PMID- 18827210 OWN - NLM STAT- MEDLINE DCOM- 20081007 LR - 20161017 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 300 IP - 13 DP - 2008 Oct 1 TI - Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial. PG - 1532-43 LID - 10.1001/jama.300.13.1532 [doi] AB - 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, AND PARTICIPANTS: 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 OUTCOME MEASURES: 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. FAU - Marano, Nina AU - Marano N AD - Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. FAU - Plikaytis, Brian D AU - Plikaytis BD FAU - Martin, Stacey W AU - Martin SW FAU - Rose, Charles AU - Rose C FAU - Semenova, Vera A AU - Semenova VA FAU - Martin, Sandra K AU - Martin SK FAU - Freeman, Alison E AU - Freeman AE FAU - Li, Han AU - Li H FAU - Mulligan, Mark J AU - Mulligan MJ FAU - Parker, Scott D AU - Parker SD FAU - Babcock, Janiine AU - Babcock J FAU - Keitel, Wendy AU - Keitel W FAU - El Sahly, Hana AU - El Sahly H FAU - Poland, Gregory A AU - Poland GA FAU - Jacobson, Robert M AU - Jacobson RM FAU - Keyserling, Harry L AU - Keyserling HL FAU - Soroka, Stephen D AU - Soroka SD FAU - Fox, Sarah P AU - Fox SP FAU - Stamper, John L AU - Stamper JL FAU - McNeil, Michael M AU - McNeil MM FAU - Perkins, Bradley A AU - Perkins BA FAU - Messonnier, Nancy AU - Messonnier N FAU - Quinn, Conrad P AU - Quinn CP CN - Anthrax Vaccine Research Program Working Group LA - eng SI - ClinicalTrials.gov/NCT00119067 PT - Clinical Trial, Phase IV PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Anthrax Vaccines) RN - 0 (Antibodies, Bacterial) RN - 0 (Immunoglobulin G) SB - IM EIN - JAMA. 2008 Nov 19;300(19):2252 MH - Adult MH - Anthrax Vaccines/*administration & dosage/adverse effects/*immunology MH - Antibodies, Bacterial/immunology MH - Bacillus anthracis/immunology MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Humans MH - Immunoglobulin G/immunology MH - Injections, Intramuscular MH - Injections, Subcutaneous MH - Male MH - Middle Aged FIR - Babcock, Janiine IR - Babcock J FIR - Gibbs, Barnett IR - Gibbs B FIR - Yoon, In-Kyu IR - Yoon IK FIR - Moon, James IR - Moon J FIR - Kester, Kent IR - Kester K FIR - Bond, Nanette IR - Bond N FIR - Tajonera, Celsa IR - Tajonera C FIR - Cornatzer, Kelly IR - Cornatzer K FIR - Bourgeois, Franchelle IR - Bourgeois F FIR - Henry, Chanei IR - Henry C FIR - Cicatelli, Susan IR - Cicatelli S FIR - Newcomer, Rhonda IR - Newcomer R FIR - Nielsen, Robin IR - Nielsen R FIR - Taylor-Means, Sheila IR - Taylor-Means S FIR - Anderson, Betty J IR - Anderson BJ FIR - Diskerud, Rebecca S IR - Diskerud RS FIR - Targonski, Paul V IR - Targonski PV FIR - Madsen, Charles D IR - Madsen CD FIR - Pinsky, Norman A IR - Pinsky NA FIR - Ryan, Jenna E IR - Ryan JE FIR - Hilinski, Joseph IR - Hilinski J FIR - Leonard, Michael Jr IR - Leonard M Jr FIR - Grimes, Vickie IR - Grimes V FIR - Luehrs, Karen IR - Luehrs K FIR - Newsome, Pamela IR - Newsome P FIR - Skvarich, Jane IR - Skvarich J FIR - Stephens, Kathleen IR - Stephens K FIR - Abramson, Darbi IR - Abramson D FIR - Brawner, Melissa IR - Brawner M FIR - Brown, Natasha IR - Brown N FIR - Desai, Rita IR - Desai R FIR - Mothershed, Elizabeth IR - Mothershed E FIR - Schiffer, Jarad IR - Schiffer J FIR - Schmidt, Daniel IR - Schmidt D FIR - Stamey, Karen IR - Stamey K FIR - Steward-Clark, Evelene IR - Steward-Clark E FIR - Walls, John IR - Walls J FIR - Ari, Mary IR - Ari M FIR - Chiang, I-Shan IR - Chiang IS FIR - Holt, Walter IR - Holt W FIR - Pathak, Sonal IR - Pathak S FIR - Seright, Antoinette IR - Seright A FIR - Wright, Jennifer G IR - Wright JG FIR - Asher, Jamie IR - Asher J FIR - Avery, Douglas IR - Avery D FIR - Caba, Joseph IR - Caba J FIR - Crenshaw, Shannon IR - Crenshaw S FIR - Cronin, Li IR - Cronin L FIR - Dababneh, Hanan IR - Dababneh H FIR - Davis, Lydia IR - Davis L FIR - Feagins, Alicia IR - Feagins A FIR - Gillis, Eric IR - Gillis E FIR - Lyde, Freda IR - Lyde F FIR - Mahle, Kristen IR - Mahle K FIR - Riley, Pamela IR - Riley P FIR - Smith, Darlyne IR - Smith D FIR - Thompson, Rhonda IR - Thompson R FIR - Stinson, Kelly Wallace IR - Stinson KW FIR - Ashford, David IR - Ashford D FIR - Carlone, George IR - Carlone G FIR - Lingappa, Jairam IR - Lingappa J FIR - Stokes, Susan IR - Stokes S FIR - Tappero, Jordan IR - Tappero J EDAT- 2008/10/02 09:00 MHDA- 2008/10/08 09:00 CRDT- 2008/10/02 09:00 PHST- 2008/10/02 09:00 [pubmed] PHST- 2008/10/08 09:00 [medline] PHST- 2008/10/02 09:00 [entrez] AID - 300/13/1532 [pii] AID - 10.1001/jama.300.13.1532 [doi] PST - ppublish SO - JAMA. 2008 Oct 1;300(13):1532-43. doi: 10.1001/jama.300.13.1532.