmeda). The INOvent ® was connected to the oxyhood by placing the injector module inline on the dry side of the humidifier chamber. If the baby was randomized to the control group and did not receive NO, the INOmax® cylinder was opened and used only to pressurize the system, which prevented the "Low NO Pressure" alarm. A "Masking Shield" covered the Display/Control Panel and Cylinder Gauges, in order to maintain masking of the intervention. Only the respiratory therapist and research coordinator was aware of the allocation assignment.

Intervention Type: DRUG

Other Intervention Names

iNO; Nitric Oxide; Oxygen; Head box

Eligibility Criteria

Inclusion Criteria

• gestation >34 weeks at birth
• age <7 days
• post-ductal arterial line
• an A-aDO2 of 400 to 600 on two blood gases, at least 30 minutes apart.

Exclusion Criteria

• Infants with major malformations
• Infants with cardiac disease

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 1 Week
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Department of Pediatrics, University of Alabama at Birmingham

Principal Investigators

Namasivayam Ambalavanan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Waldemar A Carlo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

Regional Neonatal ICU, University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

Ambalavanan N, St John E, Carlo WA, Bulger A, Philips JB 3rd. Feasibility of nitric oxide administration by oxygen hood in neonatal pulmonary hypertension. J Perinatol. 2002 Jan;22(1):50-6. doi: 10.1038/sj.jp.7210652.

Reference Type: BACKGROUND

PMID: 11840243 (View on PubMed)

Other Identifiers

F990225003

Identifier Type: -

Identifier Source: org_study_id