The primary objective of the study is to characterize safety, efficacy and exposure-response relationship of caffeine citrate. The study included the retrospective analysis of clinical data for premature infants who received caffeine citrate per standard of care (SOC), gathered from three sources. Caffeine citrate used at greater doses for longer durations in more immature (e.g., lower Gestational Age) infants than the FDA label appears to be a safe therapy for the treatment of Apnea of Prematurity. Caffeine citrate use is not associated with an increased risk for Necrotizing Enterocolitis.”

Contents

• 2. Synopsis
• 4. Glossary of Abbreviations and Terms
• 5. Ethics
  • 5.1. Institutional Review Board
  • 5.2. Ethical Conduct of the Study
  • 5.3. Participant Information, Consent, and Assent
• 6. Investigator and Study Administrative Structure
  • 6.1. Principal Investigator
  • 6.2. Administrative Structure
• 7. Introduction
  • 7.1. Caffeine Citrate and Apnea of Prematurity (AOP)
  • 7.2. Data Sources for This Report
  • 7.3. Clinical Study Report (CSR) Structure
• 8. Study Objectives
• 9. Investigational Plan
  • 9.1. Overall Design and Plan
  • 9.2. Selection of Study Population
  • 9.3. Treatments
  • 9.4. Safety and Efficacy Variables
  • 9.5. Data Quality Assurance
  • 9.6. Statistical Methods Planned in the Protocol and Determination of Sample Size
  • 9.7. Dose Response Summaries of Events of Special Interest
  • 9.8. Changes in the Conduct of the Study or the Planned Analyses
  • 9.9. Additions to the Planned Analyses
• 10. Study Participants
  • 10.1. Disposition of Participants
  • 10.2. Protocol Deviations and Waivers
• 11. Efficacy Evaluation
  • 11.1. Data Analyzed
  • 11.2. Summary of CAP Trial Results for Apnea of Prematurity
  • 11.3. Efficacy Conclusions
• 12. Safety Evaluation
  • 12.1. Retrospective Analyses
  • 12.2. CAP Trial Safety Results
  • 12.3. Safety Conclusions
• 13. Discussion and Overall Conclusions
  • 13.1. Discussion
  • 13.2. Conclusions
• 14. Tables, Figures, and Graphs Referred to but not Included in the Text
  • 14.1. Demographic Data (EHR Data)
  • 14.2. Safety Data (EHR Data)
  • 14.3. Dosing Data (EHR Data)
• 15. Reference List
• 16. Appendices

Study data is available on the DASH repository at https://dash.nichd.nih.gov/study/19261

This study was conducted in compliance with Good Clinical Practices (GCP) as outlined by the International Council on Harmonisation (ICH), including the archiving of essential documents. All unpublished information contained within this report is confidential and the sole property of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).