CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

NCT01066728 | Completed Phase 2 DMC

• 1 other identifier: E98:242
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 2

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.

Conditions

Apnea of Prematurity

Keywords

apnea; premature; infant; prematurity

Outcome Measures

Primary Outcomes (1)

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

  3 days

Secondary Outcomes (1)

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

  3 days

Study Arms (2)

Theophylline

ACTIVE COMPARATOR

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

CO2 inhalation

EXPERIMENTAL

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

Interventions

CO2 inhalation 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

CO2 inhalation

Theophylline DRUG

Theophylline

Eligibility Criteria

• Age: 27 Weeks - 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Already on methylxanthine treatment
• On supplemental oxygen, nasal continuous positive airway pressure (CPAP)
• Had major congenital anomalies, sepsis, or other known causes of apnea

Sponsors & Collaborators

• University of Manitoba: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• The Children's Hospital Foundation of Manitoba: collaborator

Study Sites (2)

St Boniface General Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Health Sciences Centre

Winnipeg, Manitoba, R3E 0L8, Canada

Location

Related Publications (7)

• 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.

  PMID: 18534618 BACKGROUND

• 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.

  PMID: 11339662 BACKGROUND

• 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.

  PMID: 17989382 BACKGROUND

• 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.

  PMID: 16707748 BACKGROUND

• 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.

  PMID: 3292249 BACKGROUND

• 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.

  PMID: 11283304 BACKGROUND

• 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.

  PMID: 9074983 BACKGROUND

MeSH Terms

Conditions

Apnea; Premature Birth

Interventions

Theophylline

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ruben E Alvaro, MD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 9, 2010
• First Posted: February 10, 2010
• Study Start: August 1, 2001
• Primary Completion: September 1, 2005
• Study Completion: March 1, 2007
• Last Updated: March 3, 2010

Record last verified: 2010-01

Locations

CA (2)