Caffeine administration for preterms in nociception outcomes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Masarykova Univerzita

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

18 May 2026 → ongoing

Decision date (initial)

2026-02-09

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Masarykova univerzita · AZV grant

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Pharmacodynamic

The primary objective is to evaluate the salivary caffeine concentrations during the study with respect to the efficacy outcome measured as the cumulative duration of invasive respiratory support (IRS).

Secondary objectives 7

1. 1) Feasibility of using non-invasively collected saliva samples to determine CYP1A2 phenotype with the use of caffeine to paraxanthine salivary concentration ratio
2. 2) Comparison of the pharmacokinetics of caffeine between the two GA subgroups after a standard dose, with particular attention to expected differences in therapy duration.
3. 3) To describe salivary caffeine concentrations with respect to clinical efficacy and safety outcomes overall and in each GA subgroup.
4. 4) Incidence of prematurity-related complications at 36 weeks postmenstrual age (i.e., gestational age plus chronological age).
5. 5) Evaluate the impact of caffeine on pain perception and specifically, the association between salivary caffeine concentrations and pain perception in preterm newborns overall and in GA subgroups to determine whether the magnitude of this effect differs based on exposure duration.
6. 6) Incidence and severity of caffeine adverse reactions in both GA subgroups and the assessment of whether adverse reaction profiles differ based on therapy duration and caffeine metabolism, while considering the causal relationship to typical prematurity-related complications (i.e., PDA, delay in establishing enteral feeds, anemia, irritability, polyuria, slow weight gains).
7. Exploratory Objectives: 1. The selected efficacy endpoints will be analyzed by statistical modeling in relation to caffeine concentration levels measured during treatment. Endpoints of interest will include the duration and type of respiratory support, the occurrence of apneic episodes, pain assessment scores, and vital function parameters. Modeling of these endpoints will be performed only if it is considered statistically meaningful, for example, if the assumed linear association between the endpoint and caffeine concentration is not contradicted during the examination of the primary and secondary objectives. 2. Comparison of CYP1A2 metabolic activity between the two GA subgroups, investigating whether metabolic capacity varies with GA and influences treatment response.

Conditions and MedDRA coding

Primary apnea in preterms newborns

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patients are eligible for the trial if they meet all the following criteria: 1) Gestational age for extreme preterm (24+0 – 27+6 weeks GA) or very early preterm (28+0–32+6 weeks GA) newborn 2) Indication for the treatment with caffeine citrate (Peyona) decided by the attending neonatologist 3) Intravenous access port present of planned to be inserted on Day 0 because of the health status of the patient 4) Medical condition that allows saliva collection using a sterile gauze pad 5) Signed informed consent from one of the parents

Exclusion criteria 1

1. Patients will not be eligible for the trial if they meet any of the following criteria: 1) Caffeine contraindication according to the SmPC 2) Presence of severe congenital malformation or peripartal trauma affecting cerebral blood flow and/or cardiovascular function 3) Serious or life-threatening conditions causing partial or complete loss of sensitivity 4) Post-surgical status (recent major surgical intervention) of the infant or planned major surgery in the next 4 weeks 5) Congenital defect of the urogenital system known to affect renal function

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. a) Exploration 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).

Secondary endpoints 7

1. 1. a) Proportion of preterm newborns in whom the concentrations of caffeine and paraxanthine can be reliably measured from saliva samples.
2. 2. a) Salivary caffeine concentrations over time b) Relationship between caffeine dose and concentration over time.
3. 3. a) Relationship between salivary caffeine concentrations and: • Frequency (Apnea of Prematurity events per 24 hours) and severity of apneic episodes (detail in Section 6.7.3.) • The need for respiratory support, considering its duration and type • Time to successful withdrawal of caffeine therapy
4. 4. a) Incidence of prematurity-related complications: BPD, ROP, PDA, periventricular hemorrhage/intraventricular hemorrhage (PVH/IVH), periventricular leukomalacia (PVL), posthemorrhagic hydrocephalus (PHH), neonatal seizures, and others.
5. 5. a) Evaluation of pain assessment scores (COMFORTneo Scale) and vital function parameters (heart rate, blood pressure) in relation to concentration and exposure duration.
6. 6. a) Comparison of the incidence and severity of adverse events of special interest (AESI) related to caffeine therapy in relation to caffeine concentration levels: • CVS: Tachycardia (for definition see Section 6.7.2) • CNS: Convulsion, brain injury, irritability, jitters, shaking • GIT: Feeding intolerance, necrotizing enterocolitis • Investigations: Urine output increased
7. Exploratory endpoints 2. a) CYP1A2 metabolic activity (caffeine/paraxanthine ratio in saliva) in both GA subgroups and correlation with caffeine therapy duration. b) Evaluation of the analgesic effect of caffeine in relation to CYP1A2 metabolic activity. c) Relationship between CYP1A2 metabolic phenotype and treatment efficacy or caffeine-related adverse events (e.g., tachycardia, feeding intolerance).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Masarykova Univerzita

Sponsor organisation

Masarykova Univerzita

Address

Zerotinovo Namesti 617/9, Brno-Mesto Brno-Mesto

City

Brno-Stred

Postcode

602 00

Country

Czechia

Scientific contact point

Organisation

Masarykova Univerzita

Contact name

Regina Demlová

Public contact point

Organisation

Masarykova Univerzita

Contact name

Regina Demlová

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications