Target Weaning Oxygen to Determine Cafffeine Duration for AOP
Condition: Apnea of Prematurity; Caffeine; Weaning Oxygen; Medicine Regimen
MeSH terms: Apnea; Premature Birth
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    


Intervention name(s): Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]
Intervention type(s): Drug
Intervention description(s): after randomization, caffeine citrate will be contineously prescribed to those patients assigned to the "ongoing caffeine with oxygen supplement (group 2) with a medication regimen of 10mg/kg.dose, once daily, and weekly adjustment based on the working weight.
Intervention MeSH terms: Caffeine; Caffeine citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: apnea of prematurity; caffeine; discontinuation