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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03842462

Recruitment Status : Recruiting

First Posted : February 15, 2019

Last Update Posted : November 18, 2020

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Xingwang Zhu, Jiulongpo No.1 People's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Preterm Infant	Other: nCPAP Other: NIPPV Other: NHFOV	Not Applicable

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	684 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	NHFOV vs NIPPV vs nCPAP in Preterm Infants With Respiratory Distress Syndrome: A Multi-center, Prospective, Randomized, Controlled Clinical Superior Trial
Actual Study Start Date :	November 1, 2020
Estimated Primary Completion Date :	May 21, 2022
Estimated Study Completion Date :	May 21, 2022

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Respiratory Distress Syndrome, Infant Acute Respiratory Distress Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: nCPAP neonates assigned to the nCPAP group will be started on a pressure of 6 cmH2O( adjust range:6-8 cmH2O) by pure CPAP system , with FiO2 (0.21～0.40)adjusted to target SpO2 from 89% to 94%	Other: nCPAP infants receive primary non-invasive respiratory support by mean of nCPAP
Active Comparator: NIPPV neonates assigned to the NIPPV group will be started with the following parameters: a) positive end-expiratory pressure (PEEP) of 4 cmH2O (can be raised in steps of 1 cmH2O to max 8 cmH2O, according to the oxygenation).b)Peak Inspiratory Pressure (PIP) of15 cmH2O (can be raised in steps of 1 cmH2O to max 25 cmH2O, according to oxygenation,PaCO2 levels and the chest expansion); maximal allowed FiO2 will be 0.40 and SpO2 targets will be 90-95%. c) inspiratory time (IT) will be 0.45 - 0.5 sec (according to clinicians'evaluation of leaks and the appearance of the pressure curve: a small pressure plateau is required and flow may be set accordingly) and rate will be started at30 bpm (can be raised in steps of 5 bpm to max 50 bpm, according to PaCO2 levels).	Other: NIPPV infants receive primary non-invasive respiratory support by mean of NIPPV
Experimental: NHFOV - neonates assigned to NHFOV will be started with the following boundaries, according to available physiological and mechanical data, as suggested elsewhere: a) Paw of 10 cmH2O (can be changed in steps of 1 cmH2O within the range range 5- 16cmH2O); Paw will be titrated (within the range) according to open lung strategy, performing alveolar recruitment. Maximal allowed FiO2 will be 0.40 and SpO2 targets will be 89%-94%. b) frequency of 10Hz(can be changed in steps of 1Hz within the range 8-15Hz). c)Inspiratory time 50% (1:1).[ d)amplitude 25 cmH2O(can be changed in steps of 5 cmH2O within the range 25-50 cmH2O); amplitude will be titrated according to PaCO2.	Other: NHFOV infants receive primary non-invasive respiratory support by mean of NHFOV

Outcome Measures

Primary Outcome Measures :

treatment failure within 72 hours after randomization 72 hours after randomization [ Time Frame: within 72 hours after randomization ]
need for invasive mechanical ventilation

Secondary Outcome Measures :

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

Other Outcome Measures:

Rate of thick secretions causing an airway obstruction. [ Time Frame: during noninvasive respiratory support ]
determined by the treating clinician by the treating clinician
days of hospitalization [ Time Frame: through study completion, an average of 1 year ]
days
duration of noninvasive respiratory support [ Time Frame: duration of noninvasive respiratory support ]
hours
days on supplemental oxygen [ Time Frame: through study completion, an average of 1 year ]
days
need for surfactant and caffeine treatment [ Time Frame: through study completion, an average of 1 year ]
determined by the treating clinician by the treating clinician
in-hospital mortality [ Time Frame: through study completion, an average of 1 year ]
Death
Rate of nasal trauma [ Time Frame: through study completion, an average of 1 year ]
determined by the treating clinician by the treating clinician

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	up to 12 Hours (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03842462

Contacts

Layout table for location contacts

Contact: Xingwang Zhu, MD	15084335697	15084335697@163.com
Contact: Yuan Shi, PhD	13508300283	petshi530@vip.163.com

Locations

Layout table for location information

China, Chongqing
Children's Hospital of Chongqing Medical University	Recruiting
Chongqing, Chongqing, China, 400042
Contact: Lei Bao, MD +8618623298567 cqbl0046@163.com
Chongqing Women and Children Health Hospital	Recruiting
Chongqing, Chongqing, China, 401120
Contact: Xiaoyun Zhong, MD +8613883519380 13883519380@163.com
Chongqing Three Gorges Central Hospital	Recruiting
Chongqing, Chongqing, China, 404100
Contact: Ming Yi, MD +8615178969566 yimingd123@126.com
China, Guizhou
Guiyang Maternity and Child Health Care Hospital	Recruiting
Guiyang, Guizhou, China, 550000
Contact: Ling Liu, PhD 0851-5965786 liulingped@sina.com
China, Henan
Zhengzhou Children's Hospital	Recruiting
Zhengzhou, Henan, China, 450000
Contact: Huiqing Sun, MD 0371-85515555 s_huiqing@sina.com
China, Hunan
Hunan Children's Hospital	Not yet recruiting
Changsha, Hunan, China, 410000
Contact: Xirong Gao, MD 0731-85356114 gaoxirong@126.com
China, Sichuan
Chengdu Women and Children's Central Hospital	Recruiting
Chengdu, Sichuan, China, 610000
Contact: Rong Ju, MD 028-65021687 jurong123@126.com
China, Yunnan
Kunming Children's Hospital, Kunming	Recruiting
Kunming, Yunnan, China, 650000
Contact: Yangfang Li, MD 0871-63309191 lyf61@126.com

Sponsors and Collaborators

Jiulongpo No.1 People's Hospital

Investigators

Layout table for investigator information

Study Chair:	Yuan Shi, PhD	Children's Hospital of Chongqing Medical University

More Information

Layout table for additonal information

Responsible Party:	Xingwang Zhu, Doctor, Jiulongpo No.1 People's Hospital
ClinicalTrials.gov Identifier:	NCT03842462
Other Study ID Numbers:	NHFOV study group
First Posted:	February 15, 2019 Key Record Dates
Last Update Posted:	November 18, 2020
Last Verified:	November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Xingwang Zhu, Jiulongpo No.1 People's Hospital:


Preterm Infant Respiratory distress syndrome nasal continuous positive airway pressure noninvasive intermittent positive airway pressure noninvasive high-frequency oscillatory ventilation

Additional relevant MeSH terms:

Layout table for MeSH terms

Respiratory Distress Syndrome Respiratory Distress Syndrome, Newborn Premature Birth Obstetric Labor, Premature Obstetric Labor Complications Pregnancy Complications	Lung Diseases Respiratory Tract Diseases Respiration Disorders Infant, Premature, Diseases Infant, Newborn, Diseases

To Top