Target Weaning Oxygen to Determine Cafffeine Duration for AOP

Caffeine Clinical Trial

— DCAP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04868565
• Other study ID #: 20210326
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2021
• Est. completion date: October 15, 2023

Study information

• Verified date: October 2023
• Source: Children's Hospital of Chongqing Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 310
• Est. completion date: October 15, 2023
• Est. primary completion date: October 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Days to 6 Months

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Apnea of Prematurity
• Caffeine
• Premature Birth

Intervention

Drug:
• Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]
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.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The first bethune hospital of Jilin university	Changchun	Jilin
China	Hunan Children's Hospital	Changsha	Hunan
China	First Affiliated Hospital of Army Military Medical University	Chongqing	Chongqing
China	Yuan Shi	Chongqing	Chongqing
China	The People's Hospital of Dazu	Dazu	Chongqing
China	Dongguan City Maternal&Child Health Hospital	Dongguan	Guangdong
China	Fuling Central Hospital of Chongqing City	Fuling	Chongqing
China	Fuzhou Children's Hospital of Fujian Medical University	Fuzhou	Fujian
China	Guangyuan central hospital	Guangyuan	Sichuan
China	Haikou Hospital of the Maternal and Child Health	Haikou	Hainan
China	The First Affiliated Hospital of USTC(University of Science and Technology of China)	Hefei	Anhui
China	Hengyang Maternity and Child care hospital	Hengyang	Hunan
China	Qilu Children's Hospital of ShanDong University	Jinan	Shandong
China	Kunming Children's Hospital	Kunming	Yunnan
China	The Second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	People's Hospital Of Leshan	Leshan	Sichuan
China	Women & Children's Health Care Hospital of Linyi	Linyi	Shandong
China	Hospital T. C. M Affiliated to Southwest Medical University	Luzhou	Sichuan
China	Mianyang Central Hospital	Mianyang	Sichuan
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Children's Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	First Affiliation Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Ningbo Women & Children's Hospital	Ningbo	Zhejiang
China	Panzhihua Central Hospital	Panzhihua	Sichuan
China	Qujing City Maternal and Child Health Hospital	Qujing	Yunnan
China	Shanghai Children's Medical Center	Shanghai	Shanghai
China	Chongqing University Three Gorges Hospital	Wanzhou	Chongqing
China	Chongqing Wanzhou Health Center for Women And Children	Wanzhou	Chongqing
China	The People's Hosiptal of Wenshan Prefecture	Wenshan	Yunnan
China	Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Xiamen Children's Hospital	Xiamen	Fujian
China	The Second People's Hospital of Yibin	Yibin	Sichuan
China	Maternal and Child Health Hospital of Yunfu	Yunfu	Guangdong
China	Affiliated Hospital Of Guangdong Medical University	Zhanjiang	Guangdong
China	The First People's Hospital of Zhaotong	Zhaotong	Yunnan
China	The Second Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	The Third Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	BOAI hospital of Zhongshan	Zhongshan	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Chongqing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	postmenstrual age of discharging home	postmenstrual age at which the infants are discharged home	from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary	onset of bronchopulmonary dysplasia	onset of bronchopulmonary dysplasia, defined by oxygen dependence at the postmenstrual age of 36 weeks.	from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary	severity of bronchopulmonary dysplasia	evaluate the severity of bronchopulmonary dysplasia according to the 2016 NICHD proposed revision	from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary	restart caffine therapy	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.	from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary	restart noninvasive ventilation	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.	from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary	reintubating the patients	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.	from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary	hospitalization cost after randomization	hospitalization cost after randomization, which includes medicine cost (caffeine, and other medicine, respectively), and other healthcare cost	from date of randomization until the date of discharge, assessed up to 100 days of life