Target Weaning Oxygen to Determine Cafffeine Duration for AOP

Target Weaning Oxygen to Determine Duration of Caffeine for Apnea of Prematurity: a Multicenter, Prospective, Randomized Controlled Trial

Sponsors

Lead Sponsor: Children's Hospital of Chongqing Medical University

Source Children's Hospital of Chongqing Medical University
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.

Overall Status Recruiting
Start Date 2021-05-01
Completion Date 2022-04-30
Primary Completion Date 2022-03-31
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
recurrence of apnea of prematurity (RAP) from date of randomization until the date of discharge, assessed up to 100 days of life
duration of oxygen supplement after randomization from date of randomization until the date of discharge, assessed up to 100 days of life
duration of hospital stay after randomization from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary Outcome
Measure Time Frame
postmenstrual age of discharging home from date of randomization until the date of discharge, assessed up to 100 days of life
onset of bronchopulmonary dysplasia from date of randomization until the date of discharge, assessed up to 100 days of life
severity of bronchopulmonary dysplasia from date of randomization until the date of discharge, assessed up to 100 days of life
restart caffine therapy from date of randomization until the date of discharge, assessed up to 100 days of life
restart noninvasive ventilation from date of randomization until the date of discharge, assessed up to 100 days of life
reintubating the patients from date of randomization until the date of discharge, assessed up to 100 days of life
hospitalization cost after randomization from date of randomization until the date of discharge, assessed up to 100 days of life
Enrollment 1064
Condition
Intervention

Intervention Type: Drug

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

Description: 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.

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

Gender:

All

Minimum Age:

N/A

Maximum Age:

6 Months

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Yuan Shi Study Director Children's Hospital of Chongqing Medical University
Overall Contact

Last Name: Jianhui Wang

Phone: +86-13678428167

Email: [email protected]

Location
Facility: Status: Contact:
The First Affiliated Hospital of USTC(University of Science and Technology of China) | Hefei, Anhui, China Recruiting Mingwu Chen +8615215699151
Peking Union Medical College Hospital | Beijing, Beijing, China Not yet recruiting Zhenghong Li +8618501309801
Yuan Shi | Chongqing, Chongqing, 400014, China Recruiting Yuan Shi +86-(023) 63635567 [email protected]
First Affiliated Hospital of Army Military Medical University | Chongqing, Chongqing, China Not yet recruiting Wei Liao +8613896043391
The People's Hospital of Dazu | Dazu, Chongqing, China Not yet recruiting Wenliang Jiang +8613368205892
Fuling Central Hospital of Chongqing City | Fuling, Chongqing, China Recruiting Xiaohua Jiang +8618996889191
Chongqing University Three Gorges Hospital | Wanzhou, Chongqing, China Not yet recruiting Ming Yi +8615178969566
Chongqing Wanzhou Health Center for Women And Children | Wanzhou, Chongqing, China Not yet recruiting Lin Deng +8613668453181
Fuzhou Children's Hospital of Fujian Medical University | Fuzhou, Fujian, China Recruiting Liyan Zhang +8613950418319
Xiamen Children's Hospital | Xiamen, Fujian, China Not yet recruiting Ying Huang +8615959269389
Lanzhou University Second Hospital | Lanzhou, Gansu, China Not yet recruiting Fan Wang +8613609360968
Dongguan City Maternal&Child Health Hospital | Dongguan, Guangdong, China Not yet recruiting Yong Yang +8613316680606
Maternal and Child Health Hospital of Yunfu | Yunfu, Guangdong, China Not yet recruiting Jin'e Li +8613927193812
Affiliated Hospital Of Guangdong Medical University | Zhanjiang, Guangdong, China Not yet recruiting Dang Ao +8613671486782
Haikou Hospital of the Maternal and Child Health | Haikou, Hainan, China Recruiting Yanping Jia +8613976608556
The Second Affiliated Hospital of Zhengzhou University | Zhengzhou, Henan, China Recruiting Hong Song +8613598003821
The Third Affiliated Hospital of Zhengzhou University | Zhengzhou, Henan, China Not yet recruiting Falin Xu +8613663813928
Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan, Hubei, China Recruiting Lingkong Zeng +8613007125718
Hunan Children's Hospital | Changsha, Hunan, China Not yet recruiting Xirong Gao +8613873118991
Hengyang Maternity and Child care hospital | Hengyang, Hunan, China Recruiting Feiyan Xie +8619974727158
Children's Hospital of Nanjing Medical University | Nanjing, Jiangsu, China Not yet recruiting Rui Cheng +8618951769507
First Affiliation Hospital of Nanjing Medical University | Nanjing, Jiangsu, China Not yet recruiting Xiaoqing Chen +8613951676702
The First Affiliated Hospital of Nanchang University | Nanchang, Jiangxi, China Not yet recruiting Xiao Chen +8613970858156
The first bethune hospital of Jilin university | Changchun, Jilin, China Not yet recruiting Hui Wu +8615843079689
Qilu Children's Hospital of ShanDong University | Jinan, Shandong, China Not yet recruiting Xiaoying Li +8615615611398
Women & Children's Health Care Hospital of Linyi | Linyi, Shandong, China Not yet recruiting Qiongyu Liu +8613954982562
Shanghai Children's Medical Center | Shanghai, Shanghai, China Not yet recruiting Fei Bei +8618930830712
The First Affiliated Hospital of Xi'an Jiaotong University | Xi'an, Shanxi, China Not yet recruiting Xihui Zhou +8613700298972
Guangyuan central hospital | Guangyuan, Sichuan, China Recruiting Zhiyong Zhao 13084373070
People's Hospital Of Leshan | Leshan, Sichuan, China Not yet recruiting Li Wang +8613881361595
Hospital T. C. M Affiliated to Southwest Medical University | Luzhou, Sichuan, China Not yet recruiting Xiaoxiu Ye +8618090861576
Mianyang Central Hospital | Mianyang, Sichuan, China Not yet recruiting Jia Chen +8613699626669
Panzhihua Central Hospital | Panzhihua, Sichuan, China Recruiting Dehua Jin +8618096307778
The Second People's Hospital of Yibin | Yibin, Sichuan, China Recruiting Qiang Cai +8613608292789
Kunming Children's Hospital | Kunming, Yunnan, China Not yet recruiting Kun Du +8613888127205
The Second Affiliated Hospital of Kunming Medical University | Kunming, Yunnan, China Not yet recruiting Lin Zhao +8613888410901
Qujing City Maternal and Child Health Hospital | Qujing, Yunnan, China Not yet recruiting Chuanfeng Li +8613988970311
The People's Hosiptal of Wenshan Prefecture | Wenshan, Yunnan, China Not yet recruiting Weihong Yu +8618908761622
The First People's Hospital of Zhaotong | Zhaotong, Yunnan, China Recruiting Hanmei Xiong +8613508709995
Ningbo Women & Children's Hospital | Ningbo, Zhejiang, China Recruiting Qin Lü +8613989370791
Location Countries

China

Verification Date

2021-08-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Children's Hospital of Chongqing Medical University

Investigator Full Name: Wang Jianhui

Investigator Title: Attending neonatologist

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: ongoing caffeine with oxygen supplement (group 1)

Type: Experimental

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.

Label: discontinuing caffeine with oxygen supplement (group 2)

Type: Active Comparator

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

Acronym DCAP
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Investigator, Outcomes Assessor)

Masking Description: Randomization will be performed by someone who are not involved in this study. Outcomes assessor will review the patients' medical record masked for the type of intervention.The investigators performing the final statistic analyses will also be blinded to the treatment allocation.

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