caffeine citrate / Generic mfg. - LARVOL DELTA

CAffeine Use in Prolonged Oxygen Use in meConium aspIration Syndrome in Neonatal Outcomes (CAPUCINO) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: University of Alberta | Trial completion date: Dec 2027 ➔ Dec 2028 | Initiation date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Trial initiation date • Trial primary completion date

Association Between Serum Caffeine Concentrations, Intermittent Hypoxia and Apnea in Preterm Infants: A Prospective Observational Study. (PubMed, Children (Basel)) - "While serum caffeine concentrations in preterm infants did not vary significantly with gestational age, lower levels were associated with a higher incidence of AOP and IH episodes. These results suggest that while routine monitoring or dose adjustment based solely on gestational age may not be warranted, maintaining adequate serum levels is critical for symptom management. Future research should prioritize randomized controlled trials with expanded sample sizes, extended follow-up periods, and a rigorous analysis of adverse effects."

Journal • Observational data

COFIE trail: Caffeine Optimization for Oxygen Saturation Index in ELBW Infants (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: University of Rochester | Initiation date: Nov 2025 ➔ Mar 2026

Trial initiation date

Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia (clinicaltrials.gov) - P4 | N=340 | Not yet recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Dec 2026 ➔ Jun 2027 | Trial primary completion date: Dec 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date

The utility of caffeine citrate as a neuroprotectant in the early life of premature newborns: a literature review of the effects on neurodevelopmental outcomes. (PubMed, Front Pediatr) - "Research has shown that caffeine citrate exerts an anti-inflammatory effect via the antagonism of adenosine receptors, reduces the production of reactive oxygen species, and supports the plasticity of the central nervous system. This article aims to review the most up-to-date evidence on caffeine citrate's effects on neuroprotection and its role in reducing the severity of neurodevelopmental impairment associated with prematurity."

Journal • Review • Bronchopulmonary Dysplasia • Critical care • Pulmonary Disease • Respiratory Diseases

Stability of a 20 mg/mL Caffeine Citrate Oral Solution Compounded in a Novel Suspension Vehicle Designed for Pediatric Use (ASHP 2025) - No abstract available

Clinical • Pediatrics

Methylxanthines: The Major Impact of Caffeine in Clinical Practice in Patients Diagnosed with Apnea of Prematurity. (PubMed, J Clin Med) - "Methylxanthines, including caffeine, theophylline, and aminophylline, have emerged as the primary pharmacological intervention for this condition...No external funding was received for this review. No registration record exists for this systematic review."

Journal • Review • Bronchopulmonary Dysplasia • Critical care • Pulmonary Disease • Respiratory Diseases

Stability of caffeine citrate intravenous dilutions in sodium chloride and glucose solutions. (PubMed, Eur J Hosp Pharm) - "Caffeine citrate diluted in 0.9% w/v sodium chloride or 5% w/v glucose is chemically stable at concentrations of 1 mg/mL and 12.5 mg/mL for up to 48 hours when stored at room temperature, meeting ICH and USP acceptance criteria in all cases. Caffeine citrate solutions did not meet the USP±10% criterion if stored at 8°C for 24 hours."

Journal • Critical care

Improving Preterm Kidney Outcomes With Caffeine (clinicaltrials.gov) - P2 | N=102 | Not yet recruiting | Sponsor: University of Wisconsin, Madison

New P2 trial • CNS Disorders • Nephrology • Renal Disease • Vascular Neurology

Physiologically Based Pharmacokinetic Modeling of Caffeine in Preterm Neonates: Influence of Renal Function and Impairment on Dosing. (PubMed, J Clin Pharmacol) - "Currently, the same weight-based caffeine citrate dosing regimen is applied to all neonates...Neonates with significantly reduced renal function (25% of normal) may need a two- to threefold dose reduction. Future studies should aim to define optimal therapeutic targets, as caffeine use continues to expand."

Journal • PK/PD data • Renal Disease • CYP1A2

CAffeine Use in Prolonged Oxygen Use in meConium aspIration Syndrome in Neonatal Outcomes (CAPUCINO) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: University of Alberta | Initiation date: Sep 2025 ➔ Dec 2025

Trial initiation date

Efficacy and safety of intravenously applied caffeine augmentation in electroconvulsive therapy. (PubMed, Neurosci Appl) - "This retrospective study assessed the effects of intravenous caffeine citrate (200 mg) on seizure quality during ECT...Type of anesthesia did not affect outcomes, except for energy set where we observed a significant interaction-etomidate combined with caffeine resulted in a smaller energy increase compared to propofol (F (198) = 0.04, η 2  = 0.04). Our findings suggest that intravenous caffeine augmentation safely enhances seizure length and slows energy set increases in ECT without affecting cardiovascular markers, supporting its use as an effective augmentation strategy to improve ECT efficacy."

Journal • Anesthesia • Bipolar Disorder • Cardiovascular • CNS Disorders • Depression • Epilepsy • Mood Disorders • Psychiatry • Schizophrenia

Caffeine Citrate does not reduce brain injury following inflammation-amplified hypoxia ischaemia or hypoxia ischaemia in the Newborn Piglet Model. (PubMed, Neuropharmacology) - "However, there was a modest benefit in male caffeine-treated piglets following HI. The lack of neuroprotection observed following caffeine citrate treatment after both IA-HI and HI suggests further preclinical studies are required before clinical translation for term babies with NE."

Journal • CNS Disorders • Epilepsy • Inflammation • Vascular Neurology

Oral doxapram for apnea of prematurity: A randomized dosage trial. (PubMed, J Perinatol) - P2 | "Oral doxapram is feasible in very preterm infants with improvements in oxygenation and ventilation. Lower doses (12 mg/kg/6 h) are sufficient in most infants."

Journal

Caffeine-Associated Reduction in Patent Ductus Arteriosus (PDA) is Mediated in Part by Adenosine Receptor Antagonism. (PubMed, Am J Physiol Heart Circ Physiol) - "Pressure myography was used to examine responses of the isolated ductus to adenosine, caffeine (citrate or base), or pre-incubation with either caffeine or adenosine...In conclusion, caffeine did not induce direct ductus constriction ex vivo. However, caffeine exposure prevented adenosine-induced ductus relaxation, suggesting inhibition of an endogenous vasodilator as a mechanism for reduction in PDA."

Journal

COFIE trail: Caffeine Optimization for Oxygen Saturation Index in ELBW Infants (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: University of Rochester

New P2 trial

Caffeine Therapy Reduces Severe Retinopathy of Prematurity in Neonates with Gestational Age between 23 and 28 Weeks. (PubMed, Ophthalmol Sci) - "To investigate the association of caffeine citrate therapy with the onset and exacerbation of retinopathy of prematurity (ROP)...Caffeine therapy may be a potential treatment strategy to prevent the progression of severe ROP in neonates born between 23 and 28 weeks' gestational age. The authors have no proprietary or commercial interest in any materials discussed in this article."

Journal • Acute Respiratory Distress Syndrome • Diabetes • Gestational Diabetes • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Retinal Disorders • Retinopathy of Prematurity

Caffeine to improve neurodevelopmental outcomes in infants born late preterm (The Latte Trial): study protocol for a randomised controlled trial. (PubMed, Trials) - P | "Of early developmental domains, cognition is the most predictive of later neurodevelopmental outcome and intelligence quotient. Prioritisation of the Indigenous population within trials is important. If prophylactic caffeine citrate is found to improve neurodevelopment in late preterm infants, this could have a significant impact on the long-term quality of life and health and wellbeing of this large population of infants."

Journal • Alzheimer's Disease • Cerebral Palsy • CNS Disorders • Cognitive Disorders

Recurrence of apnea of prematurity following early discontinuation of caffeine: A prospective analytical study. (PubMed, J Neonatal Perinatal Med) - "Injection Caffeine citrate was started for all within 2 hours of birth and it was stopped after an apnea-free period of 7 days.ResultsOut of the total 300 neonates enrolled, 285 were available for primary outcome analysis...For judicious use of caffeine, considering its cost and side effects, it may be reasonable to stop it after an apnea-free period of 7 days. Close monitoring is required for 7-10 days in babies less than 1250 g."

Journal • Infectious Disease • Septic Shock

Association of caffeine with renal and other short-term outcomes in neonates with hypoxic-ischaemic encephalopathy undergoing therapeutic hypothermia. (PubMed, BMJ Paediatr Open) - "Caffeine during TH lowered serum creatinine and BUN but did not significantly reduce AKI and was associated with higher rates of MRI lesions. Prospective, dose-controlled trials with pharmacokinetic monitoring and long-term neurodevelopmental follow-up are needed to clarify caffeine's renal benefits and neurological safety in neonatal HIE."

Journal • Retrospective data • Acute Kidney Injury • CNS Disorders • Epilepsy • Nephrology • Renal Disease

To Determine the Effect of KP-001 on Rosuvastatin, Caffeine PK and the Effect of Fluvoxamine on KP-001 PK in Volunteers (clinicaltrials.gov) - P1 | N=38 | Completed | Sponsor: Kaken Pharmaceutical | Recruiting ➔ Completed

Trial completion

Management of apnoea in extremely preterm infants - a European Survey. (PubMed, Neonatology) - "All NICUs reported using caffeine citrate, with 102 centres (23%) starting it in the delivery room (DR). Despite consistency in the dosing and weaning of caffeine, there is much variation in the management of apnoea in preterm infants across Europe. Future research should focus on timing and dosage of caffeine, the use of doxapram, and strategies for optimising non-invasive respiratory support."

Journal • Critical care

Caffeine Citrate in Preterm Infants at Risk of Apnea in Zambia (clinicaltrials.gov) - P4 | N=340 | Not yet recruiting | Sponsor: University of Alabama at Birmingham | Trial primary completion date: Aug 2026 ➔ Dec 2026

Trial primary completion date

Impact of cessation of caffeine citrate therapy on intermittent hypoxemia patterns among preterm infants born before 34 weeks. (PubMed, Front Pediatr) - "Caffeine citrate therapy use beyond 34 weeks is likely to be beneficial especially in the context of LMIC where antenatal steroid is not always administered, and monitoring of preterm babies is suboptimal. Safe cessation of caffeine therapy requires monitoring to detect IH events."

Journal

Caffeine and preterm infants: multiorgan effects and therapeutic creep: scope to optimise dose and timing. (PubMed, Pediatr Res) - "Caffeine has multiorgan effects involving renal, respiratory, and inflammatory responses, which, by optimising dosing and timing, may improve outcomes. Optimising indications, dose, and timing of caffeine citrate in preterm infants in further large-scale trials is warranted and may have other multiorgan benefits."

Journal • Review • Inflammation