Clinical trial NCT04868565: Target Weaning Oxygen to Determine Cafffeine Duration for AOP
Official title: Target Weaning Oxygen to Determine Duration of Caffeine for Apnea of Prematurity: a Multicenter, Prospective, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Apnea of Prematurity
Caffeine
Weaning Oxygen
Medicine Regimen
Keywords: apnea of prematurity
caffeine
discontinuation
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2021-05-03
Enrollment: 310
Sex: ALL
Minimum age (years): 14
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: recurrence of apnea of prematurity (RAP)
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: duration of oxygen supplement after randomization
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: duration of hospital stay after randomization
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary outcomes:
measure: postmenstrual age of discharging home
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: onset of bronchopulmonary dysplasia
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: severity of bronchopulmonary dysplasia
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: restart caffine therapy
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: restart noninvasive ventilation
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: reintubating the patients
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
measure: hospitalization cost after randomization
timeFrame: from date of randomization until the date of discharge, assessed up to 100 days of life
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC（University of Science and Technology of China）
state: Anhui
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Chongqing
country: China
facility: Yuan Shi
state: Chongqing
city: Chongqing
country: China
facility: First Affiliated Hospital of Army Military Medical University
state: Chongqing
city: Dazu
country: China
facility: The People's Hospital of Dazu
state: Chongqing
city: Fuling
country: China
facility: Fuling Central Hospital of Chongqing City
state: Chongqing
city: Wanzhou
country: China
facility: Chongqing University Three Gorges Hospital
state: Chongqing
city: Wanzhou
country: China
facility: Chongqing Wanzhou Health Center for Women And Children
state: Chongqing
city: Fuzhou
country: China
facility: Fuzhou Children's Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: Xiamen Children's Hospital
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Dongguan
country: China
facility: Dongguan City Maternal&Child Health Hospital
state: Guangdong
city: Yunfu
country: China
facility: Maternal and Child Health Hospital of Yunfu
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital Of Guangdong Medical University
state: Guangdong
city: Zhongshan
country: China
facility: BOAI hospital of Zhongshan
state: Guangdong
city: Haikou
country: China
facility: Haikou Hospital of the Maternal and Child Health
state: Hainan
city: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: The Third Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
city: Hengyang
country: China
facility: Hengyang Maternity and Child care hospital
state: Hunan
city: Nanjing
country: China
facility: Children's Hospital of Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: First Affiliation Hospital of Nanjing Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The first bethune hospital of Jilin university
state: Jilin
city: Jinan
country: China
facility: Qilu Children's Hospital of ShanDong University
state: Shandong
city: Linyi
country: China
facility: Women & Children's Health Care Hospital of Linyi
state: Shandong
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
state: Shanghai
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Guangyuan
country: China
facility: Guangyuan central hospital
state: Sichuan
city: Leshan
country: China
facility: People's Hospital Of Leshan
state: Sichuan
city: Luzhou
country: China
facility: Hospital T. C. M Affiliated to Southwest Medical University
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Panzhihua
country: China
facility: Panzhihua Central Hospital
state: Sichuan
city: Yibin
country: China
facility: The Second People's Hospital of Yibin
state: Sichuan
city: Kunming
country: China
facility: Kunming Children's Hospital
state: Yunnan
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Qujing
country: China
facility: Qujing City Maternal and Child Health Hospital
state: Yunnan
city: Wenshan
country: China
facility: The People's Hosiptal of Wenshan Prefecture
state: Yunnan
city: Zhaotong
country: China
facility: The First People's Hospital of Zhaotong
state: Yunnan
city: Ningbo
country: China
facility: Ningbo Women & Children's Hospital
state: Zhejiang
Study officials:
affiliation: Children's Hospital of Chongqing Medical University
name: Yuan Shi
role: STUDY_DIRECTOR
References: