CO2 Inhalation as a New Treatment Modality for Apnea of Prematurity

Apnea of Prematurity Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01066728
• Other study ID #: E98:242
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: February 9, 2010
• Last updated: March 1, 2010
• Start date: August 2001
• Est. completion date: March 2007

Study information

• Verified date: January 2010
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: March 2007
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 27 Weeks to 32 Weeks

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea of Prematurity
• Premature Birth

Intervention

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

Drug:
• Theophylline

Locations

Country	Name	City	State
Canada	Health Sciences Centre	Winnipeg	Manitoba
Canada	St Boniface General Hospital	Winnipeg	Manitoba

Sponsors (3)

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

Country where clinical trial is conducted

Canada, 

References & Publications (7)

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. — View 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. — View 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. — View Citation

Dunwiddie TV, Masino SA. The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci. 2001;24:31-55. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The decrease in total apnea time (duration of all apneic pauses = 5 seconds) during administration of theophylline and carbon dioxide.		3 days	No
Secondary	Decrease in the rate of long apneas (= 20 seconds) and the incidence of short term side effects		3 days	Yes