A Comparison of Non-invasive Ventilation Methods Used to Prevent Endotracheal Intubation Due to Apnea in Very Low Birth Weight Infants

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT03298035
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.6
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether nasal intermittent positive pressure ventilation (NIPPV) reduces the need for endotracheal intubation in very low birth weight infants with persistent apnea who fail nasal continuous positive airway pressure (NCPAP).

Condition or Disease	Intervention/Treatment	Phase
Apnea of Prematurity	Device: NCPAP as mode for apnea prevention; Device: NIPPV as rescue mode for apnea prevention	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Comparison of Non-invasive Ventilation Methods Used to Prevent Endotracheal Intubation Due to Apnea in Very Low Birth Weight Infants
• Actual Study Start Date: Nov 11, 2017
• Actual Primary Completion Date: Dec 31, 2018
• Actual Study Completion Date: Dec 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: NCPAP as mode for apnea prevention With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.	Device: NCPAP as mode for apnea prevention; With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Experimental: NIPPV as rescue mode for apnea prevention With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	Device: NIPPV as rescue mode for apnea prevention; With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Were Intubated [28 days after randomization]

2. Duration of Intubation [28 days after randomization]

Secondary Outcome Measures

1. Number of Apneic Events [28 days after randomization]

2. Number of Participants With Bronchopulmonary Dysplasia (BPD) [36 weeks corrected gestational age]

3. Number of Participants With Necrotizing Enterocolitis (NEC) [36 weeks corrected gestational age]

4. Number of Participants With Air Leak Disorders [36 weeks corrected gestational age]

   Air leak disorders include pneumothorax and/or pneumomediastinum.

5. Weight Gain [36 weeks corrected gestational age]

6. Length of Hospital Stay [about 10 to 18 weeks]

7. Number of Participants Who Died [until discharge (about 10 to 18 weeks) or death]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Infants born at < 30 weeks gestational age who develop clinically significant apnea while on NCPAP > 6cm H2O or whose team is considering intubation due to apnea. Consider clinically significant apnea as 1 or more events treated with bag-mask ventilation or 3 episodes of apnea requiring stimulation within 1 hour.

• Infants on maximum caffeine therapy (10mg/kg/day)

Exclusion Criteria:

• Major congenital anomalies including congenital heart disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Health Science Center at Houston	Houston	Texas	United States	70030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Claire Beaullieu, MD, The University of Texas Health Science Center, Houston

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 12, 2017

More Information

Publications

None provided.

• Responsible Party: Catherine Claire Beaullieu, Neonatal-Perinatal Medicine Fellow, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT03298035
• Other Study ID Numbers: HSC-MS-17-0458
• First Posted: Sep 29, 2017
• Last Update Posted: Feb 7, 2020
• Last Verified: Jan 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Apnea; Birth Weight

Study Results

Participant Flow

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Period Title: Overall Study
STARTED	10	9
Received Intervention	9	7
COMPLETED	9	7
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention	Total
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.	Total of all reporting groups
Overall Participants	10	9	19
Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	25.8 (0.8)	25.8 (2.2)	25.8 (1.6)
Sex: Female, Male (Count of Participants)
Female	7 70%	2 22.2%	9 47.4%
Male	3 30%	7 77.8%	10 52.6%
Race/Ethnicity, Customized (Count of Participants)
African American	3 30%	4 44.4%	7 36.8%
Asian	2 20%	0 0%	2 10.5%
Causcasian	1 10%	1 11.1%	2 10.5%
Hispanic	4 40%	4 44.4%	8 42.1%
Region of Enrollment (Count of Participants)
United States	10 100%	9 100%	19 100%
Birth Weight (grams) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams]	773 (160.5)	858 (293.4)	835 (313.3)
Weight at Enrollment (grams) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [grams]	920 (286.6)	921 (204.4)	920.6 (236.7)
Corrected Gestational Age (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	28.4 (2.5)	28.4 (1.1)	28.4 (2.0)
Number of Participants with Antenatal Glucocorticoid Exposure (Count of Participants)
Count of Participants [Participants]	5 50%	3 33.3%	8 42.1%
Number of Participants Who Received Surfactant (Count of Participants)
Count of Participants [Participants]	7 70%	6 66.7%	13 68.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Were Intubated
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	10	9
Count of Participants [Participants]	6 60%	8 88.9%

2. Primary Outcome

Title	Duration of Intubation
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	10	9
Mean (Standard Deviation) [days]	10.6 (10.2)	17.5 (11.4)

3. Secondary Outcome

Title	Number of Apneic Events
Time Frame	28 days after randomization

Outcome Measure Data

Analysis Population Description

One participant in the NIPPV group died; therefore, this data was not collected for that participant.

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	9	9
Mean (Standard Deviation) [Number of apneic events]	3.78 (3.42)	6.22 (5.52)

4. Secondary Outcome

Title	Number of Participants With Bronchopulmonary Dysplasia (BPD)
Time Frame	36 weeks corrected gestational age

Outcome Measure Data

Analysis Population Description

One participant in the NIPPV group died; therefore, this data was not collected for that participant.

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	9	9
Count of Participants [Participants]	9 90%	8 88.9%

5. Secondary Outcome

Title	Number of Participants With Necrotizing Enterocolitis (NEC)
Time Frame	36 weeks corrected gestational age

Outcome Measure Data

Analysis Population Description

One participant in the NIPPV group died; therefore, this data was not collected for that participant.

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	9	9
Count of Participants [Participants]	1 10%	5 55.6%

6. Secondary Outcome

Title	Number of Participants With Air Leak Disorders
Description	Air leak disorders include pneumothorax and/or pneumomediastinum.
Time Frame	36 weeks corrected gestational age

Outcome Measure Data

Analysis Population Description

One participant in the NIPPV group died; therefore, this data was not collected for that participant.

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	9	9
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Weight Gain
Time Frame	36 weeks corrected gestational age

Outcome Measure Data

Analysis Population Description

Data were not collected for this outcome measure.

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	0	0

8. Secondary Outcome

Title	Length of Hospital Stay
Time Frame	about 10 to 18 weeks

Outcome Measure Data

Analysis Population Description

One participant in the NIPPV group died; therefore, this data was not collected for that participant.

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	9	9
Mean (Standard Deviation) [days]	136 (57.7)	149 (67.1)

9. Secondary Outcome

Title	Number of Participants Who Died
Time Frame	until discharge (about 10 to 18 weeks) or death

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention	NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.	With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
Measure Participants	10	9
Count of Participants [Participants]	1 10%	0 0%

Adverse Events

Time Frame	28 days. Serious and other adverse events were considered as those specifically occurring during the 28-day intervention period; however, mortality was evaluated over the maximum of an 18 week duration. The patient death that occurred happened to be within the 28-day study period.
Arm/Group Title	NIPPV as Rescue Mode for Apnea Prevention		NCPAP as Mode for Apnea Prevention
Arm/Group Description	With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment. NIPPV as rescue mode for apnea prevention: With recurrence of apneic events, infants will be placed on NIPPV with settings and adjustments per the clinical team's discretion. If apneic events persist despite NIPPV placement and setting adjustments, clinicians may intubate based on clinical judgment.		With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment. NCPAP as mode for apnea prevention: With recurrence of apneic events, infants on NCPAP will have changes made in NCPAP settings per the clinical team's discretion in attempt to prevent future apneic events. If apneic events persist despite NCPAP adjustments, clinicians may intubate based on clinical judgment.
All Cause Mortality
	NIPPV as Rescue Mode for Apnea Prevention		NCPAP as Mode for Apnea Prevention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		0/9 (0%)
Serious Adverse Events
	NIPPV as Rescue Mode for Apnea Prevention		NCPAP as Mode for Apnea Prevention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	NIPPV as Rescue Mode for Apnea Prevention		NCPAP as Mode for Apnea Prevention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)

Limitations/Caveats

This was a pragmatic trial with inherent bias, as blinding was not possible. There was a small sample size (intent was to enroll 50, but only a few of all screened qualified for escalation of care).

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.