The Caffeine Therapy in the Fetal to Neonatal Transition

The Caffeine Therapy in the Fetal to Neonatal Transition in Preterms

Introduction: The caffeine is used in the treatment for apnea of prematurity and it has several positive effects in the neurodevelopment of preterm babies. There are innumerable observational studies suggesting that initiating caffeine in the first hours of life may offer more benefits in the reduction of the necessity of intubation and in ventilation time. It is necessary to expand further research on the best time to start caffeine, which may improve the quality of care for premature infants.

Objective: To evaluate the benefits of caffeine administration in the first two hours of life compared to administration at 24 hours of life in premature patients on noninvasive mechanical ventilation with birth weights less than 1250 grams.

Methodology: Preterm newborn patients with birth weight < 1250 grams born at Hospital de Clínicas de Porto Alegre who are not intubated in the delivery room will be included. Patients will be randomized into two groups. One arm of the study will receive caffeine at 2 hours of age and the other arm will receive caffeine at 24 hours of age (control). Patients in the control group will receive 0.9% SF at 2 hours of life in order to keep the study blinded. The following outcomes will be evaluated: need for intubation, time on invasive and non-invasive mechanical ventilation, BPD, necrotizing enterocolitis, need for ROP treatment, PDA with hemodynamic repercussions, peri-intraventricular hemorrhage, leukomalacia and death. The sample size calculation is 50 patients, 25 in each arm.

Expected Results: It is expected to find a 43% reduction in the need for intubation in preterm infants who receive caffeine in the first two hours of life compared to administration at 24 hours of life. It is also expected to find a reduction in mechanical ventilation time, in addition to a possible reduction in negative outcomes associated with prematurity.

Study Overview

• Status: Recruiting
• Conditions: Mechanical Ventilation Complication; Caffeine; Ventilator Lung; Newborn
• Intervention / Treatment: Drug: Early Caffeine administration; Other: Control Group

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gabriela Trindade; Phone Number: +55 51 985002009; Email: gabs.trindade@gmail.com

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre
      • Contact: Gabriela Trindade; Phone Number: +55 51 985002009; Email: gabs.trindade@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Premature newborns with birth weight less than 1250 grams who are not intubated in the delivery room, born at the Hospital de Clínicas de Porto Alegre between March 2022 and June 2023.

Exclusion Criteria:

• Premature newborns from other hospitals, with the presence of a major congenital malformation or genetic syndrome, and newborns without parental consent will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Caffeine Group; Group administering caffeine in the first 2 hours of life. Patients in the early caffeine group will receive an attack dose of caffeine 20 mg/kg and begin maintenance dose 10 mg/kg/day.	Drug: Early Caffeine administration; Blinding will be done with the administration of saline solution. Patients in the early caffeine group will receive an attack dose of caffeine 20 mg/kg and begin maintenance dose 10 mg/kg/day. Patients in the late caffeine group, receive bolus of saline solution in the first 2 hours of life, starting, at 24 hours of life, the caffeine-loading dose 20 mg/kg and after maintenance dose 10mg/kg/day. The medical team will prescribe the medication, and the pharmacy will be responsible for randomly dispensing the caffeine or saline solution. The pharmacy will prepare syringes with the medication or saline solution identified by a code referring to the randomization without identifying which solution is being administered. The syringes will be sent to the neonatal ICU and will be administered according to the physician's prescription. The administration will be blinded.
Active Comparator: Control Group; Patients in the late caffeine group, receive bolus of saline solution in the first 2 hours of life, starting, at 24 hours of life, the caffeine-loading dose 20 mg/kg and after maintenance dose 10mg/kg/day.	Other: Control Group; Blinding will be done with the administration of saline solution. Patients in the early caffeine group will receive an attack dose of caffeine 20 mg/kg and begin maintenance dose 10 mg/kg/day. Patients in the late caffeine group, receive bolus of saline solution in the first 2 hours of life, starting, at 24 hours of life, the caffeine-loading dose 20 mg/kg and after maintenance dose 10mg/kg/day. The medical team will prescribe the medication, and the pharmacy will be responsible for randomly dispensing the caffeine or saline solution. The pharmacy will prepare syringes with the medication or saline solution identified by a code referring to the randomization without identifying which solution is being administered. The syringes will be sent to the neonatal ICU and will be administered according to the physician's prescription. The administration will be blinded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Necessity of intubation	Noninvasive ventilation failure will be defined as intubation in the first seven days of life with the need for invasive ventilation for at least 24 hours.	first week of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mechanical ventilation time	Mechanical ventilation time will be counted until first successful extubation (at least 24 hours extubated)	until first successful extubation (followed up at least until 36 weeks of corrected age, discharge or death)
Bronchopulmonary dysplasia	Bronchopulmonary dysplasia will be defined as need for O2 or ventilatory support at 36 weeks corrected gestational age.	followed up at least until 36 weeks of corrected age, discharge or death.
Intracranial hemorrhage	Intracranial hemorrhage will be defined as intracranial hemorrhage grade 3.	followed up at least until 36 weeks of corrected age, discharge or death.
Retinopathy of prematurity	Retinopathy of prematurity will be defined with ROP requiring treatment.	followed up at least until 36 weeks of corrected age, discharge or death.

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2022
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: July 7, 2022
• First Submitted That Met QC Criteria: July 7, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Caffeine
• Other Study ID Numbers: 2021-0463

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No