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

NCT03530124 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: Pro00088094200 2012 53663 0010
• Study Type: interventional
• Target: 223
• Locations: 1 country
• Sites: 4

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.

Conditions

Apnea; Apnea Neonatal; Prematurity

Keywords

apnea following vaccination

Outcome Measures

Primary Outcomes (1)

• Occurrence of Apnea

  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 Outcomes (5)

• Number of Apneic Episodes

  48 hours

• Duration of Apneic Episodes

  48 hours

• Increase in Respiratory Support

  48 hours

• Severe Cardiorespiratory Events

  48 hours

• Positive Pressure Ventilation

  48 hours

Study Arms (2)

Vaccinated

OTHER

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.

Biological: PCV13; Biological: DTaP; Biological: HBV; Biological: IPV; Biological: Hib

Unvaccinated

NO INTERVENTION

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.

Interventions

PCV13 BIOLOGICAL

Advisory Committee on Immunization Practices (ACIP) Recommended vaccine

Also known as: 13-valent Conjugate Pneumococcal Vaccine

Vaccinated

DTaP BIOLOGICAL

ACIP Recommended vaccine

Also known as: Diphtheria, Tetanus, and Acellular Pertussis Vaccine

Vaccinated

HBV BIOLOGICAL

ACIP Recommended vaccine

Also known as: Hepatitis B Vaccine

Vaccinated

IPV BIOLOGICAL

ACIP Recommended vaccine

Also known as: Inactivated Polio Vaccine

Vaccinated

Hib BIOLOGICAL

ACIP Recommended vaccine

Also known as: Haemophilus influenzae Type B Vaccine

Vaccinated

Eligibility Criteria

• Age: 6 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \<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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Centers for Disease Control and Prevention: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of North Carolina: collaborator

Study Sites (4)

Centers for Disease Control and Prevention

Atlanta, Georgia, 30329, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• Greenberg RG, Rountree W, Staat MA, Schlaudecker EP, Poindexter B, Trembath A, Laughon M, Poniewierski MS, Spreng RL, Broder KR, Wodi AP, Museru O, Anyalechi EG, Marquez PL, Randolph EA, Aleem S, Kilpatrick R, Walter EB. Apnea After 2-Month Vaccinations in Hospitalized Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2025 Mar 1;179(3):246-254. doi: 10.1001/jamapediatrics.2024.5311.

  PMID: 39761016 DERIVED

MeSH Terms

Conditions

Apnea; Premature Birth

Interventions

Diphtheria-Tetanus-acellular Pertussis Vaccines; Hepatitis B Vaccines; Poliovirus Vaccine, Inactivated

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pertussis Vaccine; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined; Vaccines, Acellular; Vaccines, Subunit; Viral Hepatitis Vaccines; Viral Vaccines; Vaccines, Inactivated; Poliovirus Vaccines

Results Point of Contact

• Title: Dr. Rachel Greenberg
• Organization: Duke University

rachel.greenberg@duke.edu

919 668 4725

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2018
• First Posted: May 21, 2018
• Study Start: July 17, 2018
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: February 14, 2024
• Results First Posted: January 11, 2023

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)