Caffeine Citrate Use and Electronic Activity of the Diaphragm (EDI) Changes

Changes in Diaphragmatic Activity Before and After Caffeine Citrate Administration and Discontinuation

Caffeine citrate, the first-line agent for apnea of prematurity, enhances diaphragmatic activity. EDI values of neurally adjusted ventilatory assist (NAVA) modes can be used to quantify the diaphragmatic activity triggered by electrical impulse from the respiratory center. This study aims to evaluate the EDI changes following caffeine citrate administration and cessation in preterm infants, and whether such changes are affected by different doses used variably in clinical settings.

Study Overview

• Status: Completed
• Conditions: Apnea of Prematurity; Caffeine; Preterm
• Intervention / Treatment: Drug: caffeine citrate

Detailed Description

Caffeine citrate has been used as the first-line agent for apnea of prematurity. It works via mechanisms including stimulation of the respiratory center in medulla, increasing sensitivity to carbon dioxide retention, and increment in diaphragmatic activity. The effect of caffeine citrate has been evaluated largely based on parameters concerning clinical symptoms (e.g., decrease in the number of apnea, extubation success, decreased incidence of bronchopulmonary dysplasia) but not quantified parameters of actual diaphragmatic activity. Also, while usual doses of caffeine administration is described in the literature, consensus on the effect of caffeine citrate depending on different dosages has not been established.

The current study aims to evaluate effect of caffeine citrate by quantifying the electrical impulses of diaphragmatic activity using EDI values captured from neurally adjusted ventilatory assist (NAVA) mode.

Out of preterm infants necessitating invasive or non-invasive ventilators, those who are supported by invasive or non-invasive NAVA would be recruited. EDI changes would be monitored for the following timepoints: at the administration of caffeine citrate loading dose, 1st maintenance dose after loading, and at cessation of caffeine citrate.

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

• Study Contact: Name: Sook Kyung Yum, MD, PhD; Phone Number: +82-2-2258-6993; Email: cookieyyum@gmail.com
• Study Contact Backup: Name: Yumi Seo, MD; Phone Number: +82-2-2258-6767; Email: nefertaris@naver.com

Study Locations

• Korea, Republic of
  • Seocho-Gu
    • Seoul, Seocho-Gu, Korea, Republic of, 06591
      • Seoul st. mary's hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Preterm infants admitted to the neonatal intensive care unit of the study site

Description

Inclusion Criteria:

• Preterm infants born at less than 34 weeks' gestation who are supported by invasive or non-invasive NAVA

Exclusion Criteria:

• major congenital anomaly, chromosomal or genetic abnormality

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Low-dose group; Infants receiving low dose caffeine citrate (up to 10mg/kg/day)	Drug: caffeine citrate; caffeine citrate administration, dosage decided by the the physician on duty, within the range of routine management (5mg/kg/day ~ 20mg/kg/day); Other Names: caffeine; Neocaf injection [20mg] (Pharmbio Korea Inc.); Neocaf solution [20mg] (Pharmbio Korea Inc.)
High dose group; Infants receiving high dose caffeine citrate (exceeding 10mg/kg/day)	Drug: caffeine citrate; caffeine citrate administration, dosage decided by the the physician on duty, within the range of routine management (5mg/kg/day ~ 20mg/kg/day); Other Names: caffeine; Neocaf injection [20mg] (Pharmbio Korea Inc.); Neocaf solution [20mg] (Pharmbio Korea Inc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EDI change after caffeine citrate loading dose	changes in EDI min and EDI peak values (μV) after the loading dose administration	20 minutes before ~ 20 minutes after loading dose of caffeine citrate
EDI change after caffeine citrate maintenance dose	changes in EDI min and EDI peak values (μV) after the 1st maintenance dose	20 minutes before ~ 20 minutes after 1st maintenance dose of caffeine citrate
EDI change after caffeine citrate cessation	changes in EDI min and EDI peak values (μV) after caffeine discontinuation	20 minutes before ~ 48 hours after caffeine citrate discontinuation (discontinuation time point definition: 48~96 hours after the last dose of caffeine citrate administration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
short-term effect of caffeine citrate administration	number of apnea and/or bradycardia	24 hours before ~ 24 hours after caffeine citrate administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
respiratory outcome of caffeine citrate administration (1)	duration of invasive mechanical ventilation (days)	During neonatal intensive care unit stay up to 48 weeks postmenstrual age (average of 3 months)
respiratory outcome of caffeine citrate administration (2)	bronchopulmonary dysplasia severity (no/mild/moderate/severe)	36 weeks postmenstrual age or at discharge, whichever comes first

Collaborators and Investigators

• Sponsor: Seoul St. Mary's Hospital
• Investigators: Principal Investigator: Sook Kyung Yum, MD, PhD, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2022
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: May 20, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 26, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; 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: KC22OISI0314

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No