Nasal Intermittent Positive Pressure Ventilation in Premature Infants (NIPPV)

NCT ID: NCT00433212

Last Updated: 2014-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1011 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2011-12-31

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.

Conditions

Respiratory Insufficiency of Prematurity

Keywords

prematurity; respiratory insufficiency; non-invasive ventilation; bronchopulmonary dysplasia; hyaline membrane disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

A

Non-invasive respiratory support via nasal intermittent positive pressure ventilation

Group Type: ACTIVE_COMPARATOR

NIPPV

Intervention Type: DEVICE

Deliver non-invasive respiratory support via ventilator with NIPPV device

B

Non-invasive respiratory support via nasal Continuous Positive Airway Pressure

Group Type: ACTIVE_COMPARATOR

nCPAP

Intervention Type: DEVICE

Deliver non-invasive respiratory support via ventilator with nCPAP device

Interventions

nCPAP

Deliver non-invasive respiratory support via ventilator with nCPAP device

Intervention Type: DEVICE

NIPPV

Deliver non-invasive respiratory support via ventilator with NIPPV device

Intervention Type: DEVICE

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

• Maximum Eligible Age: 28 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haresh Kirpalani, MD, MSc

Role: STUDY_CHAIR

Hamilton Health Sciences Corporation

Brigitte Lemyre, MD

Role: STUDY_DIRECTOR

Children's Hospital of Eastern Ontario

Aaron Chiu, MD

Role: STUDY_DIRECTOR

St. Boniface Hospital

David Millar, MD

Role: STUDY_DIRECTOR

Royal Maternity Hospital, Belfast

Robin S Roberts, MTech

Role: STUDY_DIRECTOR

Hamilton Health Sciences/McMaster University

Bradley Yoder, MD

Role: STUDY_DIRECTOR

University of Utah

Peter H Dijk, MD, PhD

Role: STUDY_DIRECTOR

University Medical Centrum Groningen

Locations

Georgetown University Children's Medical Center

Washington D.C., District of Columbia, United States

The George Washington University Hospital

Washington D.C., District of Columbia, United States

Tufts University Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, United States

Virtua West Jersey Hospital

Voorhees Township, New Jersey, United States

SUNY Downstate Medical Center

Brooklyn, New York, United States

Kings County Hospital

Brooklyn, New York, United States

New York Hospital Queens

Brooklyn, New York, United States

Queens Hospital Center

Jamaica, New York, United States

Brookdale University Hospital & Medical Center

New York, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Pennsylvania Hospital/U. of Pennsylvania

Philadelphia, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

LKH Feldkirch

Feldkirch, , Austria

CHC St. Vincent

Rocourt, , Belgium

St. Boniface General Hospital/University of Manitoba

Winnipeg, Manitoba, Canada

Winnipeg Health Sciences Centre

Winnipeg, Manitoba, Canada

IWK Health Centre

Halifax, Nova Scotia, Canada

McMaster University

Hamilton, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

The Ottawa Hospital General Campus

Ottawa, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Cork University Maternity Hospital

Wilton, Cork, Ireland

Coombe Women's Hospital

Dublin, , Ireland

National Maternity Hospital

Dublin, , Ireland

University Medical Center Groningen/Beatrix Children's Hosp

Groningen, , Netherlands

Princess Amalia Dept of Pediatrics, Isala Clinics

Zwolle, , Netherlands

Hamad Medical Corporation

Doha, , Qatar

KK Women's and Children's Hospital

Singapore, , Singapore

Karolinska University Hospital/Astrid Lingrenn's Children's Hospital

Stockholm, , Sweden

Royal Maternity Hospital

Belfast, Northern Ireland, United Kingdom

University of Leicester

Leicester, , United Kingdom

St. Mary's Hospital

London, , United Kingdom

Countries

Argentina; Brazil; Chile; Germany; United States; Austria; Belgium; Canada; Ireland; Netherlands; Qatar; Singapore; Sweden; United Kingdom

References

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.

Reference Type: RESULT

PMID: 23944299 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29275926 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26162889 (View on PubMed)

Other Identifiers

CIHR MCT-80246

Identifier Type: -

Identifier Source: secondary_id

ISRCTN15233270

Identifier Type: -

Identifier Source: secondary_id

NTG-2007-NIPPV

Identifier Type: -

Identifier Source: org_study_id