Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Early Caffeine in Preterm Neonates

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03086473
Recruitment Status : Recruiting
First Posted : March 22, 2017
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
The Gerber Foundation
Information provided by (Responsible Party):
Jennifer Shepherd, Children's Hospital Los Angeles

Brief Summary:
This is a clinical trial which will investigate whether administration of caffeine, a respiratory stimulant, to preterm babies soon after birth can prevent the need for a breathing tube, or intubation. Many preterm babies who require intubation are intubated soon after birth, often within the first few hours. If caffeine is given early enough and is sufficient to stimulate effective breathing, perhaps these babies may not require intubation. Additionally, caffeine may improve blood flow in preterm babies when given soon after birth. Approximately half of babies in this study will receive caffeine within two hours after birth, and half will receive caffeine 12 hours after birth. The hypothesis is that preterm babies who receive caffeine within 2 hours after birth will have a lower incidence of intubation than preterm babies who receive caffeine 12 hours after birth. The main secondary hypothesis is that caffeine given soon after birth will enhance blood flow in preterm babies.

Condition or disease Intervention/treatment Phase
BPD - Bronchopulmonary Dysplasia Apnea of Prematurity Hemodynamic Instability Intubation Drug: Caffeine Citrate Drug: Placebo (Normal Saline) Phase 4

Detailed Description:

Caffeine is routinely administered to extremely preterm neonates as a respiratory stimulant to prevent or treat apnea of prematurity, or prolonged pauses in breathing in preterm babies. Caffeine, a methylxanthine, is an adenosine receptor antagonist that has the effects of relaxing smooth muscle in the airways, stimulating the central nervous system and cardiac muscle, and acting as a diuretic. The mode of action in apnea of prematurity could be from several mechanisms, including stimulation of respiratory drive, enhancement of minute ventilation, increased response to hypercapnia, increase in skeletal muscle tone, and decrease in diaphragmatic fatigue.

The timing of caffeine administration is highly variable, ranging from the first hours of life to several days after birth. In the Caffeine for Apnea of Prematurity (CAP) trial, in which the average day of initial caffeine dose was 3 days of life, the incidence of bronchopulmonary dysplasia (BPD) was significantly reduced in the caffeine group compared to the placebo group (47% vs 36%, p<0.001). Neonates in the caffeine group also had fewer days of mechanical ventilation and oxygen exposure, both of which are known risk factors in the development of BPD. Further studies have demonstrated greater benefit of caffeine given in the first 2-3 days of life versus later. These studies suggest that caffeine administered earlier in life may be beneficial in terms of respiratory outcomes. However, the effects of caffeine administered shortly after birth are unknown and need to be studied with a randomized, placebo-controlled trial.

The investigators postulate that by giving caffeine as soon as possible after birth, intrinsic respiratory function will be supported sufficiently to avoid intubation altogether, thus eliminating a major risk factor for BPD. Intravenous caffeine reaches therapeutic level almost immediately, typically within thirty minutes of administration. However, the majority of infants who require invasive ventilation are intubated within the first few hours of life, usually before the infant has received caffeine. Additionally, many centers utilize minimally invasive administration of surfactant, a medication that helps keep lungs open by lowering surface tension, to treat respiratory distress syndrome of the newborn in attempt to avoid intubation, as preterm neonates who do not require immediate intubation and instead receive non-invasive continuous positive airway pressure (CPAP) at birth have decreased risk of BPD. These techniques require spontaneous, effective breathing, and early caffeine administration may aid in this process. This study aims to deliver caffeine to preterm infants immediately after birth to determine whether intubation can be avoided.

While the primary outcome of this study is aimed at reducing intubation rates and thus affecting rates of BPD, beneficial cardiovascular effects may also be noted. The incidence of hypotension in preterm infants <28 weeks is as high as 78%.This study will also be using non-invasive technologies to continuously monitor hemodynamic parameters including cardiac function, output, blood flow, oxygenation to the brain surrounding the administration of caffeine. Very early caffeine therapy may improve cardiovascular function in this early transitional period, potentially decreasing the risk of devastating complications of prematurity such as intraventricular hemorrhage.

This is a double-blinded, randomized, placebo-controlled clinical trial which will investigate whether administration of caffeine to preterm neonates (<32 weeks' gestation) within the first 2 hours of life compared to 12 hours of life will decrease the rate of intubation during the first 12 hours of life. This study will also investigate whether caffeine administration to preterm neonates (<32 weeks' gestation) increases cardiac output. A total of 88 infants will be included in this study, randomized to two study arms. One arm will receive intravenous caffeine citrate within 2 hours of life and placebo (normal saline) at 12 hours of life, and the other arm will receive placebo within 2 hours of life and caffeine citrate at 12 hours of life. Therefore, all participants will receive caffeine by 12 hours of life, and the only variable is the timing of caffeine.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Each participant is assigned to one of two arms of the study.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The participant and participant's parents, medical care providers, and investigators will remain masked to the randomization.
Primary Purpose: Prevention
Official Title: A Randomized, Placebo-controlled Trial of Early Caffeine in Preterm Neonates
Actual Study Start Date : February 1, 2017
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Caffeine

Arm Intervention/treatment
Caffeine
Participant will receive caffeine citrate 20mg/kg IV within 2 hours of life and placebo (normal saline IV) at 12 hours of life. Both infusions will be of identical volumes and appearance, and will be administered over 30 minutes.
Drug: Caffeine Citrate
The intervention in this study is timing of the initial caffeine dose. In the Caffeine arm, participants will receive Caffeine Citrate 20mg/kg IV (volume dose 1ml/kg) within 2 hours of life, and Normal Saline (0.9% NaCl) 1ml/kg IV at 12 hours of life.
Other Name: Cafcit

Placebo
Participant will receive placebo (normal saline IV) within 2 hours of life and caffeine citrate 20mg/kg IV at 12 hours of life. Both infusions will be of identical volumes and appearance, and will be administered over 30 minutes.
Drug: Placebo (Normal Saline)
The intervention in this study is timing of the initial caffeine dose. In the Placebo arm, participants will receive Normal Saline (0.9%NaCl) 1ml/kg IV within 2 hours of life, and Caffeine Citrate 20mg/kg IV (volume dose 1ml/kg) at 12 hours of life.




Primary Outcome Measures :
  1. Intubation [ Time Frame: Within 12 hours of life ]
    Need for endotracheal intubation within the first 12 hours of life.


Secondary Outcome Measures :
  1. Cardiac output [ Time Frame: Prior to and 1 hour after receipt of caffeine/placebo at 2 hours of life and 12 hours of life ]
    Changes in cardiac output after administration of caffeine.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 1 Day   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Neonates <32 weeks' gestational age born at LAC+USC Medical Center, Hollywood Presbyterian Medical Center, or other sites affiliated with USC or CHLA will be considered for enrollment.

Exclusion Criteria:

  • Exclusions are major congenital anomalies, major cardiac defects (other than patent ductus arteriosus, patent foramen ovale, small atrial septal defect, and small ventricular septal defect), and intubation in the delivery room
  • If intravenous access is not obtained within the first 2 hours of life (either through peripheral IV or central venous catheter), then the neonate will no longer be eligible for the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03086473


Contacts
Layout table for location contacts
Contact: Jennifer L Shepherd, MD (361) 323-5939 jeshepherd@chla.usc.edu

Locations
Layout table for location information
United States, California
Hollywood Presbyterian Medical Center Not yet recruiting
Los Angeles, California, United States, 90027
Contact: Jennifer L Shepherd, MD    323-361-5939    jeshepherd@chla.usc.edu   
Contact: Shahab Noori, MD    (323) 361-5939    snoori@chla.usc.edu   
Principal Investigator: Jennifer L Shepherd, MD         
Sub-Investigator: Shahab Noori, MD, MS CBTI         
LAC+USC Medical Center Recruiting
Los Angeles, California, United States, 90033
Contact: Jennifer L Shepherd, MD    323-226-3406    jeshepherd@chla.usc.edu   
Contact: Rangasamy Ramanathan, MD    (323) 226-3406    ramanath@usc.edu   
Principal Investigator: Jennifer L Shepherd, MD         
Sub-Investigator: Rangasamy Ramanathan, MD         
Sponsors and Collaborators
Jennifer Shepherd
The Gerber Foundation
Investigators
Layout table for investigator information
Principal Investigator: Jennifer L Shepherd, MD University of Southern California

Publications:

Layout table for additonal information
Responsible Party: Jennifer Shepherd, Assistant Professor of Clinical Pediatrics, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT03086473     History of Changes
Other Study ID Numbers: HS-15-00899
First Posted: March 22, 2017    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Jennifer Shepherd, Children's Hospital Los Angeles:
caffeine
intubation
hemodynamics
mechanical ventilation
cardiac output
near infrared spectroscopy
functional echocardiography
Additional relevant MeSH terms:
Layout table for MeSH terms
Bronchopulmonary Dysplasia
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Caffeine
Caffeine citrate
Citric Acid
Sodium Citrate
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents