NHFOV vs NIPPV vs nCPAP in Preterm Infants With Respiratory Distress Syndrome

Not Applicable

• Conditions: Preterm Infant

• Registration Number: NCT03842462
• Lead Sponsor: Jiulongpo No.1 People's Hospital

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

Study Timeline

• Study First Submitted: 2019-01-31
• Study First Submitted QC: 2019-02-14
• Study First Posted: 2019-02-15
• Status Verified: 2020-11
• Study Start: 2020-11-01
• Last Update Submitted: 2020-11-16
• Last Update Posted: 2020-11-18
• Primary Completion: 2022-05-21
• Study Completion: 2022-05-21

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 684

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
treatment failure within 72 hours after randomization 72 hours after randomization	within 72 hours after randomization	need for invasive mechanical ventilation

Secondary Outcome Measures

Name	Time	Method
Rate of retinopathy of prematurity (ROP)	Within 6 months after birth	≥ 2nd stage
Rate of intraventricular hemorrhage	through study completion, an average of 1 year	≥ 3nd grade
Rate of airleaks(pneumothorax and/or pneumomediastinum) occurred during noninvasive respiratory support	during noninvasive respiratory support	determined by the treating clinician by the treating clinician
Rate of bronchopulmonary dysplasia	36 weeks of postmenstrual age	defined according to the NICHD definition
Rate of necrotizing enterocolitis (NEC)	through study completion, an average of 1 year	≥ 2nd stage

Trial Locations

Locations (8)

Children's Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

Chongqing Women and Children Health Hospital; 🇨🇳 Chongqing, Chongqing, China

Chongqing Three Gorges Central Hospital; 🇨🇳 Chongqing, Chongqing, China

Guiyang Maternity and Child Health Care Hospital; 🇨🇳 Guiyang, Guizhou, China

Zhengzhou Children's Hospital; 🇨🇳 Zhengzhou, Henan, China

Hunan Children's Hospital; 🇨🇳 Changsha, Hunan, China

Chengdu Women and Children's Central Hospital; 🇨🇳 Chengdu, Sichuan, China

Kunming Children's Hospital, Kunming; 🇨🇳 Kunming, Yunnan, China