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CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

Primary Purpose

Apnea of Prematurity

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

CO2 inhalation

Theophylline

About this trial

This is an interventional treatment trial for Apnea of Prematurity focused on measuring apnea, premature, infant, prematurity

Eligibility Criteria

27 Weeks - 32 Weeks (Child)All SexesDoes not accept 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

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

Sites / Locations

St Boniface General Hospital
Health Sciences Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Theophylline

CO2 inhalation

Arm Description

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.

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

Outcomes

Primary Outcome Measures

The decrease in total apnea time (duration of all apneic pauses ≥ 5 seconds) during administration of theophylline and carbon dioxide.

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01066728

First Posted

February 9, 2010

Last Updated

March 1, 2010

Sponsor

University of Manitoba

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01066728

Brief Title

CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

Study Type

Interventional

2. Study Status

Record Verification Date

January 2010

Overall Recruitment Status

Completed

Study Start Date

August 2001 (undefined)

Primary Completion Date

September 2005 (Actual)

Study Completion Date

March 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

University of Manitoba

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Apnea of Prematurity

Keywords

apnea, premature, infant, prematurity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

87 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Theophylline

Arm Type

Active Comparator

Arm Description

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.

Arm Title

CO2 inhalation

Arm Type

Experimental

Arm Description

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

Intervention Type

Other

Intervention Name(s)

CO2 inhalation

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Theophylline

Primary Outcome Measure Information:

Title

The decrease in total apnea time (duration of all apneic pauses ≥ 5 seconds) during administration of theophylline and carbon dioxide.

Time Frame

3 days

Secondary Outcome Measure Information:

Title

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

Time Frame

3 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

27 Weeks

Maximum Age & Unit of Time

32 Weeks

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ruben E Alvaro, MD

Organizational Affiliation

University of Manitoba

Official's Role

Principal Investigator

Facility Information:

Facility Name

St Boniface General Hospital

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R2H 2A6

Country

Canada

Facility Name

Health Sciences Centre

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3E 0L8

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

18534618

Citation

Al-Saif S, Alvaro R, Manfreda J, Kwiatkowski K, Cates D, Qurashi M, Rigatto H. A randomized controlled trial of theophylline versus CO2 inhalation for treating apnea of prematurity. J Pediatr. 2008 Oct;153(4):513-8. doi: 10.1016/j.jpeds.2008.04.025. Epub 2008 Jun 4.

Results Reference

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PubMed Identifier

11339662

Citation

Al-Aif S, Alvaro R, Manfreda J, Kwiatkowski K, Cates D, Rigatto H. Inhalation of low (0.5%-1.5%) CO2 as a potential treatment for apnea of prematurity. Semin Perinatol. 2001 Apr;25(2):100-6. doi: 10.1053/sper.2001.23199.

Results Reference

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PubMed Identifier

17989382

Citation

Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med. 2007 Nov 8;357(19):1893-902. doi: 10.1056/NEJMoa073679.

Results Reference

background

PubMed Identifier

16707748

Citation

Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.

Results Reference

background

PubMed Identifier

3292249

Citation

Bucher HU, Duc G. Does caffeine prevent hypoxaemic episodes in premature infants? A randomized controlled trial. Eur J Pediatr. 1988 Apr;147(3):288-91. doi: 10.1007/BF00442697.

Results Reference

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PubMed Identifier

11283304

Citation

Dunwiddie TV, Masino SA. The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci. 2001;24:31-55. doi: 10.1146/annurev.neuro.24.1.31.

Results Reference

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PubMed Identifier

9074983

Citation

Xie A, Rankin F, Rutherford R, Bradley TD. Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea. J Appl Physiol (1985). 1997 Mar;82(3):918-26. doi: 10.1152/jappl.1997.82.3.918.

Results Reference

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CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

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