Apnea of PrematurityPhase 4DCAPNCT04868565
Target Weaning Oxygen to Determine Cafffeine Duration for AOP
A Phase 4 study testing Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT] in people with Apnea of Prematurity and Caffeine, run by Children's Hospital of Chongqing Medical University at 41 sites in China.
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. Read more about this study
- Who is it for?
- Ages 14 days to 6 months
- Conditions the study is for
- Apnea of Prematurity, Caffeine, Weaning Oxygen
- What is being tested?
- Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 310 participants
- Where
- 41 sitesChina
- Study dates
- 1 May 2021to 15 Oct 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 days to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
41 sites in 1 country.
41 sites in 1 country
China41 sites
Peking Union Medical College Hospital
Beijing, Beijing Municipality
The first bethune hospital of Jilin university
Changchun, Jilin
Hunan Children's Hospital
Changsha, Hunan
Yuan Shi
Chongqing, Chongqing Municipality, 400014
First Affiliated Hospital of Army Military Medical University
Chongqing, Chongqing Municipality
Dongguan City Maternal&Child Health Hospital
Dongguan, Guangdong
Fuling Central Hospital of Chongqing City
Fuling, Chongqing Municipality
Fuzhou Children's Hospital of Fujian Medical University
Fuzhou, Fujian
Guangyuan central hospital
Guangyuan, Sichuan
Haikou Hospital of the Maternal and Child Health
Haikou, Hainan
The First Affiliated Hospital of USTC（University of Science and Technology of China）
Hefei, Anhui
Hengyang Maternity and Child care hospital
Hengyang, Hunan
Qilu Children's Hospital of ShanDong University
Jinan, Shandong
Kunming Children's Hospital
Kunming, Yunnan
The Second Affiliated Hospital of Kunming Medical University
Kunming, Yunnan
Lanzhou University Second Hospital
Lanzhou, Gansu
People's Hospital Of Leshan
Leshan, Sichuan
Women & Children's Health Care Hospital of Linyi
Linyi, Shandong
The People's Hospital of Dazu
Longgang, Chongqing Municipality
Hospital T. C. M Affiliated to Southwest Medical University
Luzhou, Sichuan
Mianyang Central Hospital
Mianyang, Sichuan
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi
Children's Hospital of Nanjing Medical University
Nanjing, Jiangsu
First Affiliation Hospital of Nanjing Medical University
Nanjing, Jiangsu
Ningbo Women & Children's Hospital
Ningbo, Zhejiang
Panzhihua Central Hospital
Panzhihua, Sichuan
Qujing City Maternal and Child Health Hospital
Qujing, Yunnan
Shanghai Children's Medical Center
Shanghai, Shanghai Municipality
Chongqing University Three Gorges Hospital
Wanzhou, Chongqing Municipality
Chongqing Wanzhou Health Center for Women And Children
Wanzhou, Chongqing Municipality
The People's Hosiptal of Wenshan Prefecture
Wenshan, Yunnan
Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi
Xiamen Children's Hospital
Xiamen, Fujian
The Second People's Hospital of Yibin
Yibin, Sichuan
Maternal and Child Health Hospital of Yunfu
Yunfu, Guangdong
Affiliated Hospital Of Guangdong Medical University
Zhanjiang, Guangdong
The First People's Hospital of Zhaotong
Zhaotong, Yunnan
The Second Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan
The Third Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan
BOAI hospital of Zhongshan
Zhongshan, Guangdong
About this study
Official title: Target Weaning Oxygen to Determine Duration of Caffeine for Apnea of Prematurity: a Multicenter, Prospective, Randomized Controlled Trial
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.
- Conditions
- Apnea of Prematurity, Caffeine, Weaning Oxygen, Medicine Regimen
- Being tested
- Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]
- Keywords
- apnea of prematurity, caffeine, discontinuation
- Medical subject headings
- Apnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT]Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| ongoing caffeine with oxygen supplement (group 1) | Experimental | 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. Receives: Drug: Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT] |
| discontinuing caffeine with oxygen supplement (group 2) | Active comparator | samples assigned to the "discontinuing caffeine with oxygen supplement (group 2)" will discontinue caffeine immediately after randomization, while oxygen supplement is going on. Receives: Drug: Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT] |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
Secondary outcomes (7)
postmenstrual age of discharging home
postmenstrual age at which the infants are discharged home
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
onset of bronchopulmonary dysplasia
onset of bronchopulmonary dysplasia, defined by oxygen dependence at the postmenstrual age of 36 weeks.
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
severity of bronchopulmonary dysplasia
evaluate the severity of bronchopulmonary dysplasia according to the 2016 NICHD proposed revision
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
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.
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
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.
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
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.
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
hospitalization cost after randomization
hospitalization cost after randomization, which includes medicine cost (caffeine, and other medicine, respectively), and other healthcare cost
Measured: from date of randomization until the date of discharge, assessed up to 100 days of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2021
- Study start1 May 2021
- Primary completion15 Oct 2023
- Study completion15 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Apnea of PrematurityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 310 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Chongqing Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wang Jianhui, Children's Hospital of Chongqing Medical University
- Investigators
- Yuan Shi, Study director, Children's Hospital of Chongqing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04868565
- Sponsor's protocol ID
- 20210326
- Acronym
- DCAP
- Status last verified
- Oct 2023
- First submitted
- 30 Mar 2021
- Last updated
- 18 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Target Weaning Oxygen to Determine Duration of Caffeine for Apnea of Prematurity: a Multicenter, Prospective, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04868565
- Acronym / sponsor ID
- DCAP / 20210326
- Conditions
- Apnea of Prematurity, Caffeine, Weaning Oxygen, Medicine Regimen
- Keywords
- apnea of prematurity, caffeine, discontinuation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 310 participants (actual)
- Lead sponsor
- Children's Hospital of Chongqing Medical UniversityUniversity, hospital or other
- Study start
- 1 May 2021 (actual)
- Primary completion
- 15 Oct 2023 (actual)
- Study completion
- 15 Oct 2023 (actual)
- First posted
- 3 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ongoing caffeine with oxygen supplement (group 1) | Experimental | Drug: 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. |
| discontinuing caffeine with oxygen supplement (group 2) | Active comparator | Drug: 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. |
Who may qualify
- Ages
- 14 days to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | discontinuing caffeine with oxygen supplement (group 2), ongoing caffeine with oxygen supplement (group 1) |
Primary outcome
recurrence of apnea of prematurity (RAP)
Time frame: 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
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
duration of oxygen supplement after randomization
duration of hospital stay after randomization
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
duration of hospital stay after randomization
7 secondary outcomes
postmenstrual age of discharging home
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
onset of bronchopulmonary dysplasia
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
severity of bronchopulmonary dysplasia
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
restart caffine therapy
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
restart noninvasive ventilation
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
reintubating the patients
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
hospitalization cost after randomization
Time frame: from date of randomization until the date of discharge, assessed up to 100 days of life
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuan Shi study director
Children's Hospital of Chongqing Medical University
41 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Caffeine Citrate 20 MG/1 ML Intravenous Solution [CAFCIT] in people with Apnea of Prematurity and Caffeine, run by Children's Hospital of Chongqing Medical University at 41 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
recurrence of apnea of prematurity (RAP) (time frame: from date of randomization until the date of discharge, assessed up to 100 days of life). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2023.