Inhaled Nitric Oxide by Oxygen Hood in Neonates

Respiratory Failure Clinical Trial

Official title:

Inhaled Nitric Oxide in Neonates With Elevated A-aDO2 Gradients Not Requiring Mechanical Ventilation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00732537
• Other study ID #: F990225003
• Status: Completed
• Phase: Phase 4
• First received: August 8, 2008
• Last updated: August 8, 2008
• Start date: March 1999
• Est. completion date: June 2005

Study information

• Verified date: August 2008
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 2005
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 1 Week

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infant
• Persistent Fetal Circulation
• Persistent Fetal Circulation Syndrome
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Regional Neonatal ICU, University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PaO2 one hour after the first hour of study gas		one hour after the first hour of study gas	No
Secondary	Alveolar-arterial oxygen gradient (A-a DO2)		one hour of exposure to treatment gas	No
Secondary	oxygen saturation by pulse oximetry (SpO2)		continuously through the study	Yes
Secondary	need for mechanical ventilation		Continuously through the study	Yes
Secondary	duration of oxygen therapy		continuously through the study	No
Secondary	Methemoglobin level in post-ductal arterial blood (MetHb)		Hourly until completion of study in infant	Yes
Secondary	Platelet count		As needed if bleeding	Yes
Secondary	Systemic blood pressure		hourly	Yes
Secondary	Environmental NO and NO2 exposure		Hourly	Yes