Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults: new considerations for the management of patients with tetanus-prone injuries

Abstract

In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5-10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28.

Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: -1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed.

Trial registration: ClinicalTrials.gov NCT00928785.

Keywords: REPEVAX®; Tdap-IPV vaccine; immunogenicity; injuries; safety; tetanus toxoid.

Figures

Figure 1. Flow of participants through the study. %, percentage based on the number of randomized participants: aFull analysis population: all randomized participants who received one of the study vaccines and with a post-vaccination immunogenicity evaluation. Participants were analyzed in the group to which they were randomized. bSafety analysis population: all participants who received one of the study vaccines and who had safety follow-up data. Participants were analyzed according to the study vaccine they actually received. In the Tdap-IPV group, one participant was lost to follow up and in the Tetanus monovalent group, one participant withdrew consent. Both withdrew before Day 10. cDay 10, per protocol population: all randomized participants excluding those with protocol violation(s) that may have interfered with the immunogenicity evaluation at Day 10. In both groups, 56 participants (12.3%) did not meet the inclusion criteria/met the exclusion criteria, 38 of them having received more than 1 tetanus-containing vaccine 5–10 y prior to study vaccine. In both groups, protocol violations were: at day 10, no post-vaccination immunogenicity data (n = 2); post-vaccination blood sampling out of day range (n = 3). dDay 28, per protocol population: all randomized participants excluding those with protocol violation(s) that may have interfered with the immunogenicity evaluation post-vaccination at Day 28. In both groups, these protocol violations consisted of: at Day 28, no post-vaccination immunogenicity data (n = 4); post-vaccination blood sampling out of day range (n = 9); received a non-study vaccine (n = 6).

Figure 2. Reverse cumulative distribution of anti-tetanus concentration (IU/mL – ELISA), at day 10 (per protocol population).