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

NCT01911182 | Terminated Phase 2

• 1 other identifier: B2011:072
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Apnea of Prematurity

Keywords

apnea of prematurity; control of breathing; newborn; CO2 inhalation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Effect of low concentration of CO2 on apneic time in seconds per hour and duration of long apneas in seconds

  3 hours

Study Arms (2)

Inhalation of low concentration of CO2

EXPERIMENTAL

Other: Inhalation of low concentration of CO2

caffeine only

ACTIVE COMPARATOR

Other: Inhalation of low concentration of CO2

Interventions

Inhalation of low concentration of CO2 OTHER

Inhalation of 1% CO2 through nasal prongs

Also known as: Inhalatio of biological gas

Inhalation of low concentration of CO2; caffeine only

Eligibility Criteria

• Age: 3 Days - 60 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• on mechanical ventilation
• presence of congenital anomalies, sepsis or other known causes of apnea
• failure to obtain parental consent

Sponsors & Collaborators

• University of Manitoba: lead
• Manitoba Institute of Child Health: collaborator

Study Sites (1)

University of Manitoba

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

• 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.

  PMID: 21907349 BACKGROUND

• 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. No abstract available.

  PMID: 21377992 BACKGROUND

• 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.

  PMID: 19926098 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

MeSH Terms

Conditions

Apnea

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ruben E Alvaro, MD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: July 30, 2013
• Study Start: October 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2014
• Last Updated: February 19, 2015

Record last verified: 2015-02

Locations

CA (1)