Apnea in Hospitalized Preterm Infants Following the Administration of Routine Childhood Vaccines

• ClinicalTrials.gov Identifier: NCT03530124
• Recruitment Status: Completed
• First Posted: May 21, 2018
• Last Update Posted: December 14, 2021
• Sponsor: Duke University
• Collaborators: Centers for Disease Control and Prevention; Children's Hospital Medical Center, Cincinnati; University of North Carolina
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

A prospective, randomized open-label clinical trial will be conducted from July 2018 to October 2020. Approximately 300 preterm infants will be enrolled across three sites: Duke University Medical Center, the University of North Carolina, and Cincinnati Children's Hospital Medical Center. Eligible infants will be randomized 1:1 to receive either 2-month US licensed childhood vaccines (PCV13, DTaP, HBV, IPV an Hib) or no vaccines. After their participation in the study, healthcare providers of the infants in the unvaccinated group will make decision abut receipt of their 2-month childhood vaccines. The study will collect data from the continuous cardiorespiratory and pulse oximetry monitors from randomization to 48 hours after randomization for infants in the unvaccinated group, and from randomization to 48 hours after vaccination for infants in the vaccinated group. Infants in both groups will be monitored for up to 60 hours for the occurrence of apnea, bradycardia, and oxygen desaturation. For infants in the "vaccinated" group, the study will also collect adverse events of clinical interest and serious adverse events occurring between the end of the 48-hour monitoring period and 14 days after vaccination. This information will be collected through parental report and review of medical records.

Condition or disease	Intervention/treatment	Phase
Apnea; Apnea Neonatal; Prematurity	Biological: PCV13; Biological: DTaP; Biological: HBV; Biological: IPV; Biological: Hib	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Apnea in Hospitalized Preterm Infants Following the Administration of Routine Childhood Vaccines
• Actual Study Start Date: July 17, 2018
• Actual Primary Completion Date: November 1, 2021
• Actual Study Completion Date: November 1, 2021

Arms and Interventions

Arm	Intervention/treatment
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 randomization to 48 hours post-vaccination for the occurrence of apnea, bradycardia and desaturation.	Biological: PCV13; ACIP Recommended vaccine; Other Name: 13-valent Conjugate Pneumococcal Vaccine; Biological: DTaP; ACIP Recommended vaccine; Other Name: Diphtheria, Tetanus, and Acellular Pertussis Vaccine; Biological: HBV; ACIP Recommended vaccine; Other Name: Hepatitis B Vaccine; Biological: IPV; ACIP Recommended vaccine; Other Name: Inactivated Polio Vaccine; Biological: Hib; ACIP Recommended vaccine; Other Name: Haemophilus influenzae Type B Vaccine
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.

Outcome Measures

Primary Outcome Measures :

1. Occurrence of Apnea [ Time Frame: Up to 60 hours post-randomization ]
   Proportion 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.

Secondary Outcome Measures :

1. Number of Apneic Episodes [ Time Frame: Up to 60 hours post-randomization ]
   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.
2. Duration of Apneic Episodes [ Time Frame: Up to 60 hours post-randomization ]
   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.
3. Increase in Respiratory Support [ Time Frame: Up to 60 hours post-randomization ]
   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.
4. Severe Cardiorespiratory Events [ Time Frame: Up to 60 hours post-randomization ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 6 Weeks and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. ≤32 weeks gestational age at birth
2. ≥6 weeks postnatal age at randomization
3. Remains hospitalized after birth (has never been discharged home)
4. Treating clinician deems infant eligible to receive 2-month vaccines
5. English- or Spanish-speaking parent(s)/legally authorized representative(s) (LAR(s))
6. Not planned for discharge within 60 hours of study entry
7. The parent/guardian must be willing and capable of providing permission for their child to participate through the written informed consent process

Exclusion Criteria:

1. Receipt of DTaP, IPV, PCV13, or Hib prior to enrollment. Previous administration of the first dose of HBV is permitted
2. Anticipated receipt of any vaccine other than DTaP, IPV, HBV, PCV13, or Hib during the first 60 hours after randomization
3. History of a severe allergic reaction (e.g. anaphylaxis) to a previous dose of any hepatitis B vaccine
4. 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
5. History of latex allergy

6. Fever ≥38°C within 48 hours prior to randomization*

   *This may result in a temporary delay of randomization

7. Active known respiratory infection within 48 hours prior to randomization*

   *This may result in a temporary delay of randomization

8. Active infection being treated with systemic antimicrobials*

   *This may result in a temporary delay of randomization

9. Requiring mechanical ventilation or support with nasal intermittent positive pressure ventilation (NIPPV)*

   *This may result in a temporary delay of randomization

10. History of unstable progressive neurologic disorder of unknown cause
11. Known cause of apnea other than apnea of prematurity
12. Cyanotic heart disease (congenital or acquired)

13. 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

14. Child or parent/LAR is an immediate relative of study staff or an employee who is supervised by study staff.
15. 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

Contacts and Locations

Locations

United States, Georgia

Centers for Disease Control and Prevention

Atlanta, Georgia, United States, 30333

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Duke University

Durham, North Carolina, United States, 27705

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

Duke University

Centers for Disease Control and Prevention

Children's Hospital Medical Center, Cincinnati

University of North Carolina

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: Patricia Wodi, MD; Centers for Disease Control and Prevention

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03530124
• Other Study ID Numbers: Pro00088094; 200 2012 53663 0010 ( Other Grant/Funding Number: CDC )
• First Posted: May 21, 2018
• Last Update Posted: December 14, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Duke University:

apnea following vaccination

Additional relevant MeSH terms:

Apnea; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs