Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial.
JAMA
; 300(13): 1532-43, 2008 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-18827210
ABSTRACT
CONTEXT In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA). OBJECTIVE:
To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule. DESIGN, SETTING, ANDPARTICIPANTS:
Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002). INTERVENTION Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals. MAIN OUTCOMEMEASURES:
Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.RESULTS:
At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.CONCLUSIONS:
The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier NCT00119067.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anthrax Vaccines
Type of study:
Clinical_trials
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
JAMA
Year:
2008
Document type:
Article
Affiliation country:
United States