Caffeine to Reduce Mechanical Ventilation in Preterm Infants

May 17, 2017 updated by: Eduardo Bancalari, University of Miami

Use of Caffeine to Reduce Length of Mechanical Ventilation in Preterm Infants

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • NICU, Holtz Children's Hospital, Jackson Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 5 days (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Caffeine Arm
Subjects randomized to this arm will receive blinded Caffeine citrate.
Drug: Caffeine citrate

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.
PLACEBO_COMPARATOR: Placebo Arm
Subjects randomized to this arm will receive blinded Placebo (equivalent volume of normal saline).
Other: Normal saline

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Age at First Successful Extubation
Time Frame: From birth to until 36 weeks postmenstrual age
Defined as age of extubation with infant remaining extubated for more than 24 hours.
From birth to until 36 weeks postmenstrual age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death
From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death
Total Duration of Mechanical Ventilation
Time Frame: From the time of first intubation until the last extubation, up to 36 weeks corrected age
From the time of first intubation until the last extubation, up to 36 weeks corrected age
Total Duration of Oxygen Supplementation
Time Frame: From the time of first initiation until the last day of oxygen supplementation, up to 36 weeks corrected age
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)
Time Frame: Evaluated at 36 weeks corrected postmenstrual age
BPD defined as need for oxygen for at least 28 days and at 36 weeks post-menstrual age.
Evaluated at 36 weeks corrected postmenstrual age
Survival Without BPD
Time Frame: From the time of randomization until 36 weeks corrected age, discharge or death
Discharge alive without BPD. BPD defined as need for oxygen for at least 28 days and at 36 weeks post-menstrual age.
From the time of randomization until 36 weeks corrected age, discharge or death

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Infants With Pulmonary Hemorrhage
Time Frame: From enrollment until 36 weeks postmenstrual age, discharge or death
From enrollment until 36 weeks postmenstrual age, discharge or death
Number of Infants With Necrotizing Enterocolitis
Time Frame: From enrollment until 36 weeks postmenstrual age, discharge or death
From enrollment until 36 weeks postmenstrual age, discharge or death
Number of Infants With Septicemia
Time Frame: From enrollment until 36 weeks postmenstrual age, discharge or death
Septicemia defined as positive blood culture
From enrollment until 36 weeks postmenstrual age, discharge or death
Number of Infants With Severe Intraventricular Hemorrhage
Time Frame: From enrollment until 36 weeks postmenstrual age, discharge or death
Severe intraventricular hemorrhage defined as grade III or higher
From enrollment until 36 weeks postmenstrual age, discharge or death
Number of Infants With Severe Retinopathy of Prematurity
Time Frame: From enrollment until 36 weeks postmenstrual age, discharge or death
Severe retinopathy of prematurity defined as stage 3 or higher
From enrollment until 36 weeks postmenstrual age, discharge or death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Miami

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2012

Primary Completion (ACTUAL)

January 1, 2016

Study Completion (ACTUAL)

January 1, 2016

Study Registration Dates

First Submitted

December 12, 2012

First Submitted That Met QC Criteria

December 17, 2012

First Posted (ESTIMATE)

December 18, 2012

Study Record Updates

Last Update Posted (ACTUAL)

June 19, 2017

Last Update Submitted That Met QC Criteria

May 17, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20120786

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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