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
|Condition or disease||Intervention/treatment||Phase|
|BPD - Bronchopulmonary Dysplasia Apnea of Prematurity Hemodynamic Instability Intubation||Drug: Caffeine Citrate Drug: Placebo (Normal Saline)||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||88 participants|
|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.|
|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|
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
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.
- Intubation [ Time Frame: Within 12 hours of life ]Need for endotracheal intubation within the first 12 hours of life.
- 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.
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
|Contact: Jennifer L Shepherd, MD||(361) firstname.lastname@example.org|
|United States, California|
|Hollywood Presbyterian Medical Center||Not yet recruiting|
|Los Angeles, California, United States, 90027|
|Contact: Jennifer L Shepherd, MD 323-361-5939 email@example.com|
|Contact: Shahab Noori, MD (323) 361-5939 firstname.lastname@example.org|
|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 email@example.com|
|Contact: Rangasamy Ramanathan, MD (323) 226-3406 firstname.lastname@example.org|
|Principal Investigator: Jennifer L Shepherd, MD|
|Sub-Investigator: Rangasamy Ramanathan, MD|
|Principal Investigator:||Jennifer L Shepherd, MD||University of Southern California|