Nasal Intermittent Positive Pressure Ventilation in Premature Infants (NIPPV) (NIPPV)

Efficacy and Safety of NIPPV to Increase Survival Without Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants

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?

Study Overview

• Status: Completed
• Conditions: Respiratory Insufficiency of Prematurity
• Intervention / Treatment: Device: NIPPV; Device: nCPAP

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.

• Study Type: Interventional
• Enrollment (Actual): 1011
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria, 6800
    • LKH Feldkirch
• Belgium
  • Rocourt, Belgium, B-4000
    • CHC St. Vincent
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Winnipeg Health Sciences Centre
    • Winnipeg, Manitoba, Canada, R3E 0L8
      • St. Boniface General Hospital/University of Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4J9
      • McMaster University
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital General Campus
    • Toronto, Ontario, Canada
      • Hospital for Sick Children
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • Royal University Hospital
• Ireland
  • Dublin, Ireland
    • National Maternity Hospital
  • Dublin, Ireland
    • Coombe Women's Hospital
  • Cork
    • Wilton, Cork, Ireland
      • Cork University Maternity Hospital
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen/Beatrix Children's Hosp
  • Zwolle, Netherlands, 8000 GK
    • Princess Amalia Dept of Pediatrics, Isala Clinics
• Qatar
  • Doha, Qatar
    • Hamad medical corporation
• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital
• Sweden
  • Stockholm, Sweden, S-171 76
    • Karolinska University Hospital/Astrid Lingrenn's Children's Hospital
• United Kingdom
  • Leicester, United Kingdom, LE1 6TP
    • University of Leicester
  • London, United Kingdom, W2 1NY
    • St. Mary's Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT12 6BB
      • Royal Maternity Hospital
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The George Washington University Hospital
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Children's Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (BIDMC)
    • Boston, Massachusetts, United States, 02111
      • Tufts University Medical Center
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital
  • New York
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital
    • Brooklyn, New York, United States, 11023
      • SUNY Downstate Medical Center
    • Brooklyn, New York, United States, 11355
      • New York Hospital Queens
    • Jamaica, New York, United States, 11432
      • Queens Hospital Center
    • New York, New York, United States, 11212
      • Brookdale University Hospital & Medical Center
    • Stony Brook, New York, United States, 11794-8111
      • Stony Brook University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19035
      • Pennsylvania Hospital/U. of Pennsylvania
  • Utah
    • Salt Lake City, Utah, United States, 84158-1289
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Non-invasive respiratory support via nasal intermittent positive pressure ventilation	Device: NIPPV; Deliver non-invasive respiratory support via ventilator with NIPPV device
Active Comparator: B; Non-invasive respiratory support via nasal Continuous Positive Airway Pressure	Device: nCPAP; Deliver non-invasive respiratory support via ventilator with nCPAP device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of survival to 36 weeks gestational age, free of moderate-severe bronchopulmonary dysplasia	36 weeks gestational age

Secondary Outcome Measures

Outcome Measure	Time Frame
All cause mortality at 36 weeks gestational age	36 weeks gestational age
retinopathy of prematurity	discharge home
All cause mortality before first discharge home	first discharge home
ultrasonographic evidence of brain injury	36 weeks gestional age
necrotizing enterocolitis	36 weeks gestational age
growth	discharge home
time to establish full feeds	discharge home
nosocomial infections	discharge home
need for re-intubation	36 weeks gestational age
time on supplemental oxygen	discharge home
duration of positive pressure respiratory support	discharge home
comparison of synchronized and non-synchronized NIPPV	discharge home
bronchopulmonary dysplasia	36 weeks gestational age
air leak syndromes	36 weeks gestational age
nasal trauma	discharge home

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Study Chair: Haresh Kirpalani, MD, MSc, Hamilton Health Sciences Corporation; Study Director: Brigitte Lemyre, MD, Children's Hospital of Eastern Ontario; Study Director: Aaron Chiu, MD, St. Boniface Hospital; Study Director: David Millar, MD, Royal Maternity Hospital, Belfast; Study Director: Robin S Roberts, MTech, Hamilton Health Sciences/McMaster University; Study Director: Bradley Yoder, MD, University of Utah; Study Director: Peter H Dijk, MD, PhD, University Medical Centrum Groningen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 7, 2007
• First Submitted That Met QC Criteria: February 8, 2007
• First Posted (Estimate): February 9, 2007

Study Record Updates

• Last Update Posted (Estimate): December 5, 2014
• Last Update Submitted That Met QC Criteria: December 3, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: prematurity; bronchopulmonary dysplasia; respiratory insufficiency; non-invasive ventilation; hyaline membrane disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Respiratory Insufficiency; Premature Birth; Bronchopulmonary Dysplasia
• Other Study ID Numbers: NTG-2007-NIPPV; CIHR MCT-80246; ISRCTN15233270