CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

NCT ID: NCT01066728

Last Updated: 2010-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-08-31
• Study Completion Date: 2007-03-31

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

1. 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.

2. To discover whether inhalation of low CO2 decreases apneas, particularly prolonged apneas (>20 seconds), more effectively than theophylline.

3. To discover whether short term (during hospitalization) and long term (2 years) adverse side effects are less pronounced with CO2 than with theophylline.

Conditions

Apnea of Prematurity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Theophylline

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

CO2 inhalation

Intervention Type: OTHER

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

Interventions

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

Intervention Type: OTHER

Theophylline

Intervention Type: DRUG

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

• Minimum Eligible Age: 27 Weeks
• Maximum Eligible Age: 32 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

The Children's Hospital Foundation of Manitoba

UNKNOWN

Sponsor Role: collaborator

University of Manitoba

OTHER

Sponsor Role: lead

Responsible Party

University of Manitoba

Principal Investigators

Ruben E Alvaro, MD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

St Boniface General Hospital

Winnipeg, Manitoba, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 18534618 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11339662 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17989382 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16707748 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 3292249 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11283304 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9074983 (View on PubMed)

Other Identifiers

E98:242

Identifier Type: -

Identifier Source: org_study_id