CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

Sponsor

University of Manitoba (Other)

Overall Status

Completed

CT.gov ID

NCT01066728

Collaborator

Canadian Institutes of Health Research (CIHR) (Other), The Children's Hospital Foundation of Manitoba (Other)

Enrollment

Locations

Arms

Duration (Months)

43.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Apnea of Prematurity	Other: CO2 inhalation Drug: Theophylline	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

87 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Study Start Date :

Aug 1, 2001

Actual Primary Completion Date :

Sep 1, 2005

Actual Study Completion Date :

Mar 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Theophylline 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
Experimental: CO2 inhalation 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 Inhalation of CO2 (3% at the source, approximately 1% inhaled) with room air by nasal prongs at 0.5 l/min for 3 days

Arm

Intervention/Treatment

Active Comparator: Theophylline

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

Experimental: CO2 inhalation

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

Inhalation of CO2 (3% at the source, approximately 1% inhaled) with room air by nasal prongs at 0.5 l/min for 3 days

Outcome Measures

Primary Outcome Measures

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

Decrease in the rate of long apneas (≥ 20 seconds) and the incidence of short term side effects [3 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

27 Weeks to 32 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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