Apnea in Hospitalized Preterm Infants Following the Administration of Routine Childhood Vaccines
A Prospective, Randomized, Open-label Clinical Trial to Assess Apnea Following Administration of 13-valent Conjugate Pneumococcal Vaccine, Diphtheria Toxoid, Tetanus Toxoid, and Acellular Pertussis Vaccine, Inactivated Polio Vaccine, Hepatitis B Vaccine, and Haemophilus Influenzae Type B Vaccine in Preterm Infants
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Modified Intent-to-Treat (mITT) Analysis Population: Defined as any infant that was enrolled and randomized in the study
For the mITT analysis, infants will be analyzed in their assigned treatment arms irrespective of receipt of vaccine. Study outcomes will be included in the analysis as follows:
i) Vaccinated group: study outcomes in the 48-hour monitoring after vaccination. If vaccination does not occur by 12 hours after randomization, then study outcomes will be assessed between 12 and 60 hours after randomization.
ii) Unvaccinated group: study outcomes in the 48-hour monitoring period after randomization.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30329
- Centers for Disease Control and Prevention
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- University of North Carolina
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Durham, North Carolina, United States, 27705
- Duke University
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Ohio
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- <33 and 0 days weeks gestational age at birth
- ≥6 weeks and 0 days and ≤12 weeks and 0 days postnatal age at randomization
- Remains hospitalized after birth (has never been discharged home)
- Treating clinician deems infant eligible to receive 2-month vaccines
- English- or Spanish-speaking parent(s)/legally authorized representative(s) (LAR(s))
- Not planned for discharge within 60 hours of study entry
- The parent/guardian must be willing and capable of providing permission for their child to participate through the written informed consent process
Exclusion Criteria:
- Receipt of DTaP, IPV, PCV13, or Hib prior to enrollment. Previous administration of the first dose of HBV is permitted
- Anticipated receipt of any vaccine other than DTaP, IPV, HBV, PCV13, or Hib during the first 60 hours after randomization
- History of a severe allergic reaction (e.g. anaphylaxis) to a previous dose of any hepatitis B vaccine
- History of a severe allergic reaction (e.g. anaphylaxis) to any component of the vaccines used in the study including neomycin, yeast and polymyxin B
- History of latex allergy
Fever ≥38°C within 48 hours prior to randomization*
*This may result in a temporary delay of randomization
Active known respiratory infection within 48 hours prior to randomization*
*This may result in a temporary delay of randomization
Active infection being treated with systemic antimicrobials*
*This may result in a temporary delay of randomization
Requiring mechanical ventilation or support with nasal intermittent positive pressure ventilation (NIPPV)*
*This may result in a temporary delay of randomization
- History of unstable progressive neurologic disorder of unknown cause
- Known cause of apnea other than apnea of prematurity
- Cyanotic heart disease (congenital or acquired)
Major invasive medical or surgical procedure (including circumcision) within 48 hours prior to randomization or anticipated to have major invasive medical or surgical procedure during the first 60 hours after randomization*
*This may result in a temporary delay of randomization
- Child or parent/LAR is an immediate relative of study staff or an employee who is supervised by study staff.
- Any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: Vaccinated
In the study arm, infants will receive PCV13, DTaP, HBV, IPV, and Hib vaccines within 12 hours of randomization.
Infants will be monitored from time of vaccination to 48 hours post-vaccination for the occurrence of apnea, bradycardia and desaturation.
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Advisory Committee on Immunization Practices (ACIP) Recommended vaccine
Other Names:
ACIP Recommended vaccine
Other Names:
ACIP Recommended vaccine
Other Names:
ACIP Recommended vaccine
Other Names:
ACIP Recommended vaccine
Other Names:
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No Intervention: Unvaccinated
In the study arm, infants will not receive PCV13, DTaP, HBV, IPV, and Hib vaccines during the study.
Infants will be monitored from randomization to 48 hours post-randomization for the occurrence of apnea, bradycardia and desaturation.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Occurrence of Apnea
Time Frame: 48 hours
|
Number of infants with ≥ 1 apneic event in a 48-hour monitoring period after vaccination in the "vaccinated" group and a 48-hour monitoring period after randomization in the "unvaccinated" group, mITT Population Apnea was defined as a pause in respirations of >20 seconds, or a pause in respirations of >15 seconds with associated bradycardia (heart rate <80 beats per minute for any duration occurring within 1 minute of the apnea event). Potential apnea events triggered by the cardiorespiratory monitors were manually reviewed by 2 neonatologists to verify the event. In uncommon situations in which manual review of a triggered event was not possible due to missing data, the triggered event was considered to be apnea. |
48 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of Apneic Episodes
Time Frame: 48 hours
|
Average number of apneic episodes in a 48-hour monitoring period after vaccination in the "vaccinated" group and a 48-hour monitoring period after randomization in the "unvaccinated" group.
|
48 hours
|
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Duration of Apneic Episodes
Time Frame: 48 hours
|
Average duration of apneic episodes in a 48-hour monitoring period after vaccination in the "vaccinated" group and a 48-hour monitoring period after randomization in the "unvaccinated" group.
|
48 hours
|
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Increase in Respiratory Support
Time Frame: 48 hours
|
Proportion of infants requiring any increase in respiratory support in a 48-hour monitoring period after vaccination in the "vaccinated" group and a 48-hour monitoring period after randomization in the "unvaccinated" group.
|
48 hours
|
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Severe Cardiorespiratory Events
Time Frame: 48 hours
|
Proportion of infants with severe ≥1 severe cardiorespiratory event in a 48-hour monitoring period after vaccination in the "vaccinated" group and a 48-hour monitoring period after randomization in the "unvaccinated" group. Only severe apnea events in the mITT analysis window and only the severe bradycardia events in the mITT analysis window from Duke University. The monitor data were not viable at UNC and Cincinnati Children's Hospital. Duke data were adjudicated by neonatologists. |
48 hours
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Positive Pressure Ventilation
Time Frame: 48 hours
|
Proportion of Infants Requiring Positive Pressure Ventilation in a 48-hour monitoring period after vaccination in the "vaccinated" group and a 48-hour monitoring period after randomization in the "unvaccinated" group.
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48 hours
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Rachel G Greenberg, MD, Duke University
- Principal Investigator: Andrea Trembath, MD, University of North Carolina
- Principal Investigator: Mary A Staat, MD, Children's Hospital Medical Center, Cincinnati
- Principal Investigator: Karen Broder, MD, Centers for Disease Control and Prevention
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00088094
- 200 2012 53663 0010 (Other Grant/Funding Number: CDC)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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