Clinical trial NCT00433212: Nasal Intermittent Positive Pressure Ventilation in Premature Infants (NIPPV)
Official title: Efficacy and Safety of NIPPV to Increase Survival Without Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Insufficiency of Prematurity
Keywords: prematurity
respiratory insufficiency
non-invasive ventilation
bronchopulmonary dysplasia
hyaline membrane disease
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2007-02-09
Enrollment: 1011
Sex: ALL
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The machines and oxygen used to help very premature babies breathe can have side-effects, such as bronchopulmonary dysplasia (BPD). Infants with BPD get more complications (a higher death rate, a longer time in intensive care and on assisted ventilation, more hospital readmissions in the first year of life, and more learning problems) than infants who do not develop BPD. Doctors try to remove the tube in the wind-pipe that links the baby to the breathing machine as soon as possible. However, small babies get tired, and still require help to breathe. One of the standard and common techniques to help them breathe without a tube in the wind-pipe is to use simple pressure support, nasal continuous positive airway pressure or nCPAP. This supports breathing a little, but it is often not enough to prevent the need to go back on the breathing machine.

Nasal intermittent positive pressure ventilation (NIPPV) is similar to nCPAP, but also gives some breaths, or extra support, to babies through a small tube in the nose. NIPPV is safe and effective, and already in use as an alternate "standard" therapy.

The main research question: After being weaned from the breathing machine, is NIPPV better than nCPAP in preventing BPD in premature babies weighing 999 grams or less at birth?

Detailed description: The immature lung of extremely low birth weight (ELBW, \< 1000 g) infants is easily damaged by the placement of an endotracheal tube to deliver mechanical ventilation and oxygen. This and the total time of mechanical ventilation contributes to bronchopulmonary dysplasia (BPD). Infants with BPD have an increased risk of later death or neuro-impairment. With the increasing survival of ELBW infants in the NICU, there has been a proportionate increase in the number of infants surviving with BPD.

Following invasive ventilation via an endotracheal tube (ETT), extubation to nasal Continuous Positive Airway Pressure (nCPAP)ventilation is the standard approach. Currently, 40% of infants who are extubated and given nCPAP support fail, and require re-intubation. Previous work suggests that a less invasive respiratory support such as Nasal Intermittent Positive Pressure Ventilation (NIPPV), without an endotracheal tube is less injurious to the lung. NIPPV may thereby reduce the duration of invasive ventilator support, and aid successful early extubation. We hypothesize that the use of NIPPV leads to a higher rate of survival without BPD than standard therapy with nCPAP.

This randomized clinical trial is appropriately powered to compare NIPPV with nCPAP to detect effects on clinically relevant long-term outcomes, such as death and BPD at 36 weeks. This is a multi-national, randomized, open clinical trial of two different standard methods of providing non-invasive respiratory support to 1000 extremely preterm infants weighing less than 1000 grams at birth.

Eligibility criteria: Inclusion Criteria:

* Birth weight \<1000 gm
* Gestational age \<30 completed weeks
* Intention to manage the infant with non-invasive respiratory support (i.e. no endotracheal tube), where either:

  * the infant is within the first 7 days of life and has never been intubated or has received less than 24 hours of total cumulative intubated respiratory support;
  * the infant is within the first 28 days of life, has been managed with intubated respiratory support for 24 hours or more and is a candidate for extubation followed by non-invasive respiratory support.

Exclusion Criteria:

* Considered non-viable by clinician (decision not to administer effective therapies)
* Life-threatening congenital abnormalities including congenital heart disease (excluding patent ductus arteriosis)
* Infants known to require surgical treatment
* Abnormalities of the upper and lower airways
* Neuromuscular disorders
* Infants who are \>28 days old and continue to require mechanical ventilation with an endotracheal tube

Primary outcomes:
measure: Composite of survival to 36 weeks gestational age, free of moderate-severe bronchopulmonary dysplasia
timeFrame: 36 weeks gestational age
Secondary outcomes:
measure: All cause mortality at 36 weeks gestational age
timeFrame: 36 weeks gestational age
measure: All cause mortality before first discharge home
timeFrame: first discharge home
measure: retinopathy of prematurity
timeFrame: discharge home
measure: ultrasonographic evidence of brain injury
timeFrame: 36 weeks gestional age
measure: necrotizing enterocolitis
timeFrame: 36 weeks gestational age
measure: growth
timeFrame: discharge home
measure: time to establish full feeds
timeFrame: discharge home
measure: nosocomial infections
timeFrame: discharge home
measure: need for re-intubation
timeFrame: 36 weeks gestational age
measure: time on supplemental oxygen
timeFrame: discharge home
measure: duration of positive pressure respiratory support
timeFrame: discharge home
measure: comparison of synchronized and non-synchronized NIPPV
timeFrame: discharge home
measure: bronchopulmonary dysplasia
timeFrame: 36 weeks gestational age
measure: air leak syndromes
timeFrame: 36 weeks gestational age
measure: nasal trauma
timeFrame: discharge home
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Children's Medical Center
state: District of Columbia
city: Washington
country: United States
facility: The George Washington University Hospital
state: District of Columbia
city: Boston
country: United States
facility: Tufts University Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (BIDMC)
state: Massachusetts
city: Voorhees
country: United States
facility: Virtua West Jersey Hospital
state: New Jersey
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Brooklyn
country: United States
facility: Kings County Hospital
state: New York
city: Brooklyn
country: United States
facility: New York Hospital Queens
state: New York
city: Jamaica
country: United States
facility: Queens Hospital Center
state: New York
city: New York
country: United States
facility: Brookdale University Hospital & Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Pennsylvania Hospital/U. of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Feldkirch
country: Austria
facility: LKH Feldkirch
city: Rocourt
country: Belgium
facility: CHC St. Vincent
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital/University of Manitoba
state: Manitoba
city: Winnipeg
country: Canada
facility: Winnipeg Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital General Campus
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Wilton
country: Ireland
facility: Cork University Maternity Hospital
state: Cork
city: Dublin
country: Ireland
facility: Coombe Women's Hospital
city: Dublin
country: Ireland
facility: National Maternity Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen/Beatrix Children's Hosp
city: Zwolle
country: Netherlands
facility: Princess Amalia Dept of Pediatrics, Isala Clinics
city: Doha
country: Qatar
facility: Hamad Medical Corporation
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital/Astrid Lingrenn's Children's Hospital
city: Belfast
country: United Kingdom
facility: Royal Maternity Hospital
state: Northern Ireland
city: Leicester
country: United Kingdom
facility: University of Leicester
city: London
country: United Kingdom
facility: St. Mary's Hospital
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Haresh Kirpalani, MD, MSc
role: STUDY_CHAIR
affiliation: Children's Hospital of Eastern Ontario
name: Brigitte Lemyre, MD
role: STUDY_DIRECTOR
affiliation: St. Boniface Hospital
name: Aaron Chiu, MD
role: STUDY_DIRECTOR
affiliation: Royal Maternity Hospital, Belfast
name: David Millar, MD
role: STUDY_DIRECTOR
affiliation: Hamilton Health Sciences/McMaster University
name: Robin S Roberts, MTech
role: STUDY_DIRECTOR
affiliation: University of Utah
name: Bradley Yoder, MD
role: STUDY_DIRECTOR
affiliation: University Medical Centrum Groningen
name: Peter H Dijk, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A, Roberts RS; NIPPV Study Group. A trial comparing noninvasive ventilation strategies in preterm infants. N Engl J Med. 2013 Aug 15;369(7):611-20. doi: 10.1056/NEJMoa1214533.
citation: Bamat NA, Guevara JP, Bryan M, Roberts RS, Yoder BA, Lemyre B, Chiu A, Millar D, Kirpalani H. Variation in Positive End-Expiratory Pressure Levels for Mechanically Ventilated Extremely Low Birth Weight Infants. J Pediatr. 2018 Mar;194:28-33.e5. doi: 10.1016/j.jpeds.2017.10.065. Epub 2017 Dec 22.
citation: Millar D, Lemyre B, Kirpalani H, Chiu A, Yoder BA, Roberts RS. A comparison of bilevel and ventilator-delivered non-invasive respiratory support. Arch Dis Child Fetal Neonatal Ed. 2016 Jan;101(1):F21-5. doi: 10.1136/archdischild-2014-308123. Epub 2015 Jul 10.