1. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection
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Wilcox, M. H., Gerding, D. N., Poxton, I. R., Kelly, C., Nathan, R., Birch, T., Cornely, O. A., Rahav, G., Bouza, E., Lee, C., Jenkin, G., Jensen, W., Kim, Y. -S., Yoshida, J., Gabryelski, L., Pedley, A., Eves, K., Tipping, R., Guris, D., Kartsonis, N., Playford G, Dorr M. -B., Mcgechie, D, Iredell, J, Allworth, A, Cheng, A, Choi, Nj, Thalhammer, F, Maieron, A, Wenisch, C, Meyer, B, Jacobs, F, Delmee, M, Peetermans, W, Giot, Jb, Munhoz, Al, Kallas, Eg, Ladeira, Jp, Bernstein, Cn, Grimard, D, Mcgeer, A, Poirier, A, Valiquette, L, Miller, M, Oughton, M, Trottier, S, Dolce, P, Smyth, D, Gambra, P, Palma, S, Rojas, L, Northland, R, Arellano, Mc, Perez, J, Barreto, Mf, Gomez, Jm, Ramirez, I, Correa, A, Onate, J, Rohacova, H, Stastnik, M, Zjevikova, A, Blazek, J, Kumpel, P, Petersen, Am, Gluud, Ll, Staugaard, Hm, Tvede, M, Glerup, H, Madsen, Sm, Helms, M, Naumann, R, Karthaus, M, Reinshagen, M, Raz, R, Giladi, M, Chowers, M, Bishara, J, Quirino, T, Castelli, F, Bassetti, M, Rizzardini, G, Vismara, E, Puoti, M, Viale, P, Menichetti, F, Cauda, R, Bonfanti, P, Franzetti, F, Gori, A, Minoli, L, Noriega, Er, Mills, Gd, Ritchie, S, Burns, A, Pithie, A, dos Santos RM, Aldomiro, F, Fernando, Pb, Rola, J, Reis, E, Van Zyl JH, Aboo, N, Richards, G, Hernandez, Mj, de Medrano VA, Prunonosa, Lm, Gonzalez, Jl, Reinoso, Jc, Martinez, Ar, Cisneros, Jd, Banos, Jr, Sheridan, R, Minton, J, Williams, J, Stanley, P, Guleri, A, Llewelyn, M, Todd, N, Barlow, G, Bacon, Ae, Baird, Im, Baxter, R, Zenilman, Jm, Beshay, M, Betts, Rf, Brettholz, Em, Buitrago, Mi, Carlson, Rw, Cook, Pp, Dupont, Hl, Foley, C, Freilich, B, Giron, Ja, Golan, Y, Green, S, Hall, Mc, Johnson, Dj, Jones, Rk, Graham, Dr, Kazimir, M, Keating, M, Brumble, Lm, Kumar, Pn, Liappis, Ap, Libke, R, Mehra, Pk, Overcash, Sj, Mullane, Km, Nguyen, Mh, Patel, Mc, Powers, Ck, Pullman, J, Keegan, J, Nepal, S, English, G, Ricci, Rl, Risi, Gf, Rodriguez, M, Schmitt, Cm, Sims, Md, Kamepalli, R, Tural, A, Vazquez, Ja, Alangaden, Gj, Weavind, Lm, Young, Ma, Chen, St, Liu, E, Nguyen, Hh, Alfonso, Tb, Muse, Dd, Orenstein, R, Yacyshyn, B, Gebhard, Re, Dinges, W, Bolton, M, Rubin, M, Kuemmerle, Jf, Limaye, Ap, Friedenberg, Ka, Hiemenz, Jw, Quadri, A, Martinez, Jv, Barcan, La, Cordova, E, Mykietiuk, A, Losso, M, Fedorak, Rn, Steiner, T, Gerson, M, Weiss, K, Dlouhy, P, Vitous, A, Benes, J, Husa, P, Knizek, P, Anttila, Vj, Broas, M, Camou, F, Postil, D, Launay, O, Corroyer-Simovic, B, Meynard, Jl, Schneider, S, Molina, Jm, Neau, D, Zalcman, G, Boutoille, D, Ostermann, H, Heinz, W, Reuter, S, Oren, I, Schiff, E, Umemoto, T, Masubuchi, T, Mukawa, K, Yasuda, K, Imokawa, S, Fukuda, K, Ohta, H, Harada, N, Fujii, S, Tamaki, S, Yasui, S, Furukawa, K, Takahashi, M, Uraoka, T, Watanabe, M, Ikehara, Y, Kodaira, M, Komatsu, H, Higashi, K, Taguchi, F, Ura, N, Serizawa, Y, Fukuchi, T, Ashikawa, T, Shabana, M, Okubo, M, Matsumoto, M, Kurihara, A, Miyasaka, E, Shimizu, M, Tominaga, H, Kubota, T, Kashiwazaki, M, Masuda, Y, Terasaki, S, Okafuji, H, Mieno, H, Urabe, T, Okamoto, E, Kajimura, M, Yamagishi, Y, Rydzewska, G, Mach, T, Ciechanowski, K, Podlasin, R, Tomasiewicz, K, Janczewska-Kazek, E, Czarnobilski, K, Halota, W, Gryglewska, B, Plesniak, R, Dabrowiecki, P, Lipowski, D, Simanenkov, V, Shcheglova, L, Uspenskiy, Y, Cheganov, A, Han, Ds, Kim, Js, Hong, Sp, Kim, Ti, Jang, Bi, Byeon, Js, Kim, E, Kim, Mj, Lee, J, Pai, H, Cheong, Hj, Lee, S, Loyarte, Ja, Gonzalez, Jc, Santiago, Eb, Lopez, Jr, Baranda, Jm, Viladomiu, As, Calbo, E, Lannergard, A, Falt, J, Gardlund, B, Andersson, Lm, Fraenkel, Cj, Rombo, L, Widmer, A, Chen, Yc, Sheng, Wh, Wang, Fd, Wang, Nc, Lee, Ch, Chen, Yh, Chuang, Yc, Unal, S, Ozaras, R, Esen, S, Ural, O, Ayaz, C, Sakarya, S, Celebi, A, Mistik, R, Bedimo, R, Bressler, A, Mckinley, Mj, Quirk, D, Talansky, Al, Agronin, Me, Akhrass, Fa, Ali, M, Alrabaa, Sf, Assi, Ma, Calfee, Dp, Carson, P, Mariani, Pg, Guerrero, D, Dubberke, Er, Hardi, R, Hazan-Steinberg, S, Itani, Km, Jauregui-Peredo, El, Kasabji, A, Hameed, M, Murillo, A, Odio, Aj, Shah, P, Braun, Ti, Slim, J, Sloan, L, Srinivasan, S, Tan, Mj, Clough, La, Herr, D, Miller, Lg, Dorfmeister, J, Khan, O, and Melik-Abrahamian, F.
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0301 basic medicine ,Male ,Adolescent ,Adult ,Aged ,Aged, 80 and over ,Anti-Bacterial Agents ,Antibodies, Monoclonal ,Antibodies, Neutralizing ,Clostridium Infections ,Double-Blind Method ,Drug Therapy, Combination ,Female ,Humans ,Infusions, Intravenous ,Intention to Treat Analysis ,Kaplan-Meier Estimate ,Middle Aged ,Secondary Prevention ,Young Adult ,Clostridium difficile ,Clinical Trial, Phase III ,Antibiotics ,0302 clinical medicine ,Monoclonal ,80 and over ,030212 general & internal medicine ,Medicine (all) ,Neutralizing ,education.field_of_study ,Research Support, Non-U.S. Gov't ,General Medicine ,Multicenter Study ,Randomized Controlled Trial ,Combination ,Broadly Neutralizing Antibodies ,Intravenous ,medicine.medical_specialty ,Infusions ,medicine.drug_class ,030106 microbiology ,Population ,Placebo ,Antibodies ,03 medical and health sciences ,Pharmacotherapy ,Drug Therapy ,Internal medicine ,Journal Article ,medicine ,education ,Intention-to-treat analysis ,Clostridioides difficile ,business.industry ,Interim analysis ,Surgery ,Bezlotoxumab ,business - Abstract
BACKGROUND: Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively.METHODS: We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population.RESULTS: In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, -10.1 percentage points; 95% confidence interval [CI], -15.9 to -4.3; PCONCLUSIONS: Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239 .).
- Published
- 2017
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