Inhaled Nitric Oxide by Oxygen Hood in Neonates

This study has been completed.
Sponsor:
Information provided by:
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00732537
First received: August 8, 2008
Last updated: NA
Last verified: August 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Respiratory Failure
Infant
Persistent Fetal Circulation
Drug: inhaled Nitric Oxide
Drug: Oxygen (>90% by hood) - standard therapy
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhaled Nitric Oxide in Neonates With Elevated A-aDO2 Gradients Not Requiring Mechanical Ventilation

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • PaO2 one hour after the first hour of study gas [ Time Frame: one hour after the first hour of study gas ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Alveolar-arterial oxygen gradient (A-a DO2) [ Time Frame: one hour of exposure to treatment gas ] [ Designated as safety issue: No ]
  • oxygen saturation by pulse oximetry (SpO2) [ Time Frame: continuously through the study ] [ Designated as safety issue: Yes ]
  • need for mechanical ventilation [ Time Frame: Continuously through the study ] [ Designated as safety issue: Yes ]
  • duration of oxygen therapy [ Time Frame: continuously through the study ] [ Designated as safety issue: No ]
  • Methemoglobin level in post-ductal arterial blood (MetHb) [ Time Frame: Hourly until completion of study in infant ] [ Designated as safety issue: Yes ]
  • Platelet count [ Time Frame: As needed if bleeding ] [ Designated as safety issue: Yes ]
  • Systemic blood pressure [ Time Frame: hourly ] [ Designated as safety issue: Yes ]
  • Environmental NO and NO2 exposure [ Time Frame: Hourly ] [ Designated as safety issue: Yes ]

Enrollment: 8
Study Start Date: March 1999
Study Completion Date: June 2005
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
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.
Other Names:
  • iNO
  • Nitric Oxide
Placebo Comparator: 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).
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.
Other Names:
  • Oxygen
  • Head box

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.

  Eligibility

Ages Eligible for Study:   up to 1 Week
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732537

Locations
United States, Alabama
Regional Neonatal ICU, University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Namasivayam Ambalavanan, MD University of Alabama at Birmingham
Principal Investigator: Waldemar A Carlo, MD University of Alabama at Birmingham
  More Information

Publications:
Responsible Party: Namasivayam Ambalavanan MD and Waldemar A. Carlo MD, Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00732537     History of Changes
Other Study ID Numbers: F990225003
Study First Received: August 8, 2008
Last Updated: August 8, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Hypoxia
Respiratory failure
Infant, term
Nitric oxide

Additional relevant MeSH terms:
Nitric Oxide
Persistent Fetal Circulation Syndrome
Respiratory Insufficiency
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases
Respiration Disorders
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
Vasodilator Agents
Cardiovascular Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on August 01, 2014