Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants

A Randomized, Placebo-Controlled Trial

Cynthia M. Amaro, Jose A. Bello, Deepak Jain, Alexandra Ramnath, Carmen D'Ugard, Silvia Vanbuskirk, Eduardo Bancalari, Nelson R Claure

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Study design: Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Results: Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P =.7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P =.22). Conclusions: Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. Trial Registration: ClinicalTrials.gov NCT01751724.

Original languageEnglish (US)
JournalJournal of Pediatrics
DOIs
StateAccepted/In press - Jan 1 2018

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Caffeine
Artificial Respiration
Premature Infants
Randomized Controlled Trials
Placebos
Mortality
Clinical Trials Data Monitoring Committees
Control Groups
Safety
Pregnancy

Keywords

  • caffeine citrate
  • extubation
  • premature infant
  • weaning

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants : A Randomized, Placebo-Controlled Trial. / Amaro, Cynthia M.; Bello, Jose A.; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson R.

In: Journal of Pediatrics, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Objective: To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Study design: Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Results: Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P =.7). An interim analysis at 75{\%} enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22{\%}]) and control groups (5 [12{\%}]; P =.22). Conclusions: Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. Trial Registration: ClinicalTrials.gov NCT01751724.",
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AU - Ramnath, Alexandra

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AB - Objective: To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Study design: Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Results: Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P =.7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P =.22). Conclusions: Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. Trial Registration: ClinicalTrials.gov NCT01751724.

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