Caffeine to Reduce Mechanical Ventilation in Preterm Infants

NCT ID: NCT01751724

Last Updated: 2017-06-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2016-01-31

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.

Conditions

Prematurity; Apnea; Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Caffeine Arm

Subjects randomized to this arm will receive blinded Caffeine citrate.

Group Type: EXPERIMENTAL

Caffeine citrate

Intervention Type: DRUG

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 Arm

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

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 5 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Eduardo Bancalari

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eduardo Bancalari, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Nelson Claure, M.Sc., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

NICU, Holtz Children's Hospital, Jackson Health System

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29519541 (View on PubMed)

Other Identifiers

20120786

Identifier Type: -

Identifier Source: org_study_id