NCT01751724

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
87

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Dec 2012

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2012

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

December 12, 2012

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 18, 2012

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

June 19, 2017

Completed
Last Updated

June 19, 2017

Status Verified

May 1, 2017

Enrollment Period

3.1 years

First QC Date

December 12, 2012

Results QC Date

February 28, 2017

Last Update Submit

May 17, 2017

Conditions

Keywords

Premature infantsCaffeineMethylxanthinesMechanical ventilationOxygenWeaningBronchopulmonary dysplasia

Outcome Measures

Primary Outcomes (1)

  • Age at First Successful Extubation

    Defined as age of extubation with infant remaining extubated for more than 24 hours.

    From birth to until 36 weeks postmenstrual age

Secondary Outcomes (5)

  • Survival

    From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death

  • Total Duration of Mechanical Ventilation

    From the time of first intubation until the last extubation, up to 36 weeks corrected age

  • Total Duration of Oxygen Supplementation

    From the time of first initiation until the last day of oxygen supplementation, up to 36 weeks corrected age

  • Number of Infants With Bronchopulmonary Dysplasia (BPD)

    Evaluated at 36 weeks corrected postmenstrual age

  • Survival Without BPD

    From the time of randomization until 36 weeks corrected age, discharge or death

Other Outcomes (5)

  • Number of Infants With Pulmonary Hemorrhage

    From enrollment until 36 weeks postmenstrual age, discharge or death

  • Number of Infants With Necrotizing Enterocolitis

    From enrollment until 36 weeks postmenstrual age, discharge or death

  • Number of Infants With Septicemia

    From enrollment until 36 weeks postmenstrual age, discharge or death

  • +2 more other outcomes

Study Arms (2)

Caffeine Arm

EXPERIMENTAL

Subjects randomized to this arm will receive blinded Caffeine citrate.

Drug: Caffeine citrate

Placebo Arm

PLACEBO COMPARATOR

Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline).

Other: Normal saline

Interventions

Enrolled subjects will be randomized to receive a study drug consisting of either blinded Caffeine citrate. Randomization and study drug preparation will be done by the NICU pharmacy. Investigators and clinicians will be blinded to the assigned drug. After randomization, an initial loading dose of 20 mg/Kg of study drug will be followed by a 5 mg/Kg/day maintenance dose. The assigned study drug will be administered intravenous or orally as determined by the clinical team. Infants will continue to receive the study drug until 12 hours prior to the first elective extubation.

Caffeine Arm

Enrolled subjects will be randomized to receive a study drug consisting of blinded Placebo (equivalent volume of normal saline). Randomization and study drug preparation will be done by the NICU pharmacy. Investigators and clinicians will be blinded to the assigned drug. After randomization, an initial loading dose of 20 mg/Kg of study drug will be followed by a 5 mg/Kg/day maintenance dose. The assigned study drug will be administered intravenous or orally as determined by the clinical team. Infants will continue to receive the study drug until 12 hours prior to the first elective extubation.

Placebo Arm

Eligibility Criteria

Age1 Day - 5 Days
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • Major congenital anomalies
  • Small for gestational age

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

NICU, Holtz Children's Hospital, Jackson Health System

Miami, Florida, 33136, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Premature BirthApneaRespiratory InsufficiencyBronchopulmonary Dysplasia

Interventions

caffeine citrateSaline Solution

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesRespiration DisordersRespiratory Tract DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsVentilator-Induced Lung InjuryLung InjuryLung DiseasesInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Results Point of Contact

Title
Eduardo Bancalari M.D., Director Division of Neonatology
Organization
University of Miami

Study Officials

  • Eduardo Bancalari, M.D.

    University of Miami

    PRINCIPAL INVESTIGATOR
  • Nelson Claure, M.Sc., Ph.D.

    University of Miami

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

December 12, 2012

First Posted

December 18, 2012

Study Start

December 1, 2012

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

June 19, 2017

Results First Posted

June 19, 2017

Record last verified: 2017-05

Locations