Caffeine as Respiratory Stimulant in Preterm Infants

High Versus Low Dose Caffeine as Respiratory Stimulant in Preterm Infants

comparison between rate of occurance of apnea of prematurity AOP when using high and low dose caffeine

Study Overview

• Status: Unknown
• Conditions: Apnea of Prematurity
• Intervention / Treatment: Drug: Caffeine Citrate

Detailed Description

Caffeine is one of the widely used medications in the neonatal care units and in spite of its widespread use in preterm infants, there has been little information about the optimal efficient dose in those patients Caffeine therapy for treatment of apnea of prematurity (AOP) is well established over the past few years, yet the optimal loading and maintenance dose of caffeine in preterm infants is not well-studied AOP is a common complication of preterm birth, which affects more than 80 % of neonates with a birth weight less than 1,000 g. Methylxanthine (MGs), including caffeine and theophylline, are a mainstay in the treatment and prevention of AOP The efficiency of caffeine, as a preferred methylxanthine, to stimulate respiration has been well proven as it has a significant favorable impact on neonatal morbidity as bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) ligation. Also, the results of previous studies revealed that caffeine enhances respiratory muscle strength and lung function followed by easier weaning of mechanical ventilation in premature infants. Besides, a rapid and sustained increase in diaphragmatic activity and tidal volume was reported in preterm infants followed by caffeine administration Previous studies have shown that caffeine citrate was generally well tolerated by premature neonates in clinical trials and declined the incidence of apnea in this population compared with placebo. Also, caffeine is related to superior outcomes due to its lower toxicity and it is a preferred drug for apnea in preterm infants with respiratory problems. It has also a significant function as a noninvasive respiratory support. It facilitates the transition from invasive to noninvasive support, reduces the duration of positive airway pressure support and decreases the risk of BPD in preterm infants The optimum caffeine dose in preterm infants with AOP has not been well studied as well as heterogeneous reports on the optimal loading and maintenance dose of caffeine in several studies in terms of benefits and risks. Many investigations have been conducted about various dosing regimens in the improvement or prevention of respiratory disorders of premature infants. These dosage regimens, although, have been associated with varying degrees of success The aim of this study is to determine if the use of caffeine in doses higher than the currently standard dose can decrease the frequency of apnea in preterm infants without causing significant side effects

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11591
    • Recruiting
    • Faculty of Medicine Ain Shams University
    • Contact: Yasmin A Farid, MD; Phone Number: 20101001449558; Email: yasmin_aly_farid@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Preterm infants with a gestational age <32 weeks in room air or CPAP (prophylactic).

  • Preterm infants with gestational age 32-34 weeks who exhibited apnea of prematurity within the first 10 days of life in room air or CPAP

Exclusion Criteria:

• • Major congenital malformations.

  • Chromosomal anomalies.
  • Preterm infants on mechanical ventilation.
  • Preterm infants on NIPPV.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Dose arm; subjects will receive the high dose of the drug	Drug: Caffeine Citrate; study rate of occurrence of Apnea of Prematurity between the 2 groups
Active Comparator: low dose arm; subject will receive low dose of the drug	Drug: Caffeine Citrate; study rate of occurrence of Apnea of Prematurity between the 2 groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High Versus Low Dose Caffeine as Respiratory Stimulant in Preterm Infants	assess occurrence of apnea of prematurity between infants receiving high and low dose caffeine	baseline

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Director: Yasmin A Farid, MD, Pediatric Department Faculty of Medicine Ain shams University; Study Chair: Ola G Badr El-Deen, MD, Pediatric Department Faculty of Medicine Ain shams University

Publications and helpful links

General Publications

• Faramarzi F, Shiran M, Rafati M, Farhadi R, Salehifar E, Nakhshab M. The efficacy and safety of two different doses of caffeine in respiratory function of preterm infants. Caspian J Intern Med. 2018 Winter;9(1):46-53. doi: 10.22088/cjim.9.1.46.
• Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
• Kraaijenga JV, Hutten GJ, de Jongh FH, van Kaam AH. The Effect of Caffeine on Diaphragmatic Activity and Tidal Volume in Preterm Infants. J Pediatr. 2015 Jul;167(1):70-5. doi: 10.1016/j.jpeds.2015.04.040. Epub 2015 May 15.
• Mohammed S, Nour I, Shabaan AE, Shouman B, Abdel-Hady H, Nasef N. High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial. Eur J Pediatr. 2015 Jul;174(7):949-56. doi: 10.1007/s00431-015-2494-8. Epub 2015 Feb 3.
• Zhao Y, Tian X, Liu G. [Clinical effectiveness of different doses of caffeine for primary apnea in preterm infants]. Zhonghua Er Ke Za Zhi. 2016 Jan;54(1):33-6. doi: 10.3760/cma.j.issn.0578-1310.2016.01.008. Chinese.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: October 29, 2019
• First Posted (Actual): October 30, 2019

Study Record Updates

• Last Update Posted (Actual): February 7, 2020
• Last Update Submitted That Met QC Criteria: February 6, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; 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; Caffeine citrate
• Other Study ID Numbers: FWA 000017685

Drug and device information, study documents

• 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