NCT00707148

Brief Summary

The purpose of this study is to look at the safety and immunogenicity of a combination vaccine that includes tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). The study will be conducted in 48 pregnant women and 32 non-pregnant women. Safety of the newborn infant and the effect of the mother's vaccination on the infants' immune responses prior to vaccinating infants with another combination vaccine to protect against diphtheria, tetanus, and pertussis will be evaluated. Participants will be 18-45 years old. Pregnant volunteers will be 30-32 weeks pregnant and at a low risk for pregnancy complications. Pregnant volunteers will receive 2 injections (1 vaccine and 1 placebo, inactive substance); non-pregnant volunteers will receive 1 injection of vaccine. Blood samples will be collected from the mother and infant, along with the baby's growth measurements. Participation for mother infant pairs is about 15 months and about 7 months for non-pregnant women.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
80

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2009

Typical duration for phase_1

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 26, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 30, 2008

Completed
6 months until next milestone

Study Start

First participant enrolled

January 1, 2009

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2012

Completed
Last Updated

July 25, 2014

Status Verified

August 1, 2012

Enrollment Period

3.3 years

First QC Date

June 26, 2008

Last Update Submit

July 24, 2014

Conditions

Keywords

pertussis, diptheria, tetanus, vaccine, Tdap

Outcome Measures

Primary Outcomes (6)

  • Incidence of injection site and systemic reactions following injections.

    Recorded 0 to 7 days after injection.

  • Frequency of vaccine-associated adverse events (AEs).

    30 minutes post-injection, Day 0, 1-2, 7, 4 weeks post-injection, delivery, Day 1-2, 7, and 2 and 4 months post-delivery. Infant AEs: Delivery, 2, 4, 7, and 13 months. Non-pregnant: Day 0, 1-2, 7, 4 weeks and 6 months.

  • Frequency of vaccine-associated serious adverse events (SAEs).

    Maternal SAEs through 4 months post delivery and infant SAEs from delivery to 13 months. Non-pregnant SAEs: Day 0 through to 6 months post-injection.

  • Infant growth measurements (fronto-occipital circumference [FOC], length and weight).

    At delivery and at 2, 7 and 13 months of age.

  • Bayley III developmental screening of infants.

    At age 13 months.

  • Incidence of pertussis infection captured by surveillance for adverse events (AEs) and serious adverse events (SAEs).

    Duration of study, captured by surveillance for AEs and SAEs. Antepartum: Day 1-2 and 7; 4 weeks; delivery. Postpartum: Day 1-2 and 7; Month 2, 4,7, and 13.

Secondary Outcomes (1)

  • Concentrations of immunoglobulin G (IgG) for pertussis toxin (PT), pertactin (PRN), fimbrial proteins (FIM), filamentous hemagglutinin (FHA), tetanus toxoid (TT), and diphtheria toxoid (DT).

    Mother: blood samples collected before and 4 weeks after antepartum injection, at hospital admission for delivery and at the 2 month post delivery visit. Infant: collected at delivery (cord), 2, 7 and 13 months of age.

Study Arms (3)

Group 2: Control

ACTIVE COMPARATOR

16 pregnant women to receive: antepartum: saline; postpartum; Tdap vaccine.

Drug: PlaceboBiological: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed

Group 1: Intervention

EXPERIMENTAL

32 pregnant women to receive: antepartum: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) vaccine; postpartum: saline.

Drug: PlaceboBiological: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed

Group 3: Control

ACTIVE COMPARATOR

32 non-pregnant women to receive a single dose of Tdap vaccine.

Biological: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed

Interventions

Saline (0.9% NaCl) administered as a single 0.5 mL intramuscular injection into the deltoid.

Group 1: InterventionGroup 2: Control

Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine absorbed (Tdap). Administered as a single 0.5 mL intramuscular injection into the deltoid.

Group 1: InterventionGroup 2: ControlGroup 3: Control

Eligibility Criteria

AgeUp to 45 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • years of age
  • In the 30th-32nd week of a pregnancy at low risk for complications as determined by the Obstetrical Risk Assessment Form \[ORAF\] and the following criteria:
  • All Pregnant Women:
  • Second trimester or later ultrasound with no significant abnormalities.
  • Alpha fetal protein (AFP) testing, one of the following:
  • Normal maternal serum AFP performed at 15-20 weeks' gestation (either as part of the quad screen or separately)
  • Abnormal maternal serum AFP at 15-20 weeks' gestation followed by an amniocentesis demonstrating no chromosomal abnormalities AND either normal amniotic fluid AFP or normal amniotic fluid acetylcholinesterase (AChE) levels.
  • If a serum AFP test is not performed, one of the following:
  • i. A level II ultrasound with no significant abnormalities ii. A normal amniotic fluid AFP test AND an amniocentesis demonstrating no chromosomal abnormalities must be documented.
  • Pregnant Women 40-45 years of age: no chromosomal abnormalities identified by diagnostic testing \[chorionic villus sampling (CVS) or amniocentesis\].
  • Pregnant Women 18-39 years of age: at least one of the following:
  • Level II ultrasound with no significant abnormalities
  • No chromosomal abnormalities identified by diagnostic testing (CVS or amniocentesis)
  • Pregnancy estimated to be at low risk (\< 1 in 270) for Down's syndrome (trisomy 21), trisomy 13 and trisomy 18 by appropriate first or second trimester screening test. Appropriate screening test includes any one of the following:
  • i. first trimester screening (nuchal translucency measurement, pregnancy-associated plasma protein A (PAPP-A), and beta- human chorionic gonadotropin (B-hCG) ii. first trimester screening and second trimester quad screen, with risk estimated using an integrated, sequential, or contingency approach iii. second trimester quad screen alone
  • +8 more criteria

You may not qualify if:

  • Serious underlying medical condition (e.g., immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection, collagen vascular disease, diabetes mellitus, chronic hypertension, moderate to severe asthma, lung/heart disease, liver/kidney disease, chronic or recurrent infections).
  • Significant mental illness (e.g. schizophrenia, psychosis, major depression).
  • Currently smoking or using illegal substances.
  • History of a febrile illness (greater than or equal to 100.4 degrees Fahrenheit or 38 degrees Celsius) within the past 72 hours for antepartum injection or febrile illness (greater than or equal to 100.4 degrees Fahrenheit or 38 degrees Celsius) within 24 hours for postpartum injection.
  • Previous severe reaction to any vaccine.
  • Receipt of tetanus-diphtheria toxoid immunization within the past 2 years.
  • Receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine absorbed (Tdap) immunization ever.
  • Receipt of a vaccine (excluding influenza), blood product (excluding Rhogam) or experimental medicine within the 4 weeks prior to antepartum injection through 4 weeks following post-partum injection. However, measles-mumps-rubella vaccine is permitted post-partum.
  • Receipt of or plans to receive influenza vaccine within the 2 weeks prior to or following antepartum injection.
  • Deemed high risk for serious obstetrical complication as determined by the Obstetrical Risk Assessment Form.
  • Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk.
  • Serious underlying medical condition (e.g., immunosuppressive disease or therapy, HIV infection, collagen vascular disease, diabetes mellitus, chronic hypertension, moderate to severe asthma, lung/heart disease, liver/kidney disease, chronic or recurrent infections).
  • Significant mental illness (e.g. schizophrenia, psychosis, major depression).
  • Currently smoking or using illegal substances.
  • History of a febrile illness (greater than or equal to 100.4 degrees Fahrenheit or 38 degrees Celsius) within the past 24 hours.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Duke University Medical Center - Duke Perinatal Clinic

Durham, North Carolina, 27705, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

Group Health Research Institute - Seattle

Seattle, Washington, 98101-1466, United States

Location

Seattle Children's Hospital - Infectious Diseases

Seattle, Washington, 98105-3901, United States

Location

Related Publications (1)

  • Munoz FM, Bond NH, Maccato M, Pinell P, Hammill HA, Swamy GK, Walter EB, Jackson LA, Englund JA, Edwards MS, Healy CM, Petrie CR, Ferreira J, Goll JB, Baker CJ. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial. JAMA. 2014 May 7;311(17):1760-9. doi: 10.1001/jama.2014.3633.

MeSH Terms

Conditions

DiphtheriaWhooping CoughTetanus

Interventions

Tetanus Toxoid

Condition Hierarchy (Ancestors)

Corynebacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsBordetella InfectionsGram-Negative Bacterial InfectionsRespiratory Tract InfectionsRespiratory Tract DiseasesClostridium Infections

Intervention Hierarchy (Ancestors)

ToxoidsVaccinesBiological ProductsComplex Mixtures

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
CROSSOVER
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 26, 2008

First Posted

June 30, 2008

Study Start

January 1, 2009

Primary Completion

May 1, 2012

Study Completion

May 1, 2012

Last Updated

July 25, 2014

Record last verified: 2012-08

Locations