Caffeine citrate for Apnea of prematurity

Inclusion criteria

• {"criterion_text":"- 1)\tGestational age for extreme preterm (24+0 – 27+6 weeks GA) or very early preterm (28+0–32+6 weeks GA) newborn"}
• {"criterion_text":"- 2)\tIndication for the treatment with caffeine citrate (Peyona) decided by the attending neonatologist"}
• {"criterion_text":"- 3)\tIntravenous access port present of planned to be inserted on Day 0 because of the health status of the patient"}
• {"criterion_text":"- 4)\tMedical condition that allows saliva collection using a sterile gauze pad"}
• {"criterion_text":"- 5)\tSigned informed consent from one of the parents"}

Exclusion criteria

• {"criterion_text":"- 1)\tCaffeine contraindication according to the SmPC"}
• {"criterion_text":"- 2)\tPresence of severe congenital malformation or peripartal trauma affecting cerebral blood flow and/or cardiovascular function"}
• {"criterion_text":"- 3)\tSerious or life-threatening conditions causing partial or complete loss of sensitivity"}
• {"criterion_text":"- 4)\tPost-surgical status (recent major surgical intervention) of the infant or planned major surgery in the next 4 weeks"}
• {"criterion_text":"- 5) Congenital defect of the urogenital system known to affect renal function"}

Primary endpoints

• {"endpoint_text":"- a)\tExploration of observed caffeine concentration levels in groups of preterm newborns receiving caffeine therapy, stratified by treatment response as defined by the duration of IRS evaluated on Day 11 and at 36 weeks of postmenstrual age (PMA).","definition_or_measurement_approach":"Salivary caffeine concentrations measured during the study; treatment response defined by duration of invasive respiratory support (IRS) evaluated on Day 11 and at 36 weeks postmenstrual age."}

Secondary endpoints

• {"endpoint_text":"- 1. a)\tProportion of preterm newborns in whom the concentrations of caffeine and paraxanthine can be reliably measured from saliva samples.","definition_or_measurement_approach":"Measurement of caffeine and paraxanthine concentrations from saliva samples; proportion of subjects with reliable assay results."}
• {"endpoint_text":"- 2. a)\tSalivary caffeine concentrations over time b)\tRelationship between caffeine dose and concentration over time.","definition_or_measurement_approach":"Serial salivary concentration measurements and analysis of dose-concentration relationship over time."}
• {"endpoint_text":"- 3. a)\tRelationship between salivary caffeine concentrations and: •\tFrequency (Apnea of Prematurity events per 24 hours) and severity of apneic episodes (detail in Section 6.7.3.) •\tThe need for respiratory support, considering its duration and type •\tTime to successful withdrawal of caffeine therapy","definition_or_measurement_approach":"Correlation analyses between salivary caffeine concentrations and apnea event frequency/severity, respiratory support needs (type and duration), and time to withdrawal of therapy."}
• {"endpoint_text":"- 4. a)\tIncidence of prematurity-related complications: BPD, ROP, PDA, periventricular hemorrhage/intraventricular hemorrhage (PVH/IVH), periventricular leukomalacia (PVL), posthemorrhagic hydrocephalus (PHH), neonatal seizures, and others.","definition_or_measurement_approach":"Recording and incidence calculation of listed prematurity-related complications at specified time points (including 36 weeks PMA)."}
• {"endpoint_text":"- 5. a)\tEvaluation of pain assessment scores (COMFORTneo Scale) and vital function parameters (heart rate, blood pressure) in relation to concentration and exposure duration.","definition_or_measurement_approach":"Assessment of COMFORTneo scores and vital parameters correlated with salivary caffeine concentrations and exposure duration."}
• {"endpoint_text":"- 6. a)\tComparison of the incidence and severity of adverse events of special interest (AESI) related to caffeine therapy in relation to caffeine concentration levels: •\tCVS: Tachycardia (for definition see Section 6.7.2) •\tCNS: Convulsion, brain injury, irritability, jitters, shaking •\tGIT: Feeding intolerance, necrotizing enterocolitis •\tInvestigations: Urine output increased","definition_or_measurement_approach":"Assessment and comparison of AESI incidence/severity stratified by measured caffeine concentration levels."}
• {"endpoint_text":"- Exploratory endpoints 2. a)\tCYP1A2 metabolic activity (caffeine/paraxanthine ratio in saliva) in both GA subgroups and correlation with caffeine therapy duration. b)\tEvaluation of the analgesic effect of caffeine in relation to CYP1A2 metabolic activity. c)\tRelationship between CYP1A2 metabolic phenotype and treatment efficacy or caffeine-related adverse events (e.g., tachycardia, feeding intolerance).","definition_or_measurement_approach":"Measurement of CYP1A2 metabolic activity via caffeine/paraxanthine saliva ratio and correlation analyses with therapy duration, analgesic effect, efficacy and adverse events."}

Other endpoints

• {"endpoint_text":"- Exploratory endpoints 2. a)\tCYP1A2 metabolic activity (caffeine/paraxanthine ratio in saliva) in both GA subgroups and correlation with caffeine therapy duration. b)\tEvaluation of the analgesic effect of caffeine in relation to CYP1A2 metabolic activity. c)\tRelationship between CYP1A2 metabolic phenotype and treatment efficacy or caffeine-related adverse events (e.g., tachycardia, feeding intolerance).","definition_or_measurement_approach":"CYP1A2 metabolic activity assessed by caffeine/paraxanthine ratio in saliva; analyses of correlations with duration of therapy, analgesic endpoints, efficacy and safety outcomes."}

Czechia

Earliest CTIS Part Ii Submission Date

11-11-2025

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

162

Number Of Sites

2

Number Of Participants

200

Primary sponsor

Full Name

Masarykova Univerzita

Organisation Type

Educational Institution

Country Of Registered Address

Czechia