NHFOV Versus NCPAP to Prevent Exubation Failure

Nasal High Frequency Oscillatory Ventilation (NHFOV) Versus Nasal Continuous Positive Airway Pressure (NCPAP) Ventilation: a Pilot Trial

The purpose of the study is to assess whether nasal high frequency ventilation (NHFV) is superior to nasal continuous positive pressure (nCPAP) to prevent tracheal intubation and mechanical ventilation in preterm infants less than 28 weeks gestation following first attempt at extubation and removal from mechanical ventilation

Study Overview

• Status: Suspended
• Conditions: Respiratory Distress Syndrome
• Intervention / Treatment: Device: CPAP; Device: NHFOV

Detailed Description

Extremely preterm infants frequently need to be placed back on invasive mechanical ventilation following initial attempts to remove them from this mode of respiratory support. Continued mechanical ventilation is thought to be the primary driver in the development of chronic lung disease and a major component in adverse developmental outcome of these infants. Infants fail their first trial of removal from ventilation because of apnea and respiratory failure. Animal studies and early clinical experience suggest that it is possible to effectively provide ventilation via high frequency nasal ventilation. In the animal models this mode of ventilation appears to provide for better lung development and less injury.

Nasal CPAP has been shown to improve the success rate of extubation from mechanical ventilation by preventing post extubation atelectasis with resultant improvements in gas exchange. However in many of the most premature infants, poorly developed control of respiratory drive is a major problem and despite treatment with caffeine, mechanical ventilation is needed. High frequency nasal ventilation may support ventilation enough during apneic periods to mitigate the need for traditional mechanical ventilation. Use of non-invasive modes may result in a decrease in the incidence and or severity of chronic lung problems and developmental disability of this group of infants.

Extremely premature infants (GA <28 weeks) less than 7 days old will be randomized to either NHFV or nCPAP following the first attempt at extubation and removal from mechanical ventilation. All infants will have received at least a loading dose of caffeine citrate (10 mg/kg of caffeine base equivalent prior to extubation. Initial nCPAP level will be determined by clinical staff but will be at least equal to the level of positive end expiratory pressure (PEEP) used during mechanical ventilation. A similar level of pressure will be used as initial mean airway pressure (MAP) in infants receiving HFNV.

The primary outcome will be need for reintubation during the first 7 days after extubation attempt due to preset criteria. Crossover to the other modality will not be allowed during this period. Infants may remain on HFNF beyond the 7 day primary endpoint if deemed necessary by the clinical staff. Weaning of HFNV to nCPAP will be allowed during the 7 day primary study period and reinstitution of HFNF will be allowed for those initially randomized to that mode of respiratory support.

The magnitude of the effect size cannot be determined as there are no studies to base a sample size calculation on. A pragmatic sample size of 20 infants was selected (10 in each arm) to allow estimation of any potential effect size. Further study(ies) will need to be performed to show conclusively efficacy (or lack) of NHFV to prevent post-extubation respiratory failure or its use in preventing chronic lung disease or improving developmental outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
    • Winnipeg, Manitoba, Canada, R3A 1S1
      • Health Sciences Center, NICU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 minutes to 1 week (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newborn less than 28 weeks gestation at birth
• Intubated and ventilated in the first 24 hours of life
• Extubated in the first week of life
• Parental consent

Exclusion Criteria:

• Lack of parental consent
• Major congenital malformation
• Severe perinatal asphyxia
• Airway abnormalities
• Pneumothorax

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nasal CPAP; Nasal CPAP using Infant flow	Device: CPAP; Nasal Continuous Positive Airway Pressure Ventilation using Infant Flow CPAP machine
Experimental: NHFOV; Nasal High Frequency Oscillatory Ventilation using Dräger Babylog® VN500 ventilator machine	Device: NHFOV; Nasal High Frequency Oscillatory Ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extubation failure	Newborns in both groups will be re-intubated within the study period if they have respiratory failure defined as arterial or capillary gas with pH < 7.20 or PCO2 > 60, oxygen requirement ≥ 35%, or recurrent or severe apnea (12 documented apneas within 24 hours or single apnea requiring positive pressure ventilation).	within 7 days post-extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in capillary pCO2 after extubation	capillary pCO2 values will be measured after extubation. Timing and frequency of blood gas sampling will be determined by clinical staff caring for infant and will not be specified by study protocol.	Within 7 days post-extubation
pneumothorax	incidence of pneumothorax during use of either nasal CPAP or high frequency nasal ventilation will be documented.	duration of use of positive pressure or reintubation which ever is shorter
intraventricular hemorrage (IVH)	Infants will be screened for IVH per routine clinical care. Incidence of total IVH and severe IVH will be compared between treatments.	first 2 weeks of life
feeding tolerance	The time to achieve full enteral feeding (135 ml/kg/d) will be compared for both treatments	3 weeks

Collaborators and Investigators

• Sponsor: University of Manitoba
• Investigators: Study Director: Ronald J Baier, M.D., HSC Neonatology

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: April 17, 2013
• First Submitted That Met QC Criteria: May 9, 2013
• First Posted (Estimate): May 14, 2013

Study Record Updates

• Last Update Posted (Estimate): August 5, 2015
• Last Update Submitted That Met QC Criteria: August 3, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: RDS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: B2013: 040