CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

Study Overview
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Brief Summary
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The objective of the present proposed study is to discover whether, in the nursery setting, administration of low concentration inhaled CO2 (0.8%) for a prolonged period (3 days) can make breathing more regular with less apneic time than that observed with administration of theophylline. The hypothesis to be tested is that inhalation of low concentration CO2 (0.8%) will reduce apnea more effectively and will have fewer adverse side effects than theophylline.

Detailed Description
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To discover whether, in the nursery setting, continuous administration of a low concentration of inhaled CO2 (0.8%) for a prolonged period (3 days) can make breathing in preterm infants more regular with less apneic time than that observed with theophylline. To discover whether inhalation of low CO2 decreases apneas, particularly prolonged apneas (>20 seconds), more effectively than theophylline. To discover whether short term (during hospitalization) and long term (2 years) adverse side effects are less pronounced with CO2 than with theophylline.

Conditions
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Apnea of Prematurity

Intervention / Treatment
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* Other: CO2 inhalation
* Drug: Theophylline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants between 27 and 32 weeks gestational age hospitalized in the neonatal intensive or intermediate care units Significant apnea, defined as 5 or more self-resolved apneas, or 2 or more apneas requiring intervention over a 12 hr period Exclusion Criteria: Already on methylxanthine treatment On supplemental oxygen, nasal continuous positive airway pressure (CPAP) Had major congenital anomalies, sepsis, or other known causes of apnea

Ages Eligible for Study
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Minimum Age: 27 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Theophylline<br>Oral loading dose of 6 mg per kilogram of body weight of theophylline followed by a maintenance dose of 2 mg per kilogram every 8 hours plus room air by nasal prongs at 0.5 l/min for 3 days. | Drug: Theophylline<br> <br> |
| Experimental: CO2 inhalation<br>Equivalent loading and maintenance volume of oral normal saline plus CO2 (3% at the source, approximately 1% inhaled) with room air by nasal prongs at 0.5 l/min for 3 days | Other: CO2 inhalation<br>* Inhalation of CO2 (3% at the source, approximately 1% inhaled) with room air by nasal prongs at 0.5 l/min for 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The decrease in total apnea time (duration of all apneic pauses ≥ 5 seconds) during administration of theophylline and carbon dioxide. |  | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in the rate of long apneas (≥ 20 seconds) and the incidence of short term side effects |  | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apnea, premature, infant, prematurity