Clinical trial NCT03842462: NHFOV vs NIPPV vs nCPAP in Preterm Infants With Respiratory Distress Syndrome
Official title: NHFOV vs NIPPV vs nCPAP in Preterm Infants With Respiratory Distress Syndrome: A Multi-center, Prospective, Randomized, Controlled Clinical Superior Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Preterm Infant
Keywords: Preterm Infant
Respiratory distress syndrome
nasal continuous positive airway pressure
noninvasive intermittent positive airway pressure
noninvasive high-frequency oscillatory ventilation
Lead sponsor: Jiulongpo No.1 People's Hospital
Sponsor class: OTHER
First posted: 2019-02-15
Enrollment: 684
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a prospective, multi-center, three-arms,parallel, randomized, controlled trial with a superiority design,conducted in China. The investigators conduct this multi-centre, randomized, controlled trial to test the hypothesis that NHFOV is more effective than nCPAP or NIPPV in the treatment of respiratory distress syndrome (RDS) in infants with a gestational age of less than 30 weeks or a birth weight of less than 1500g when used as a primary noninvasive ventilation (NIV) mode.

Detailed description: Preterm infants are eligible to the study if they they match the following inclusion criteria: (1) Gestational age (GA) less than 30 weeks or Birth weight less than 1500g; (2) They have a diagnose of RDS, and RDS Silverman score﹥5; (3) Informed parental consent has been obtained.

Neonates will be randomized and assigned either to nCPAP, NIPPV or NHFOV arms with a 1:1:1 ratio, when patients fulfill all inclusion criteria. Randomization cannot be done earlier. Simple randomization will be done according to a computer-generated random number table and will be posted in a specific secured website 24/7 available. Twins will be allocated in the same treatment group. Infants randomized to one arm cannot crossover to the other or vice-versa during the study.

For all the groups, if the fraction of inspired oxygen (FiO2) requirement is persistently higher than 0.35-0.40 per target SpO2 89-94% and/or dyspnoea defined by Silverman score \> 6 after starting the respiratory support, newborns receive Surfactant by "INSURE" technique, involving endotracheal intubation by direct laryngoscopic vision, endotracheal administration of surfactant (Curosurf, Chiesi Pharmaceutics, Parma, Italy) 200 mg/kg and finally extubation.

After the administration of surfactant, if FiO2 requirement is persistently \>0.4 to keep SpO2 89-94% or severe apnea episodes are present (defined as recurrent apnea with \>3 episodes/h associated with heart rate \<100/min or a single episode of apnea requiring bag and mask ventilation within a 24-hour period ) or at the blood gas (arterial or free-flowing capillary blood) PaCO2\>60 mmHg and potential of hydrogen (pH)\<7.20 obtained at least 1 hour after commencement of the assigned treatment, newborns are intubated and mechanically ventilated. For all the newborns enrolled in the study, arterial or free-flowing capillary blood gas is checked every 6-12 hours, a cerebral and cardiac ultrasound screening is performed within 24 hrs. Further controls follow the routine of the ward.

The study intervention (nCPAP, NIPPV or NHFOV) will be stopped when the above-described minimum parameters are reached and maintained for at least 48h with the following: (1) FiO2≤0.25; (2) Silverman score \<3; (3)no apneas or bradycardia without spontaneous recovery.If a baby will desaturate (SpO2\<85% with FiO2\>25%) or has relevant dyspnea (Silverman≧3) or more than 3 apneas/d, the intervention (CPAP, NIPPV or NHFOV) will be restarted for at least 48h and then re-evaluated

Eligibility criteria: Inclusion Criteria:

* Gestational age (GA) of less than 30 weeks or birth weight less than 1500g
* Clinical diagnose of RDS
* Parental consent

Exclusion Criteria:

* Intubated for resuscitation or for other reasons at birth
* Major congenital malformations or known complex congenital heart disease
* No parental consent

Primary outcomes:
measure: treatment failure within 72 hours after randomization 72 hours after randomization
timeFrame: within 72 hours after randomization
Secondary outcomes:
measure: Rate of airleaks(pneumothorax and/or pneumomediastinum) occurred during noninvasive respiratory support
timeFrame: during noninvasive respiratory support
measure: Rate of bronchopulmonary dysplasia
timeFrame: 36 weeks of postmenstrual age
measure: Rate of retinopathy of prematurity (ROP)
timeFrame: Within 6 months after birth
measure: Rate of necrotizing enterocolitis (NEC)
timeFrame: through study completion, an average of 1 year
measure: Rate of intraventricular hemorrhage
timeFrame: through study completion, an average of 1 year
Other outcomes:
measure: Rate of thick secretions causing an airway obstruction.
timeFrame: during noninvasive respiratory support
measure: days of hospitalization
timeFrame: through study completion, an average of 1 year
measure: duration of noninvasive respiratory support
timeFrame: duration of noninvasive respiratory support
measure: days on supplemental oxygen
timeFrame: through study completion, an average of 1 year
measure: need for surfactant and caffeine treatment
timeFrame: through study completion, an average of 1 year
measure: in-hospital mortality
timeFrame: through study completion, an average of 1 year
measure: Rate of nasal trauma
timeFrame: through study completion, an average of 1 year
Locations:
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Women and Children Health Hospital
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Three Gorges Central Hospital
state: Chongqing
city: Guiyang
country: China
facility: Guiyang Maternity and Child Health Care Hospital
state: Guizhou
city: Zhengzhou
country: China
facility: Zhengzhou Children's Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
city: Chengdu
country: China
facility: Chengdu Women and Children's Central Hospital
state: Sichuan
city: Kunming
country: China
facility: Kunming Children's Hospital, Kunming
state: Yunnan
Study officials:
affiliation: Children's Hospital of Chongqing Medical University
name: Yuan Shi, PhD
role: STUDY_CHAIR
References: