Target Weaning Oxygen to Determine Cafffeine Duration for AOP
- Conditions
- Weaning OxygenMedicine RegimenApnea of PrematurityCaffeine
- Interventions
- Registration Number
- NCT04868565
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 310
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description discontinuing caffeine with oxygen supplement (group 2) Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT] samples assigned to the "discontinuing caffeine with oxygen supplement (group 2)" will discontinue caffeine immediately after randomization, while oxygen supplement is going on. ongoing caffeine with oxygen supplement (group 1) Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT] 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.
- Primary Outcome Measures
Name Time Method duration of hospital stay after randomization from date of randomization until the date of discharge, assessed up to 100 days of life duration of hospital stay after randomization
recurrence of apnea of prematurity (RAP) from date of randomization until the date of discharge, assessed up to 100 days of life 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.
duration of oxygen supplement after randomization from date of randomization until the date of discharge, assessed up to 100 days of life duration of oxygen supplement after randomization
- Secondary Outcome Measures
Name Time Method postmenstrual age of discharging home from date of randomization until the date of discharge, assessed up to 100 days of life postmenstrual age at which the infants are discharged home
onset of bronchopulmonary dysplasia from date of randomization until the date of discharge, assessed up to 100 days of life onset of bronchopulmonary dysplasia, defined by oxygen dependence at the postmenstrual age of 36 weeks.
restart caffine therapy from date of randomization until the date of discharge, assessed up to 100 days of life either of the following condition considers restarting caffeine therapy: 1. RAP event requires additional interventions to positioning, suction, and tactile stimulation; 2. intermittent hypoxemia ≥ 5 episodes per day where intermittent hypoxemia is referred to as a transient desaturation with Saturation \<90%, but without bradycardia; 3. restart caffeine therapy at the discretion of the healthcare team.
severity of bronchopulmonary dysplasia from date of randomization until the date of discharge, assessed up to 100 days of life evaluate the severity of bronchopulmonary dysplasia according to the 2016 NICHD proposed revision
restart noninvasive ventilation from date of randomization until the date of discharge, assessed up to 100 days of life either of the following conditions considers restarting non-invasive ventilation: 1.patients exhibit severe respiratory distress, including but not limited to tachypnea, chest indrawing, and grunting; 2. In the setting of nasal cannula oxygen supplemental, PaO2\<50mmHg or SpO2\<90% at the effective FiO2≥30%； 3. In the setting of incubator oxygen or hood oxygen supplement, PaO2\<50mmHg or SpO2\<90% at effective FiO2≥30% at the measured FiO2≥30%；4. Restart non-invasive ventilation at the discretion of the healthcare team.
reintubating the patients from date of randomization until the date of discharge, assessed up to 100 days of life Either of the following conditions considers reintubating the patients: 1. Severe respiratory acidosis with PaCO2\>65 mmHg and pH\<7.2; 2. Refractory hypoxemia at maximal setting in the non-invasive ventilation ( SpO2\< 90%, with FiO2=0.4，and PEEP reaching eight cmH2O in CPAP/NIPPV，or Paw reaching 16 cmH2O in NHFOV; 3. Severe pulmonary hemorrhage; 4. Frequent apneic episodes (≥3 episodes per hour), or at least one episode within the last 24hours requiring mask-bag ventilation, which does not respond well to methylxanthine; 5. Hemodynamic instability after a recent occurrence of neonatal resuscitation; 6. Reintubating the patients at the discretion of the healthcare team.
hospitalization cost after randomization from date of randomization until the date of discharge, assessed up to 100 days of life hospitalization cost after randomization, which includes medicine cost (caffeine, and other medicine, respectively), and other healthcare cost
Trial Locations
- Locations (41)
The First Affiliated Hospital of USTC（University of Science and Technology of China）
🇨🇳Hefei, Anhui, China
Dongguan City Maternal&Child Health Hospital
🇨🇳Dongguan, Guangdong, China
Haikou Hospital of the Maternal and Child Health
🇨🇳Haikou, Hainan, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
The Third Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Hengyang Maternity and Child care hospital
🇨🇳Hengyang, Hunan, China
Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Women & Children's Health Care Hospital of Linyi
🇨🇳Linyi, Shandong, China
Kunming Children's Hospital
🇨🇳Kunming, Yunnan, China
Shanghai Children's Medical Center
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
The Second Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
Guangyuan central hospital
🇨🇳Guangyuan, Sichuan, China
The People's Hosiptal of Wenshan Prefecture
🇨🇳Wenshan, Yunnan, China
The first bethune hospital of Jilin university
🇨🇳Changchun, Jilin, China
People's Hospital Of Leshan
🇨🇳Leshan, Sichuan, China
Yuan Shi
🇨🇳Chongqing, Chongqing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Fuling Central Hospital of Chongqing City
🇨🇳Fuling, Chongqing, China
First Affiliated Hospital of Army Military Medical University
🇨🇳Chongqing, Chongqing, China
Chongqing University Three Gorges Hospital
🇨🇳Wanzhou, Chongqing, China
Chongqing Wanzhou Health Center for Women And Children
🇨🇳Wanzhou, Chongqing, China
Xiamen Children's Hospital
🇨🇳Xiamen, Fujian, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, Gansu, China
The People's Hospital of Dazu
🇨🇳Dazu, Chongqing, China
Fuzhou Children's Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Affiliated Hospital Of Guangdong Medical University
🇨🇳Zhanjiang, Guangdong, China
The Second Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
BOAI hospital of Zhongshan
🇨🇳Zhongshan, Guangdong, China
Maternal and Child Health Hospital of Yunfu
🇨🇳Yunfu, Guangdong, China
Hunan Children's Hospital
🇨🇳Changsha, Hunan, China
Children's Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
First Affiliation Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
Qilu Children's Hospital of ShanDong University
🇨🇳Jinan, Shandong, China
Mianyang Central Hospital
🇨🇳Mianyang, Sichuan, China
Hospital T. C. M Affiliated to Southwest Medical University
🇨🇳Luzhou, Sichuan, China
Panzhihua Central Hospital
🇨🇳Panzhihua, Sichuan, China
The Second People's Hospital of Yibin
🇨🇳Yibin, Sichuan, China
Qujing City Maternal and Child Health Hospital
🇨🇳Qujing, Yunnan, China
Ningbo Women & Children's Hospital
🇨🇳Ningbo, Zhejiang, China
The First People's Hospital of Zhaotong
🇨🇳Zhaotong, Yunnan, China