Inhalation of Low Concentration of CO2 in Preterm Infants Not Responding to Caffeine for the Treatment of Apnea

Apnea of Prematurity Clinical Trial

Official title:

A Prospective, Controlled Trial of Inhalation of Low Concentration of CO2 in Preterm Infants Not Responding to Caffeine for the Treatment of Apnea of Prematurity

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01911182
• Other study ID #: B2011:072
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: September 22, 2011
• Last updated: February 18, 2015
• Start date: October 2011
• Est. completion date: July 2014

Study information

• Verified date: February 2015
• Source: University of Manitoba
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

In premature infants, apnea of prematurity is one of their major clinical problems. Caffeine is currently a worldwide therapy to reduce the number and severity of these apneas. This practice has shown to be safe on cognitive and neurodevelopmental outcomes at 18 to 21 months of age. However, caffeine is not 100% effective, and may have little effect on hypoxemia and bradycardia. Infants with intractable apneas unresponsive to caffeine treatment may require endotracheal intubation and mechanical ventilation. This procedure is invasive and has been associated with complications and increased risk for chronic lung disease and adverse neurodevelopmental outcome. Therefore, an alternative treatment modality would be preferable if it would prevent the infants from requiring endotracheal intubation. The investigators have been testing the overall hypothesis that small concentrations of inhaled CO2 (~1%) are effective in treating apnea of prematurity. The investigators have completed three studies in preterm infants showing that inhalation of low concentration of CO2, in infants not on caffeine, regularize breathing and decrease apneas significantly. The effects of inhalation of CO2 in infants already on caffeine, are unknown. The hypothesis to be tested is that inhalation of low concentration CO2 (1%) will significantly reduce apnea in infants treated with caffeine. The investigators have three specific aims in this proposal. 1) the investigators want to know if the apnea rate (number of apneas of ≥5 seconds/hour) is decreased with CO2 inhalation in preterm infants already on caffeine for the treatment of apnea of prematurity; 2) the investigators want to know whether inhalation of CO2 can make breathing more regular with less apneic time and whether it decreases prolonged apneas (>20 seconds) in infants already on caffeine for the treatment of apnea of prematurity; 3) the investigators want to assess the effect of inhalation of low concentration of CO2 on the regional oxygen saturation of the brain measured by near-infrared spectroscopy (NIRS) during apneas. This is to see whether CO2, by protecting cerebral blood flow, minimizes the decrease in cerebral oxygenation during apneas. This study entails a new and possibly more physiological method of treating apneas of prematurity that can be added to the present treatment of caffeine. These two treatments together, could minimize the number and severity of apneas and possibly decrease the need for mechanical ventilation in preterm infants.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: July 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 60 Days

Eligibility

Inclusion Criteria:

• gestational age at birth < 33 weeks

• on caffeine treatment for apnea of prematurity at a maintenance dose of 5 mg/kg/day

• having apnea of prematurity (at least 5 self-resolved apneas or 2 apneas requiring intervention/12 hours)

Exclusion Criteria:

• on mechanical ventilation

• presence of congenital anomalies, sepsis or other known causes of apnea

• failure to obtain parental consent

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Apnea of Prematurity
• Premature Birth

Intervention

Other:
• Inhalation of low concentration of CO2
Inhalation of 1% CO2 through nasal prongs

Locations

Country	Name	City	State
Canada	University of Manitoba	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
University of Manitoba	Manitoba Institute of Child Health

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

Alvaro RE, Khalil M, Qurashi M, Al-Saif S, Al-Matary A, Chiu A, Minski J, Manfreda J, Kwiatkowski K, Cates D, Rigatto H. CO(2) inhalation as a treatment for apnea of prematurity: a randomized double-blind controlled trial. J Pediatr. 2012 Feb;160(2):252-257.e1. doi: 10.1016/j.jpeds.2011.07.049. Epub 2011 Sep 9. — View Citation

Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, Sinha S, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine for Apnea of Prematurity trial: benefits may vary in subgroups. J Pediatr. 2010 Mar;156(3):382-7. doi: 10.1016/j.jpeds.2009.09.069. Epub 2009 Nov 18. — 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

Schmidt B, Roberts RS, Davis P, Doyle LW; Steering Committee of the Caffeine for Apnea of Prematurity (CAP) trial. Archimedes: Does caffeine treatment for apnoea of prematurity improve neurodevelopmental outcome in later life? Arch Dis Child. 2011 Aug;96(8):784. doi: 10.1136/adc.2010.206698. Epub 2011 Mar 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of inhalation of low concentration of CO2 (1%) on the apnea rate (number of apneas of =5 seconds/hour) in preterm infants already on caffeine for the treatment of apnea of prematurity.		3 hours	Yes
Secondary	Effect of low concentration of CO2 on apneic time in seconds per hour and duration of long apneas in seconds		3 hours	No