caffeine citrate / Generic mfg. - LARVOL DELTA

Association of caffeine citrate plus vitamin A/D drops with bronchopulmonary dysplasia and respiratory outcomes in preterm infants born at <32 weeks' gestation: a 72-h landmark retrospective cohort study. (PubMed, Front Pediatr) - "Among infants who survived to 72 h, early initiation of vitamin A/D drops as an adjunct to caffeine was associated with lower risks of BPD and death or BPD, as well as more favorable short-term respiratory outcomes. Non-randomized treatment allocation, complete-case selection, and residual confounding preclude causal inference."

Journal • Retrospective data • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Exploring the Suitability of High-Performance Thin-Layer Chromatography for the Analysis of Drug Admixtures in Total Parenteral Nutrition Using Caffeine, Ibuprofen and Midazolam as Model Drugs. (PubMed, Molecules) - "In this study, previously developed and validated HPTLC methods were verified for their suitability to evaluate the concentrations of three commonly used medications in neonatal intensive care units (NICUs), namely caffeine citrate, ibuprofen arginine, and midazolam hydrochloride. These findings were in line with previous studies that concluded compatibility and reported similar RF and LOD/LOQ values (1.95/5.90 ng/band for caffeine, 252.22/764.30 ng/band for ibuprofen and 10.82/32.78 ng/band for midazolam; R2 ≥ 0.99). As no additional sample pre-treatment was required, HPTLC-based compatibility studies of drug-TPN admixtures may simplify the analytical workflow, making them a cost-effective and time-efficient approach to compatibility testing."

Journal • Critical care

Association of caffeine citrate administration with necrotising enterocolitis in infants < 32 weeks' gestation: a retrospective cohort study. (PubMed, BMJ Open) - "While the incidence of NEC (≥stage IIA) in VPIs has not been affected by caffeine citrate, early administration (within 72 hours after birth) was associated with a reduced incidence of surgical NEC. Furthermore, among VPIs who received invasive ventilation at admission and vasopressors, the administration of caffeine citrate was potentially correlated with a decreased occurrence of NEC (≥stage IIA)."

Journal • Retrospective data • Bronchopulmonary Dysplasia • Critical care • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Retinal Disorders • Retinopathy of Prematurity • Septic Shock

COFIE trail: Caffeine Optimization for Oxygen Saturation Index in ELBW Infants (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: University of Rochester | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2028 ➔ Sep 2029 | Trial primary completion date: Sep 2027 ➔ Jul 2028

Enrollment open • Trial completion date • Trial primary completion date

Association Between Caffeine Citrate Initiation Within the First 2 h of Life and Respiratory Outcomes in Very Preterm Infants: A Single-Center Observational Cohort Study. (PubMed, Children (Basel)) - " Caffeine initiation after the first 2 h of life was associated with higher odds of BPD and BPD or death. These findings support further investigation of very early caffeine timing but do not establish a causal effect because of the observational design, modest sample size, and potential residual confounding."

Journal • Observational data • Bronchopulmonary Dysplasia • Critical care • Pulmonary Disease • Respiratory Diseases

Safety of caffeine citrate in neonates with Congenital Heart Disease receiving continuous infusions of alprostadil. (PubMed, Cardiol Young) - "Other arrhythmias during the treatment course were common and similar between each cohort. Utilising caffeine citrate was not associated with a statistically significant increased incidence of tachycardia in neonates with ductal-dependent CHD on alprostadil infusions at the University of Florida."

Journal • Review • Cardiovascular • Heart Failure

Acute kidney injury in early preterm neonates with severe birth asphyxia: Incidence, predictors and role of caffeine initiation timing. (PubMed, J Neonatal Perinatal Med) - "Positive fluid balance at 48 h was an independent predictor. These findings suggest early caffeine initiation as a potentially modifiable factor associated with reduced AKI risk and identify fluid balance as a clinically relevant early marker in this high-risk population."

Journal • Acute Kidney Injury • Critical care • Nephrology • Renal Disease

The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study (clinicaltrials.gov) - P2 | N=250 | Completed | Sponsor: University of Michigan | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Cognitive Disorders

The effect of nasal olfactory stimulation on apnea of prematurity: a randomized cross-over trial. (PubMed, Pediatr Res) - "Clinical trials have demonstrated that olfactory stimulation, using odors such as vanilla, may reduce the frequency of apnea and desaturation episodes in spontaneously breathing preterm infants. This study evaluates the effect of olfactory stimulation with vanilla and strawberry odor on the respiratory drive of preterm infants receiving nasal continuous positive pressure support - the population most severely affected by the apnea of prematurity. In this population, olfactory stimulation did not significantly reduce the number of desaturations and bradycardia. Future research may focus on optimizing delivery methods to ensure that olfactory stimuli are effectively perceived by infants on non-invasive respiratory support."

Journal • Cardiovascular

Personalization of Caffeine Therapy for Apnea of Prematurity: A Potential Role for Sensor Technologies? (PubMed, Sensors (Basel)) - "Apnea of prematurity (AOP) remains a critical challenge in neonatal care, with caffeine citrate serving as the cornerstone of pharmacological intervention...Based on a synthesis of current monitoring literature, we propose a theoretical, comprehensive monitoring system utilizing the area under the respiratory curve (rAUC) as a continuous proxy metric, alongside waveform amplitude analysis aligned with pediatric polysomnography standards...This conceptual model bridges the gap between advanced signal processing and clinical oversight, offering a scalable pathway toward precision dosing. By shifting from reactive to predictive neonatology, sensor-driven optimization can enhance therapeutic efficacy, reduce alarm fatigue, and ultimately improve developmental outcomes for preterm infants."

Journal • Review • Cardiovascular • Critical care • Fatigue • Pediatrics

CHIME: Caffeine for Hypoxic Ischemic Encephalopathy (clinicaltrials.gov) - P3 | N=830 | Recruiting | Sponsor: NICHD Global Network for Women's and Children's Health | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders

Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia (clinicaltrials.gov) - P4 | N=340 | Recruiting | Sponsor: University of Alabama at Birmingham | Not yet recruiting ➔ Recruiting

Enrollment open

Dose Optimization of Caffeine for HIE (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: University of North Carolina, Chapel Hill | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2028 ➔ Jul 2028 | Trial primary completion date: Dec 2026 ➔ Jul 2026

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders

Caffeine treatment for apnea in infants and children: protocol for a systematic review and meta-analysis. (PubMed, Syst Rev) - "We will undertake the first rigorous evidence synthesis examining the safety and efficacy of caffeine treatment for apnea in hospitalized pediatric patients, where studies of premature babies with apnea of prematurity will be specifically excluded. We aim to fill the identified knowledge gap with this systematic review."

Journal • Retrospective data • Critical care • Pediatrics

AnteCaff: Pharmacokinetics and Placental Transfer of Caffeine (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Indiana University | Trial primary completion date: Mar 2027 ➔ Jun 2027 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial primary completion date • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Clinical and biological impact of caffeine therapy in premature infants with apnea of prematurity: a prospective observational study. (PubMed, Front Med (Lausanne)) - "Major complications in caffeine group were intracranial hemorrhage (5.33%) and convulsions followed by death (4.00%) as, while the CoG demonstrated fewer adverse outcomes and more favorable clinical evolution. Intermittent administration of standard methylxanthine doses or adjustment of therapeutic doses, guided by serial monitoring of serum caffeine citrate titer, may improve clinical outcomes in critical cases, reduce adverse drug effects, and support safer and individualized therapeutic management of apnea of prematurity."

Journal • Observational data • Cerebral Hemorrhage • CNS Disorders • Epilepsy • Hematological Disorders

Improving Preterm Kidney Outcomes With Caffeine (clinicaltrials.gov) - P2 | N=114 | Recruiting | Sponsor: University of Wisconsin, Madison | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Nephrology • Renal Disease • Vascular Neurology

Caffeine citrate increases ciliary beat frequency in human respiratory epithelial cells. (PubMed, Mol Cell Pediatr) - "This study reveals a novel pharmacological effect of caffeine citrate-direct stimulation of CBF in primary hRECs through RYR-dependent Ca²⁺ signaling. By improving mucociliary clearance, caffeine citrate may offer peripheral airway benefits in addition to its central actions for apnea prevention. Given its favorable pharmacokinetic profile, long half-life, and good tolerability compared to other methylxanthines, caffeine citrate warrants further evaluation as a dual-action therapy for respiratory diseases with compromised clearance, including CF and bronchopulmonary dysplasia. These findings expand the mechanistic understanding of caffeine's actions and highlight new translational opportunities in respiratory care."

Journal • Bronchopulmonary Dysplasia • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

COST-EFFECTIVENESS AND BUDGET IMPACT OF CAFFEINE CITRATE VERSUS AMINOPHYLLINE FOR APNEA OF PREMATURITY ACROSS A PUBLIC HEALTHCARE SYSTEM IN MEXICO (ISPOR 2026) - "This study evaluates the cost-effectiveness and budget impact of Peyona® (caffeine citrate; CC) compared with aminophylline for the treatment of apnea of prematurity from the perspective of the ISSSTE in Mexico. A cost-effectiveness analysis combined with a budget impact analysis was conducted from the institutional perspective of ISSSTE. CC represents a cost-effective and cost-saving alternative to aminophylline for the management of apnea of prematurity within ISSSTE, supporting efficient resource allocation and long-term economic sustainability of neonatal care programs."

Cost effectiveness • HEOR • Prematurity

AnteCaff: Pharmacokinetics and Placental Transfer of Caffeine (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Indiana University

New P1 trial • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

COFIE trail: Caffeine Optimization for Oxygen Saturation Index in ELBW Infants (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: University of Rochester | Trial completion date: Sep 2027 ➔ Sep 2028 | Initiation date: Mar 2026 ➔ Jun 2026

Trial completion date • Trial initiation date

Association of Caffeine Citrate Administration with Necrotizing Enterocolitis in Infants < 32 Weeks' Gestation: A Retrospective Cohort Study (PAS 2026) - "Compared with VPIs who did not receive caffeine citrate, those who did have lower GA and birth weight, a higher rate of inborn, small for gestational age, antenatal corticosteroid, 1-minute Apgar score ˂ 8, higher TRIPIS score, blood transfusion, and vasopressors usage. Caffeine citrate exposure did not affect the incidence of NEC (≥ stage IIA) between groups; however, its early administration (within 72 hours after birth) was associated with a lower incidence of surgical NEC (adjusted odds ratio [aOR], 0.76; 95% CI, 0.64-0.89). In subgroup analysis, caffeine citrate administration was associated with a reduction incidence of NEC (≥ stage IIA) among VPIs receiving invasive ventilation at admission (aOR, 0.73; 95% CI, 0.58-0.93) and vasopressors (aOR, 0.64; 95% CI, 0.52-0.78).Conclusion(s): While the incidence of NEC (≥ stage IIA) in VPIs has not been affected, early caffeine citrate administration (within 72 hours after birth) was associated with a reduced incidence of..."

Retrospective data • Bronchopulmonary Dysplasia • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Retinal Disorders • Retinopathy of Prematurity • Septic Shock • Small for Gestational Age

Incidence and risk factors of vancomycin-associated nephrotoxicity among neonates in the intensive care unit: a retrospective cohort study. (PubMed, Pediatr Nephrol) - "Lower postmenstrual age independently predicted vancomycin-associated AKI. Lower neonatal weight and AKI were associated with increased mortality, reinforcing the importance of individualized monitoring during vancomycin therapy."

Journal • Retrospective data • Acute Kidney Injury • Critical care • Nephrology • Renal Disease

The Caffeine, Postoperative Delirium, and Change in Outcomes After Surgery (CAPACHINOS-2) Study (clinicaltrials.gov) - P2 | N=250 | Active, not recruiting | Sponsor: University of Michigan | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Cognitive Disorders

Current Status of Caffeine Discontinuation Timing in Preterm Infants ＜32 Weeks Gestational Age: An Analysis from the China Neonatal Network NICUs (PAS 2026) - "Objective: To investigate the current status of caffeine citrate discontinuation timing in preterm infants with a gestational age of < 32 weeks admitted to units of the China Neonatal Network (CHNN) from 2022 to 2023... The median PMA at caffeine discontinuation was 34.1 (IQR 2.1) weeks. The failure rate of caffeine discontinuation progressively declined with increasing gestational age. Significant differences in the PMA at final discontinuation were observed in several subgroups."

Prematurity • Bronchopulmonary Dysplasia • Hypertension • Infectious Disease • Perinatal Disorders • Pulmonary Disease • Respiratory Diseases • Septic Shock • Small for Gestational Age