Tdap and RSV vaccines in pregnancy: same visit versus separate visits

Concurrent Versus Sequential Administration of Tdap and RSV Vaccines in Pregnancy - A Pilot Feasibility Trial

This project will see if giving the RSV and Tdap vaccines together at one prenatal visit or at separate visits is safe and protects pregnant people and their babies better.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 49 Years
• Sex: Female
• Sponsor: Canadian Immunization Research Network (Research network)
• Locations: 4 sites (Vancouver, British Columbia and 3 other locations)
• Trial ID: NCT07097012 on ClinicalTrials.gov

What this trial studies

This Phase 4 interventional trial enrolls healthy pregnant participants and randomizes them to receive the RSV vaccine and Tdap either at the same visit or at separate visits, with saline used as a timing/placebo control when needed. Investigators will monitor safety events, collect blood to measure immune (antibody) responses in mothers, and follow infant outcomes. Optional follow-up includes measuring maternal antibody levels at about 7 and 19 months after delivery to understand longer-term responses. The trial is conducted at multiple Canadian vaccine research centers in Vancouver, Halifax and Ottawa.

Who should consider this trial

Good fit: Healthy pregnant people aged 18–49 with a singleton pregnancy at about 28 to 29+6 weeks gestation who have not recently received RSV vaccine or a recent pertussis vaccine are the intended participants.

Not a fit: People who previously received an RSV vaccine, had a pertussis vaccine within the prior two years, received immunoglobulins (other than Rho D) within a year, or who cannot attend the required visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could simplify prenatal vaccination scheduling and increase protection of infants and mothers against RSV and pertussis.

How similar studies have performed: Maternal Tdap and influenza vaccines have been safely coadministered in many studies, and recent standalone maternal RSV vaccine trials have shown promising immune and clinical results, but data specifically on coadministration of RSV with Tdap are limited.

Eligibility criteria

Inclusion Criteria

1. Healthy pregnant individuals with a singleton pregnancy aged 18-49 years.
2. Gestational age 28-29+6 WG at time of study screening, enrolment and randomization as per documented first trimester (less than or equal to13+6 WG) ultrasound, or the first date of last menstrual period if ultrasound not obtained in the first trimester, or the age of the embryo and the date of transfer if pregnancy resulted from assisted reproductive technology.
3. Able to comply with the study procedures required to achieve primary objective of this pilot trial (not being able to comply with procedures required to achieve exploratory objectives is not an exclusion criteria).
4. Informed consent read, understood and signed prior to study-specific procedures.

Exclusion Criteria

Any of the following:

1. Receipt of RSV vaccine anytime.
2. Receipt of immunoglobulins (except Rho D) within 1 year prior to vaccination.
3. Documented receipt of pertussis vaccine within 2 years prior to vaccination.
4. Documented pertussis infection (by culture or polymerase chain reaction) within 2 years prior to vaccination.
5. Receipt of blood transfusion products within 6 months prior to vaccination.
6. Primary or secondary immunologic disorder or immunosuppression.
7. Any conditions that, in the investigator's judgement, may interfere with subject's ability to comply with study procedures or receipt of prenatal care, such as behavioural or cognitive impairment or neuropsychiatric illness.
8. Preconception diabetes mellitus (defined as: previous diagnosis of diabetes while not pregnant OR First trimester hemoglobin A1c level of 6.5% \[47.5 mmol/mol\] OR First trimester fasting blood glucose 126 mg/dL \[7 mmol/L\]).
9. Preconception chronic hypertension (defined as: sustained elevation in the systolic blood pressure to ≥140 mmHg or the diastolic blood pressure to ≥90 mmHg, that is diagnosed either prior to pregnancy or prior to 20 WG).
10. Congenital anomalies per ultrasound.
11. Hepatitis B infection; Hepatitis C infection; Untreated syphilis.
12. Contraindication to receipt of Tdap (BOOSTRIX, GSK): a) Hypersensitivity to any component of the Tdap (BOOSTRIX, GSK) vaccine or individuals having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, or pertussis vaccines; b) Encephalopathy of unknown etiology, occurring within 7 days following previous vaccination with pertussis containing vaccine; c) Transient thrombocytopenia or neurological complications following an earlier immunization against diphtheria and/or tetanus.
13. Contraindication to receipt of RSVpreF (ABRYSVOTM, Pfizer): Hypersensitivity to the active substance or to any component of the vaccine.
14. Pregnancy complications at the time of recruitment that are risk factors for preterm delivery:

    1. Gestational hypertension (defined as new onset hypertension after 20 WG of systolic blood pressure is ≥140 mmHg or the diastolic blood pressure is ≥90 mmHg on two measurements at a minimum of one hour apart);
    2. Pre-eclampsia (defined as development of gestational hypertension \[as defined in #a above\] and proteinuria after 20 WG (Proteinuria defined as ≥300 mg in a 24 h urine specimen, or ≥0.30 on a spot protein: creatinine ratio, or ≥1+ on a dipstick;
    3. Gestational diabetes mellitus uncontrolled at time of consent (gestational diabetes is defined as a clinical syndrome characterized by the absence of preconception diabetes mellitus \[as defined in #8 above\] AND identification of sustained hyperglycemia during pregnancy not due to other known causes (i.e. corticosteroids, beta-mimetics, etc.) based on positive internationally recognized oral glucose tolerance test OR fasting plasma glucose of 92-125 mg/dL \[5.1-6.9 mmol/l\] using venous or capillary blood samples;
    4. Fetal growth restriction (defined as estimated fetal weight below 10% using locally-accepted growth curve AND Absent or reversed end-diastolic flow of the umbilical artery Doppler OR Oligohydramnios \[defined as a decreased amniotic fluid volume as defined by amniotic fluid index less than 8 cm or deepest vertical pocket less than 2 cm in the presence of intact membranes without concern for fetal anomalies contributing to its etiology\]);
    5. Placenta anomalies (placenta previa and abruptio, vasa previa);
    6. Polyhydramnios (defined as abnormal increase in the volume of amniotic fluid as either a deepest vertical pocket of ≥8 cm or an amniotic fluid index of ≥24 cm);
    7. Oligohydramnios (decreased amniotic fluid volume as defined in d above);
    8. Short uterine cervix (\<25 mm in the second trimester of pregnancy);
    9. A significant acute disease or oral temperature ≥38 Co within 24 hours prior to vaccination. Participants can return for evaluation to be randomized/vaccinated 72 hours after symptoms resolve, if they are still within 28-29+6 WG.

Where this trial is running

Vancouver, British Columbia and 3 other locations

• Vaccine Evaluation Center — Vancouver, British Columbia, Canada (Recruiting)
• Canadian Center for Vaccinology — Halifax, Nova Scotia, Canada (Recruiting)
• The Ottawa Hospital Research Institute — Ottawa, Ontario, Canada (Recruiting)
• Centre hospitalier universitaire Ste-Justine — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Bahaa Abu-Raya, M.D., PhD — Canadian Center for Vaccinology, Dalhousie University
• Study coordinator: Bahaa Abu-Raya, M.D, PhD

Conditions RSV; Tdap - Tetanus, Diphtheria and Acellular Pertussis Vaccination; Pregnancy; Healthy; Tdap; Clinical trial; Vaccine