Target Weaning Oxygen to Determine Cafffeine Duration for AOP
DCAP
1 other identifier
interventional
310
1 country
41
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started May 2021
Typical duration for phase_4
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 30, 2021
CompletedStudy Start
First participant enrolled
May 1, 2021
CompletedFirst Posted
Study publicly available on registry
May 3, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 15, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
October 15, 2023
CompletedOctober 18, 2023
October 1, 2023
2.5 years
March 30, 2021
October 16, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
recurrence of apnea of prematurity (RAP)
Either of the following condition is defined as a RAP event: 1. heart rate \<100 beats/min; 2. weak respiratory effort requiring mask-bag ventilation; 3. A high-flow nasal cannula (HFNC) and various noninvasive and invasive ventilation are dictated by the clinical condition, where HFNC is defined as the oxygen flow is ≥2L/min; 4. Restarted caffeine therapy is considered at the discretion of the healthcare team.
from date of randomization until the date of discharge, assessed up to 100 days of life
duration of oxygen supplement after randomization
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
duration of hospital stay after randomization
from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary Outcomes (7)
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
- +2 more secondary outcomes
Study Arms (2)
ongoing caffeine with oxygen supplement (group 1)
EXPERIMENTALsamples 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.
discontinuing caffeine with oxygen supplement (group 2)
ACTIVE COMPARATORsamples assigned to the "discontinuing caffeine with oxygen supplement (group 2)" will discontinue caffeine immediately after randomization, while oxygen supplement is going on.
Interventions
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
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (41)
The First Affiliated Hospital of USTC（University of Science and Technology of China）
Hefei, Anhui, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
Yuan Shi
Chongqing, Chongqing Municipality, 400014, China
First Affiliated Hospital of Army Military Medical University
Chongqing, Chongqing Municipality, China
Fuling Central Hospital of Chongqing City
Fuling, Chongqing Municipality, China
The People's Hospital of Dazu
Longgang, Chongqing Municipality, China
Chongqing University Three Gorges Hospital
Wanzhou, Chongqing Municipality, China
Chongqing Wanzhou Health Center for Women And Children
Wanzhou, Chongqing Municipality, China
Fuzhou Children's Hospital of Fujian Medical University
Fuzhou, Fujian, China
Xiamen Children's Hospital
Xiamen, Fujian, China
Lanzhou University Second Hospital
Lanzhou, Gansu, China
Dongguan City Maternal&Child Health Hospital
Dongguan, Guangdong, China
Maternal and Child Health Hospital of Yunfu
Yunfu, Guangdong, China
Affiliated Hospital Of Guangdong Medical University
Zhanjiang, Guangdong, China
BOAI hospital of Zhongshan
Zhongshan, Guangdong, China
Haikou Hospital of the Maternal and Child Health
Haikou, Hainan, China
The Second Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
The Third Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Hunan Children's Hospital
Changsha, Hunan, China
Hengyang Maternity and Child care hospital
Hengyang, Hunan, China
Children's Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
First Affiliation Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
The first bethune hospital of Jilin university
Changchun, Jilin, China
Qilu Children's Hospital of ShanDong University
Jinan, Shandong, China
Women & Children's Health Care Hospital of Linyi
Linyi, Shandong, China
Shanghai Children's Medical Center
Shanghai, Shanghai Municipality, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, China
Guangyuan central hospital
Guangyuan, Sichuan, China
People's Hospital Of Leshan
Leshan, Sichuan, China
Hospital T. C. M Affiliated to Southwest Medical University
Luzhou, Sichuan, China
Mianyang Central Hospital
Mianyang, Sichuan, China
Panzhihua Central Hospital
Panzhihua, Sichuan, China
The Second People's Hospital of Yibin
Yibin, Sichuan, China
Kunming Children's Hospital
Kunming, Yunnan, China
The Second Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, China
Qujing City Maternal and Child Health Hospital
Qujing, Yunnan, China
The People's Hosiptal of Wenshan Prefecture
Wenshan, Yunnan, China
The First People's Hospital of Zhaotong
Zhaotong, Yunnan, China
Ningbo Women & Children's Hospital
Ningbo, Zhejiang, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Yuan Shi
Children's Hospital of Chongqing Medical University
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- 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.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Attending neonatologist
Study Record Dates
First Submitted
March 30, 2021
First Posted
May 3, 2021
Study Start
May 1, 2021
Primary Completion
October 15, 2023
Study Completion
October 15, 2023
Last Updated
October 18, 2023
Record last verified: 2023-10