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| ID | Type | Description | Link |
|---|---|---|---|
| 200 2012 53663 0010 | Other Grant/Funding Number | CDC |
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| Name | Class |
|---|---|
| Centers for Disease Control and Prevention | FED |
| Children's Hospital Medical Center, Cincinnati | OTHER |
| University of North Carolina | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PCV13 | Biological | Advisory Committee on Immunization Practices (ACIP) Recommended vaccine |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Apneic Episodes | 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 |
| Duration of Apneic Episodes |
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Inclusion Criteria:
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
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centers for Disease Control and Prevention | Atlanta | Georgia | 30329 | United States | ||
| University of North Carolina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39761016 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine HBV: ACIP Recommended vaccine IPV: ACIP Recommended vaccine Hib: ACIP Recommended vaccine |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine HBV: ACIP Recommended vaccine IPV: ACIP Recommended vaccine Hib: ACIP Recommended vaccine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The mITT population includes any infant that was enrolled and randomized in the study. | Posted | Count of Participants | Participants | 48 hours |
|
Unvaccinated infants and vaccinated infants were followed for 48 hours for clinically important adverse events and serious adverse events. In addition, vaccinated infants were followed for 14 days after vaccination for clinically important adverse events and serious adverse events.
All clinically important adverse events (not including serious adverse event) outcome data were reported out within the study outcome measures.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. PCV13: ACIP Recommended vaccine DTaP: ACIP Recommended vaccine HBV: ACIP Recommended vaccine IPV: ACIP Recommended vaccine Hib: ACIP Recommended vaccine |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospital readmission for tachypnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe Cardiorespiratory Event | Cardiac disorders | Systematic Assessment | Severe cardiorespiratory events were defined according to the protocol. Definition: Respiratory pause of >30 seconds in duration or bradycardia of <60 beats per minute for >10 seconds Duke Site Only - See Secondary Outcome #5 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rachel Greenberg | Duke University | 919 668 4725 | rachel.greenberg@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 22, 2024 | Jan 30, 2024 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 14, 2022 | Oct 20, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001049 | Apnea |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D022681 | Diphtheria-Tetanus-acellular Pertussis Vaccines |
| D017325 | Hepatitis B Vaccines |
| D011054 | Poliovirus Vaccine, Inactivated |
| ID | Term |
|---|---|
| D010567 | Pertussis Vaccine |
| D001428 | Bacterial Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
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| DTaP | Biological | ACIP Recommended vaccine |
|
|
| HBV | Biological | ACIP Recommended vaccine |
|
|
| IPV | Biological | ACIP Recommended vaccine |
|
|
| Hib | Biological | ACIP Recommended vaccine |
|
|
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 |
| Increase in Respiratory Support | 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 |
| Severe Cardiorespiratory Events | 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 |
| Positive Pressure Ventilation | 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. | 48 hours |
| Chapel Hill |
| North Carolina |
| 27599 |
| United States |
| Duke University | Durham | North Carolina | 27705 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Discharged prior to study completion |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Gestational Age in Weeks |
|
| Age, Customized | Gestational Age in Weeks | Count of Participants | Participants |
|
| Age, Customized | Postmenstrual age is defined as the sum of gestational age plus postnatal age | Median | Full Range | Postmenstrual Age in Weeks |
|
| Age, Customized | Median | Full Range | Postnatal Age in Weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Multiple Gestation | Count of Participants | Participants |
|
| Birth Weight | Median | Full Range | Grams |
|
| Insurance | Count of Participants | Participants |
|
| Reason for Preterm Delivery | Count of Participants | Participants |
|
| Received Synagis During Study Period | Count of Participants | Participants |
|
| Received Caffeine | Data not collected on 6 participants. | Count of Participants | Participants |
|
| Sibling Enrolled in Study | Count of Participants | Participants |
|
| Respiratory Support at Randomization | Data not collected on 1 participant. | Count of Participants | Participants |
|
| Combination Vaccine Brand Administered | Pediarix contains DTap-IPV-HBV; Pentacel contains DTaP-IPV-Hib | Collection of combination vaccine data were collected for the vaccinated arm only. Data not collected on 5 participants. | Count of Participants | Participants |
|
| Haemophilus influenzae type b Vaccine Brand Administered | Collection of Haemophilus influenzae type b vaccine data were collected for the vaccinated arm only. Data not collected on 7 participants. | Count of Participants | Participants |
|
| Hepatitis B Vaccine Brand Administered - Engerix-B | Engerix-B is the only Hepatitis B vaccine reported during study period | Collection of Hepatitis B vaccine data were collected for the vaccinated arm only. | Count of Participants | Participants |
|
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.
PCV13: ACIP Recommended vaccine
DTaP: ACIP Recommended vaccine
HBV: ACIP Recommended vaccine
IPV: ACIP Recommended vaccine
Hib: ACIP Recommended vaccine
| OG001 | 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. |
|
|
|
| Secondary | Number of Apneic Episodes | 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. | The mITT population includes any infant that was enrolled and randomized in the study. | Posted | Mean | Standard Deviation | Apneic Episodes | 48 hours |
|
|
|
|
| Secondary | Duration of Apneic Episodes | 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. | The mITT population includes any infant that was enrolled and randomized in the study. | Posted | Mean | Standard Deviation | seconds | 48 hours |
|
|
|
|
| Secondary | Increase in Respiratory Support | 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. | The mITT population includes any infant that was enrolled and randomized in the study. | Posted | Count of Participants | Participants | 48 hours |
|
|
|
|
| Secondary | Severe Cardiorespiratory Events | 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. | mITT Analysis Population: Duke Site Only | Posted | Count of Participants | Participants | 48 hours |
|
|
|
|
| Secondary | Positive Pressure Ventilation | 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. | The mITT population includes any infant that was enrolled and randomized in the study. | Posted | Count of Participants | Participants | 48 hours |
|
|
|
|
| 0 |
| 107 |
| 1 |
| 107 |
| 32 |
| 107 |
| EG001 | 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. | 0 | 116 | 0 | 116 | 20 | 116 |
| Hospital readmission for retinopathy of prematurity | Eye disorders | Systematic Assessment |
|
| Respiratory decompensation and hypotension following elective surgery | Surgical and medical procedures | Systematic Assessment |
|
|
| ≥ 1 Apneic Event | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Apneic events were defined according to the protocol. Definition: A pause in respirations of >20 seconds, or a pause in respirations of >15 seconds with associated bradycardia (heart rate <80 beats per minute) -See Primary Outcome #1 |
|
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D045424 |
| Complex Mixtures |
| D004168 | Diphtheria Toxoid |
| D014121 | Toxoids |
| D013745 | Tetanus Toxoid |
| D017778 | Vaccines, Combined |
| D022282 | Vaccines, Acellular |
| D022223 | Vaccines, Subunit |
| D014761 | Viral Hepatitis Vaccines |
| D014765 | Viral Vaccines |
| D015164 | Vaccines, Inactivated |
| D023321 | Poliovirus Vaccines |
| Unknown or Not Reported |
|
| Triplets |
|
| None |
|
| Missing |
|
| Missing |
|
| Missing |
|