Evaluation of Pre-Extubation Loading Dose of Caffeine Citrate on Extubation Success in Patients with Extubation Failure and Bronchopulmonary Dysplasia

The primary objective of this study is to evaluate whether an additional pre-extubational loading dose of **caffeine citrate** affects the extubation success rate in patients experiencing extubation failure and bronchopulmonary dysplasia. This is clinically relevant as improving extubation success can reduce the need for re-intubation and associated complications, thereby enhancing patient outcomes.

Secondary objectives include assessing the frequency and severity of side effects associated with the treatment. Additionally, the study aims to investigate the impact of caffeine citrate on the development of bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL), as well as the progression of IVH. These objectives are crucial for understanding the broader implications of caffeine citrate use in neonatal care and its potential to mitigate adverse neurological outcomes.

The clinical trial focused on **extubation failure and bronchopulmonary dysplasia** involves a study population of preterm neonates born before the 32nd week of gestation who have been mechanically ventilated for at least 48 hours prior to the first planned extubation. The trial includes both male and female subjects, and the population is considered vulnerable due to the age and health status of the participants. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the inclusion of neonates who meet the specified gestational and ventilation requirements, ensuring a targeted investigation into the effects of an additional pre-extubational loading dose of caffeine-citrate on extubation success rates.

The clinical trial is designed to evaluate the impact of an additional pre-extubational loading dose of **caffeine citrate** on the success rate of extubation in preterm neonates. This study is a **randomized**, **double-blind**, and **controlled** trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is categorized as a Phase IV clinical trial, focusing on the safety and efficacy of the intervention in a real-world setting. The trial is expected to commence recruitment on December 14, 2023, and conclude by April 4, 2027.

Participants will be preterm neonates born before the 32nd week of gestation who have been mechanically ventilated for at least 48 hours prior to the first planned extubation. The primary endpoint of the study is the rate of reintubation, while secondary endpoints include the frequency of apneas, side effects such as elevated heart rate and blood pressure, gastric residuals, necrotizing enterocolitis, bronchopulmonary dysplasia, and neurodevelopmental outcomes. The study will involve multiple visits, starting with a screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits will be scheduled to monitor the participants' response to the treatment and assess any adverse effects. The end-of-study visit will evaluate the overall outcomes and gather final data on the endpoints.

The expected duration of participant involvement is up to six weeks, corresponding to the maximum treatment period with **caffeine citrate**. Participants may be withdrawn from the study if they experience significant adverse effects or if they no longer meet the study criteria. The study will utilize **caffeine citrate** administered via IV injection or infusion, with a maximum daily dose of 40 mg/kg. The trial aims to provide valuable insights into the potential benefits of an additional loading dose of **caffeine citrate** in improving extubation outcomes in this vulnerable population.

The clinical trial involves the administration of **caffeine citrate** as the experimental medication. **Caffeine citrate** is provided in the form of a **solution for injection**. The active substance, **caffeine citrate**, is of chemical origin and is utilized as a **respiratory stimulant**. The medication is administered via **intravenous injection** or **intravenous infusion**. The dosing regimen includes a maximum daily dose of 40 mg/kg, with the same limit for the total dose. The treatment period is capped at a maximum of 6 days. The trial aims to assess the impact of an additional pre-extubational loading dose of **caffeine citrate** on the success rate of extubation.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus remains solely on the administration of **caffeine citrate**. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial does not involve any pediatric formulations, and the product is not classified as an orphan drug. The study is designed to evaluate the efficacy of the additional loading dose in improving respiratory outcomes in the specified clinical context.

Efficacy in this clinical trial will be assessed by evaluating the impact of an additional pre-extubational loading dose of **caffeine citrate** on the extubation success rate in preterm neonates. The primary endpoint for efficacy evaluation is the rate of reintubation. Secondary endpoints include the frequency of apneas, side effects such as elevated heart rate, elevated blood pressure, and gastric residuals, as well as the occurrence of necrotizing enterocolitis, bronchopulmonary dysplasia, and the progression or development of intraventricular hemorrhage or periventricular leukomalacia. Additionally, neurodevelopmental outcomes will be assessed.