Clinical trial NCT01751724: Caffeine to Reduce Mechanical Ventilation in Preterm Infants
Official title: Use of Caffeine to Reduce Length of Mechanical Ventilation in Preterm Infants
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Prematurity
Apnea
Respiratory Failure
Keywords: Premature infants
Caffeine
Methylxanthines
Mechanical ventilation
Oxygen
Weaning
Bronchopulmonary dysplasia
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2012-12-18
Enrollment: 87
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Most premature infants require mechanical ventilation for prolonged periods of time and a significant proportion of them develop Bronchopulmonary Dysplasia (BPD). Caffeine is a stimulant of the respiratory center and has been used for the treatment of Apnea of Prematurity in infants not requiring mechanical ventilation or to facilitate weaning from mechanical ventilation by starting therapy shortly before extubation. Recently the use of Caffeine in ventilated infants has been initiated earlier because of the reported reduction in BPD. However there is paucity of data supporting this practice.

Because protracted mechanical ventilation and supplemental oxygen increase the risk of developing BPD, a therapy that would facilitate the reduction of the respiratory support and shorten its duration is desirable. Therefore, it is of importance to evaluate the effects of early Caffeine initiation and administration during the course of mechanical ventilation in preterm infants by means of a randomized placebo-controlled trial.

Hypothesis:

The primary hypothesis of this study is that early use of caffeine in mechanically ventilated preterm infants will reduce the time to first elective extubation and secondarily, that this will reduce the total duration of mechanical ventilation and oxygen supplementation, and reduce the incidence and severity of BPD.

Objective:

The objective of this trial is to evaluate the effects of early caffeine use during mechanical ventilation on the time to first elective extubation, total duration of mechanical ventilation and oxygen supplementation, and the incidence of BPD.

Study Design:

This will be a single-center prospective, randomized, double-blind, placebo controlled clinical trial.

Population:

Premature neonates born between 23 and 30 completed weeks of gestation, who require mechanical ventilation within the first 5 days of life will be enrolled. Infants with major congenital anomalies or small for gestational age will be excluded.

Methods:

Infants will be randomized within the first 5 days to receive a study drug consisting of either blinded Caffeine citrate or blinded Placebo (equivalent volume of normal saline). Infants will continue to receive the study drug until the first elective extubation.


Eligibility criteria: Inclusion Criteria:

* Premature neonates born between 23 and 30 completed weeks of gestation.
* Requiring mechanical ventilation within the first 5 postnatal days
* Written-informed parental consent for the study

Exclusion Criteria:

* Major congenital anomalies
* Small for gestational age

Primary outcomes:
measure: Age at First Successful Extubation
timeFrame: From birth to until 36 weeks postmenstrual age
Secondary outcomes:
measure: Survival
timeFrame: From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death
measure: Total Duration of Mechanical Ventilation
timeFrame: From the time of first intubation until the last extubation, up to 36 weeks corrected age
measure: Total Duration of Oxygen Supplementation
timeFrame: From the time of first initiation until the last day of oxygen supplementation, up to 36 weeks corrected age
measure: Number of Infants With Bronchopulmonary Dysplasia (BPD)
timeFrame: Evaluated at 36 weeks corrected postmenstrual age
measure: Survival Without BPD
timeFrame: From the time of randomization until 36 weeks corrected age, discharge or death
Other outcomes:
measure: Number of Infants With Pulmonary Hemorrhage
timeFrame: From enrollment until 36 weeks postmenstrual age, discharge or death
measure: Number of Infants With Necrotizing Enterocolitis
timeFrame: From enrollment until 36 weeks postmenstrual age, discharge or death
measure: Number of Infants With Septicemia
timeFrame: From enrollment until 36 weeks postmenstrual age, discharge or death
measure: Number of Infants With Severe Intraventricular Hemorrhage
timeFrame: From enrollment until 36 weeks postmenstrual age, discharge or death
measure: Number of Infants With Severe Retinopathy of Prematurity
timeFrame: From enrollment until 36 weeks postmenstrual age, discharge or death
Locations:
city: Miami
country: United States
facility: NICU, Holtz Children's Hospital, Jackson Health System
state: Florida
Study officials:
affiliation: University of Miami
name: Eduardo Bancalari, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Nelson Claure, M.Sc., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amaro CM, Bello JA, Jain D, Ramnath A, D'Ugard C, Vanbuskirk S, Bancalari E, Claure N. Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial. J Pediatr. 2018 May;196:52-57. doi: 10.1016/j.jpeds.2018.01.010. Epub 2018 Mar 6.