Target Weaning Oxygen to Determine Cafffeine Duration for AOP (DCAP)

Chongqing Medical University

Status and phase: Completed; Phase 4

Conditions: Caffeine; Medicine Regimen; Apnea of Prematurity; Weaning Oxygen

Treatments: Drug: Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]

Study type: Interventional

Funder types: Other

Identifiers

NCT04868565

20210326

Details and patient eligibility

About

Caffeine, a typical representative of methylxanthine, is world-widely used to manage apnea of prematurity (AOP) in neonatology. However, an appropriate medication regimen of caffeine has not been well defined until now. For example, in terms of the duration of caffeine, AAP guideline for AOP (2016) and British NICE guideline for neonatal respiratory care (2019) all recommended discontinuing caffeine when the infants reached a postmenstrual age (PMA) ≥33weeks and had a stable respiratory status, commonly manifested by weaning from non-invasive ventilation and free of apneic episodes for at least five consecutive days. Interestingly, the actual clinical settings seem to be not strictly following this recommendation. A survey of the neonatologist in North America revealed that a substantial variability existed among sites in the timing of caffeine discontinuation before discharge and the respiratory support at the time of caffeine discontinuation [1]. Another survey in Saudi Arabia also had a similar finding [2]. The optimal timing of discontinuing caffeine is still a conundrum in the field of neonatology.

Ideally, the optimal timing of discontinuing caffeine should be individual-specific. Published work has indicated that AOP and intermittent hypoxemia (IH) were frequently observed beyond 36 weeks' PMA in all gestational age groups, particularly in the 24- to 27-week infants [3, 4]. In the clinical settings, intermittent hypoxic and AOP episodes is a predominant cause of oxygen supplement in premature infants and commonly prolong the hospital stay. Optimizing arterial saturation by oxygen supplement is essential to achieve a stable cardiorespiratory status because hypoxemia could induce hypoxic sensitivity of the carotid bodies in neonates, resulting in more pronounced ventilatory depression and more frequent apneic episodes. Some RCTs have shown that continuing caffeine administration beyond PMA 34 weeks could reduce the frequency of IH episodes in premature infants [4, 5]. Therefore, theoretically, a prolonged caffeine administration over the usual duration could shorten the duration of oxygen supplements in those infants at high risk of frequent late AOP or IH. Target weaning oxygen could be an opportunistic indicator of discontinuing caffeine.

In light of the above considerations, a multicenter, retrospective, partially blinded, controlled trials will be conducted to verify the hypothesis that a novel caffeine regimen that weaning oxygen as the indicator of discontinuing caffeine could improve respiratory outcomes of very premature infants.

Enrollment: 310 patients

Sex: All

Ages: 14 days to 6 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• premature infants with gestational age <30 weeks
• postmenstral age ≥32weeks
• a history of caffeine therapy
• no current positive pressure respiratory support, and free of apnea for at least five consecutive days, but still oxygen dependent
• parents or legal guardians sign informed consent to attend this study

Exclusion criteria

• congenital cardiorespiratory malformation, or chromosomal abnormalities
• Grade III/IV intraventricular hemorrhage, or probable brain injury attributable to confirmed central nervous system infection, severe periventricular leukomalacia or other entities;
• underwent tracheostomy
• currently on sedatives, opioids, or other medication related to depressed breath

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

310 participants in 2 patient groups

ongoing caffeine with oxygen supplement (group 1)

Experimental group

Description:

samples assigned to the "ongoing caffeine with oxygen supplement (group 1)" will continue caffeine administration combining with oxygen supplement until the patients are weaned from oxygen.

Treatment:

Drug: Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]

discontinuing caffeine with oxygen supplement (group 2)

Active Comparator group

Description:

samples assigned to the "discontinuing caffeine with oxygen supplement (group 2)" will discontinue caffeine immediately after randomization, while oxygen supplement is going on.

Treatment:

Drug: Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]