Delivery Room Management Trial of Premature Infants at High Risk of Respiratory Distress Syndrome

• Sponsor: Vermont Oxford Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT00244101
• Collaborator: (none)
• Enrollment: 648
• Location: 1
• Arms: 3
• Duration (Months): 94
• Patients Per Site Per Month: 6.9

Study Details

Study Description

Brief Summary

The best mode of delivery room stabilization for premature infants at high risk for respiratory distress syndrome is unknown. The protocol evaluates the impact of three distinct methods of post-delivery stabilization and subsequent early respiratory care on chronic lung disease and survival in premature infants at high risk for respiratory distress syndrome.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Distress Syndrome, Newborn	Drug: PS Group; Device: NCPAP Group; Drug: ISX Group	Phase 3

Detailed Description

The "Delivery room management of premature infants at high risk of respiratory distress syndrome" protocol compares three distinct methods of post-delivery stabilization and subsequent early respiratory care on chronic lung disease and survival in premature infants at high risk of respiratory distress syndrome. The three approaches to post-delivery care include:

1. Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support.

2. Early stabilization on nasal continuous positive airway pressure (NCPAP) with selective intubation and surfactant administration for clinical indications.

3. Intubation, prophylactic surfactant administration shortly after delivery and rapid extubation to nasal CPAP.

The primary null hypothesis for this study is that no difference will be found in chronic lung disease and/or mortality at 36 weeks adjusted age in premature infants at high risk of RDS, depending on the method of post-delivery stabilization.

The study is a randomized, multicenter trial conducted at participating Vermont Oxford Network Centers. Participating centers will demonstrate competency in the use of nasal CPAP by successfully completing a web-based, educational program and utilizing nasal CPAP in a minimum of 20 infants in their NICU.

Infants likely to be delivered to women presenting to a participating Vermont Oxford Network Center at high risk of premature delivery at gestational age 26 + 0 to 29 + 6 weeks will be eligible for inclusion. Specific inclusion criteria that must be met prior to randomization include:

1. imminent delivery

2. no potentially life-threatening congenital anomaly or genetic syndrome

3. no known lung maturity

4. antenatal steroid status known

5. written and informed consent obtained prior to delivery.

Exclusion criteria will include:

1. stillborn infants (Apgar score of 0 at one minute of age) or

2. infants noted to have a potentially life-threatening congenital anomaly or genetic syndrome noted immediately after delivery.

Eligible infants will have consent obtained prior to delivery. They will be stratified into two groups: 26 + 0 to 27 + 6 weeks gestation and 28 + 0 to 29 + 6 weeks gestation. Shortly before delivery, infants will be randomized to one of the three stabilization strategies detailed below:

1. Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support (PS group).

2. Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications (NCPAP group).

3. Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP (ISX group).

Infants requiring intubation for respiratory failure during this study (in any of the three groups) may be stabilized on either conventional or high-frequency ventilation. Specific criteria regarding target ranges for blood gases and indications for extubation, subsequent surfactant dosing, management of extubation, and criteria for reintubation, are all detailed in the protocol.

The primary outcome measure is chronic lung disease (defined as documented requirement for supplemental oxygen or respiratory support) or mortality at 36 weeks adjusted age. Secondary outcome measures include a variety of clinical outcomes, as well as issues regarding duration of hospital stay and other resource utilization. Long-term outcomes will be measured by a health care questionnaire at two years of age. A sample size of over 895 infants will be required to demonstrate a 25% reduction in the risk of chronic lung disease at 36 weeks adjusted age.

Study Design

• Study Type: Interventional
• Actual Enrollment: 648 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Delivery Room Management of Premature Infants at High Risk of Respiratory Distress Syndrome
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PS Group Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support.	Drug: PS Group; Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support.; Other Names: Prophylactic Surfactant Group
Experimental: NCPAP Group Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications.	Device: NCPAP Group; Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications.; Other Names: Nasal CPAP group
Experimental: ISX Group Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP.	Drug: ISX Group; Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP.; Other Names: Intubation, Surfactant Administration, Extubation to Nasal CPAP. ENSURE.

Outcome Measures

Primary Outcome Measures

1. Death or Chronic Lung Disease [at 36 weeks postmenstrual age]

2. Death [36 weeks adjusted age]

Secondary Outcome Measures

1. Complications of Prematurity [prior to hospital discharge]

2. Days of Ventilator Support [prior to hospital discharge]

3. Days in Hospital [prior to hospital discharge]

4. Parental Questionnaire for Health Status [at 24 months of age]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 26 Weeks to 29 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Infants likely to be delivered to women presenting to a participating Vermont Oxford Network Center at high risk of premature delivery at gestational age 26 + 0 to 29 + 6 weeks will be eligible for inclusion. Specific inclusion criteria that must be met prior to randomization include:

1. Imminent delivery

2. No potentially life-threatening congenital anomaly or genetic syndrome

3. No known lung maturity

4. Antenatal steroid status known

5. Written, informed consent obtained (on admission or prior to delivery).

Exclusion Criteria:

1. Stillborn (Apgar score of 0 at one minute of age)

2. Noted to have a potentially life-threatening congenital anomaly or genetic syndrome noted immediately after delivery.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vermont Oxford Network	Burlington	Vermont	United States	05401

Sponsors and Collaborators

• Vermont Oxford Network

Investigators

• Principal Investigator: Roger F Soll, MD, Director of Clinical Trials, Vermont Oxford Network
• Principal Investigator: Michael Dunn, MD, Chief of Newborn and Developmental Pediatrics, Sunnybrook and Women's Hospital, Toronto, Ontario, Canada

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vermont Oxford Network
• ClinicalTrials.gov Identifier: NCT00244101
• Other Study ID Numbers: CHRMS 03-233
• First Posted: Oct 25, 2005
• Last Update Posted: Sep 14, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Vermont Oxford Network: Prematurity; respiratory distress syndrome; surfactant; nasal continuous positive airway pressure
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Syndrome; Pulmonary Surfactants

Study Results

Participant Flow

Arm/Group Title	PS Group	NCPAP Group	ISX Group
Arm/Group Description	Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support.	Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications.	Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP.
Period Title: Overall Study
STARTED	209	223	216
COMPLETED	209	223	216
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	PS Group	NCPAP Group	ISX Group	Total
Arm/Group Description	Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support.	Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications.	Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP.	Total of all reporting groups
Overall Participants	209	223	216	648
Age (Count of Participants)
<=18 years	209 100%	223 100%	216 100%	648 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.0 (1.1)	28.1 (1.3)	28.1 (1.1)	28.0 (1.1)
Sex: Female, Male (Count of Participants)
Female	118 56.5%	99 44.4%	115 53.2%	332 51.2%
Male	91 43.5%	124 55.6%	101 46.8%	316 48.8%
Region of Enrollment (participants) [Number]
United States	209 100%	223 100%	216 100%	648 100%

Outcome Measures

1. Primary Outcome

Title	Death or Chronic Lung Disease
Time Frame	at 36 weeks postmenstrual age

Outcome Measure Data

Analysis Population Description

intention to treat analysis

Arm/Group Title	PS Group	NCPAP Group	ISX Group
Arm/Group Description	Intubation, prophylactic surfactant administration shortly after delivery, and subsequent stabilization on ventilator support.	Early stabilization on nasal continuous positive airway pressure (NCPAP) with selected intubation and surfactant administration for clinical indications.	Intubation, prophylactic surfactant administration shortly after delivery, and rapid extubation to nasal CPAP.
Measure Participants	209	223	216
Number [participants]	76 36.4%	68 30.5%	62 28.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PS Group, NCPAP Group, ISX Group
	Comments	PS group used as standard of care. Relative risk and 95 % CI calculated for NCPAP group and ISX group compared to PS group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	.365
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: .05
	Estimation Comments

2. Primary Outcome

Title	Death
Time Frame	36 weeks adjusted age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Complications of Prematurity
Time Frame	prior to hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Days of Ventilator Support
Time Frame	prior to hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Days in Hospital
Time Frame	prior to hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Parental Questionnaire for Health Status
Time Frame	at 24 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Prophylactic Surfactant		Surfactant Extubated to nCPAP		NCPAP
Arm/Group Description	Prophylactic surfactant followed by mechanical ventilation		prophylactic surfactant with rapid extubation to bubble nCPAP		initial management with bubble nCPAP and selective surfactant treatment
All Cause Mortality
	Prophylactic Surfactant		Surfactant Extubated to nCPAP		NCPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Prophylactic Surfactant		Surfactant Extubated to nCPAP		NCPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/209 (0%)		0/216 (0%)		0/223 (0%)
Other (Not Including Serious) Adverse Events
	Prophylactic Surfactant		Surfactant Extubated to nCPAP		NCPAP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/209 (0%)		0/216 (0%)		0/223 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.