Clinical trial NCT01066728: CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Apnea of Prematurity
Keywords: apnea
premature
infant
prematurity
Lead sponsor: University of Manitoba
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: The Children's Hospital Foundation of Manitoba
First posted: 2010-02-10
Enrollment: 87
Sex: ALL
Minimum age (years): 27
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The decrease in total apnea time (duration of all apneic pauses ≥ 5 seconds) during administration of theophylline and carbon dioxide.
timeFrame: 3 days
Secondary outcomes:
measure: Decrease in the rate of long apneas (≥ 20 seconds) and the incidence of short term side effects
timeFrame: 3 days
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: St Boniface General Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
Study officials:
affiliation: University of Manitoba
name: Ruben E Alvaro, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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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.
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.
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.
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.