Nasal Intermittent Positive Pressure Ventilation in Premature Infants (NIPPV)

Respiratory Insufficiency of Prematurity Clinical Trial

— NIPPV  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00433212
• Other study ID #: NTG-2007-NIPPV
• Secondary ID: CIHR MCT-80246IS
• Status: Completed
• Phase: Phase 3
• First received: February 7, 2007
• Last updated: December 3, 2014
• Start date: April 2007
• Est. completion date: December 2011

Study information

• Verified date: December 2014
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1011
• Est. completion date: December 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 28 Days

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Premature Birth
• Pulmonary Valve Insufficiency
• Respiratory Insufficiency
• Respiratory Insufficiency of Prematurity

Intervention

Device:
• nCPAP
Deliver non-invasive respiratory support via ventilator with nCPAP device
• NIPPV
Deliver non-invasive respiratory support via ventilator with NIPPV device

Locations

Country	Name	City	State
Austria	LKH Feldkirch	Feldkirch
Belgium	CHC St. Vincent	Rocourt
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	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	St. Boniface General Hospital/University of Manitoba	Winnipeg	Manitoba
Canada	Winnipeg Health Sciences Centre	Winnipeg	Manitoba
Ireland	Coombe Women's Hospital	Dublin
Ireland	National Maternity Hospital	Dublin
Ireland	Cork University Maternity Hospital	Wilton	Cork
Netherlands	University Medical Center Groningen/Beatrix Children's Hosp	Groningen
Netherlands	Princess Amalia Dept of Pediatrics, Isala Clinics	Zwolle
Qatar	Hamad Medical Corporation	Doha
Singapore	KK Women's and Children's Hospital	Singapore
Sweden	Karolinska University Hospital/Astrid Lingrenn's Children's Hospital	Stockholm
United Kingdom	Royal Maternity Hospital	Belfast	Northern Ireland
United Kingdom	University of Leicester	Leicester
United Kingdom	St. Mary's Hospital	London
United States	Beth Israel Deaconess Medical Center (BIDMC)	Boston	Massachusetts
United States	Tufts University Medical Center	Boston	Massachusetts
United States	Kings County Hospital	Brooklyn	New York
United States	New York Hospital Queens	Brooklyn	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	Queens Hospital Center	Jamaica	New York
United States	Brookdale University Hospital & Medical Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Pennsylvania Hospital/U. of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Virtua West Jersey Hospital	Voorhees	New Jersey
United States	Georgetown University Children's Medical Center	Washington	District of Columbia
United States	The George Washington University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Ireland,  Netherlands,  Qatar,  Singapore,  Sweden,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of survival to 36 weeks gestational age, free of moderate-severe bronchopulmonary dysplasia		36 weeks gestational age	Yes
Secondary	All cause mortality at 36 weeks gestational age		36 weeks gestational age	Yes
Secondary	All cause mortality before first discharge home		first discharge home	Yes
Secondary	retinopathy of prematurity		discharge home	Yes
Secondary	ultrasonographic evidence of brain injury		36 weeks gestional age	Yes
Secondary	necrotizing enterocolitis		36 weeks gestational age	Yes
Secondary	growth		discharge home	Yes
Secondary	time to establish full feeds		discharge home	Yes
Secondary	nosocomial infections		discharge home	No
Secondary	need for re-intubation		36 weeks gestational age	Yes
Secondary	time on supplemental oxygen		discharge home	No
Secondary	duration of positive pressure respiratory support		discharge home	Yes
Secondary	comparison of synchronized and non-synchronized NIPPV		discharge home	No
Secondary	bronchopulmonary dysplasia		36 weeks gestational age	Yes
Secondary	air leak syndromes		36 weeks gestational age	Yes
Secondary	nasal trauma		discharge home	Yes