Caffeine for Apnea of Prematurity (CAP)

Summary

At least 5 of every 1000 live-born babies are very premature and weigh only 500 to 1250 grams at birth. Approximately 30-40% of these high-risk infants either die or survive with lasting disabilities. The aim of this research is to reduce this heavy burden of illness. A multi-center randomized controlled trial has been designed in which 2000 very low birth weight infants will be enrolled. Our goal is to determine whether the avoidance of methylxanthine drugs will improve survival without disability to 18 months, corrected for prematurity. Methylxanthine drugs such as caffeine are used to prevent or treat periodic breathing and breath-holding spells in premature infants. However, there is a striking lack of evidence for the long-term efficacy and safety of this therapy. Methylxanthines block a naturally occurring substance, called adenosine, which protects the brain during episodes of oxygen deficiency. Such episodes are common in infants who are treated with methylxanthines. It is possible that methylxanthines may worsen the damage caused by lack of oxygen. Therefore, this trial will clarify whether methylxanthines cause more good than harm in very low birth weight infants.

Timeline

Start

1999-10

Primary completion

2007-03

Completion

2016-07

Publications

• Results 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.
• Results 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.
• Results 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.
• Results Schmidt B, Anderson PJ, Doyle LW, Dewey D, Grunau RE, Asztalos EV, Davis PG, Tin W, Moddemann D, Solimano A, Ohlsson A, Barrington KJ, Roberts RS; Caffeine for Apnea of Prematurity (CAP) Trial Investigators. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA. 2012 Jan 18;307(3):275-82. doi: 10.1001/jama.2011.2024.
• Results Dukhovny D, Lorch SA, Schmidt B, Doyle LW, Kok JH, Roberts RS, Kamholz KL, Wang N, Mao W, Zupancic JA; Caffeine for Apnea of Prematurity Trial Group. Economic evaluation of caffeine for apnea of prematurity. Pediatrics. 2011 Jan;127(1):e146-55. doi: 10.1542/peds.2010-1014. Epub 2010 Dec 20.
• Results Schmidt B, Davis PG, Asztalos EV, Solimano A, Roberts RS. Association between severe retinopathy of prematurity and nonvisual disabilities at age 5 years. JAMA. 2014 Feb 5;311(5):523-5. doi: 10.1001/jama.2013.282153. No abstract available.
• Results Doyle LW, Schmidt B, Anderson PJ, Davis PG, Moddemann D, Grunau RE, O'Brien K, Sankaran K, Herlenius E, Roberts R; Caffeine for Apnea of Prematurity Trial investigators. Reduction in developmental coordination disorder with neonatal caffeine therapy. J Pediatr. 2014 Aug;165(2):356-359.e2. doi: 10.1016/j.jpeds.2014.04.016. Epub 2014 May 17.
• Doyle LW, Ranganathan S, Cheong JLY. Neonatal Caffeine Treatment and Respiratory Function at 11 Years in Children under 1,251 g at Birth. Am J Respir Crit Care Med. 2017 Nov 15;196(10):1318-1324. doi: 10.1164/rccm.201704-0767OC.
• Schmidt B, Roberts RS, Anderson PJ, Asztalos EV, Costantini L, Davis PG, Dewey D, D'Ilario J, Doyle LW, Grunau RE, Moddemann D, Nelson H, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity (CAP) Trial Group. Academic Performance, Motor Function, and Behavior 11 Years After Neonatal Caffeine Citrate Therapy for Apnea of Prematurity: An 11-Year Follow-up of the CAP Randomized Clinical Trial. JAMA Pediatr. 2017 Jun 1;171(6):564-572. doi: 10.1001/jamapediatrics.2017.0238.
• Synnes A, Anderson PJ, Grunau RE, Dewey D, Moddemann D, Tin W, Davis PG, Doyle LW, Foster G, Khairy M, Nwaesei C, Schmidt B; CAP Trial Investigator group. Predicting severe motor impairment in preterm children at age 5 years. Arch Dis Child. 2015 Aug;100(8):748-53. doi: 10.1136/archdischild-2014-307695. Epub 2015 Mar 17.
• Manley BJ, Roberts RS, Doyle LW, Schmidt B, Anderson PJ, Barrington KJ, Bohm B, Golan A, van Wassenaer-Leemhuis AG, Davis PG; Caffeine for Apnea of Prematurity (CAP) Trial Investigators; Caffeine for Apnea of Prematurity CAP Trial Investigators. Social variables predict gains in cognitive scores across the preschool years in children with birth weights 500 to 1250 grams. J Pediatr. 2015 Apr;166(4):870-6.e1-2. doi: 10.1016/j.jpeds.2014.12.016. Epub 2015 Jan 29.

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