Caffeine to Reduce Mechanical Ventilation in Preterm Infants

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Eduardo Bancalari, University of Miami
ClinicalTrials.gov Identifier:
NCT01751724
First received: December 12, 2012
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Prematurity
Apnea
Respiratory Failure
Drug: Caffeine citrate
Other: Normal saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Use of Caffeine to Reduce Length of Mechanical Ventilation in Preterm Infants

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Time to first elective extubation [ Time Frame: From the time of first intubation until the first elective extubation, up to 36 weeks corrected age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival [ Time Frame: From the time of randomization up to 36 weeks corrected age, or until the time of discharge or death ] [ Designated as safety issue: Yes ]
  • Total duration of mechanical ventilation [ Time Frame: From the time of first intubation until the last extubation, up to 36 weeks corrected age ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Bronchopulmonary dysplasia (BPD) [ Time Frame: Evaluated at 36 weeks corrected postmenstrual age ] [ Designated as safety issue: No ]
    BPD defined as oxygen dependence at 36 weeks post-menstrual age and by physiological test, severe BPD defined as requirement for oxygen FiO2 > 0.3 at 36 weeks post menstrual age or need for positive pressure support.

  • Survival without BPD [ Time Frame: From the time of randomization until 36 weeks corrected age, discharge or death ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: December 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   up to 5 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01751724

Contacts
Contact: Eduardo Bancalari, M.D. 3055856408 ebancalari@miami.edu
Contact: Carmen Dugard, R.R.T. 3055856408 cdugard@med.miami.edu

Locations
United States, Florida
NICU, Holtz Children's Hospital, Jackson Health System Recruiting
Miami, Florida, United States, 33136
Contact: Carmen D'Ugard, R.R.T.    305-585-6408    cdugard@med.miami.edu   
Principal Investigator: Eduardo Bancalari, M.D.         
Principal Investigator: Nelson Claure, M.Sc., Ph.D.         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Eduardo Bancalari, M.D. University of Miami
Principal Investigator: Nelson Claure, M.Sc., Ph.D. University of Miami
  More Information

No publications provided

Responsible Party: Eduardo Bancalari, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT01751724     History of Changes
Other Study ID Numbers: 20120786
Study First Received: December 12, 2012
Last Updated: May 7, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Keywords provided by University of Miami:
Premature infants
Caffeine
Methylxanthines
Mechanical ventilation
Oxygen
Weaning
Bronchopulmonary dysplasia

Additional relevant MeSH terms:
Caffeine
Caffeine citrate
Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Central Nervous System Agents
Central Nervous System Stimulants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014