1. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone
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Stempel, Da, Raphiou, Ih, Kral, Km, Yeakey, Am, Emmett, Ah, Prazma, Cm, Buaron, Ks, Pascoe, Sj, Austri, Investigators, Altieri, Hh, Antuni, Jd, Bergna, Ma, Cuadrado, Ja, De Gennaro MS, Fazio Lizandrelo CL, Gattolin, G, Gosn, Am, Larrateguy, Ld, Marcipar, Am, Maspero, Jf, Medina, Iv, Perez Chada RD, Silva, D, Victorio, Cf, Bardin, Pg, Carroll, Pa, Clements, Bs, Dore, Nd, Robinson, Pd, Fitzgerald, Da, Robinson, Pj, Russo, Ma, Sajkov, D, Thomas, Ps, Upham, Jw, Forstner, B, Kaik, G, Koeberl, Gh, Studnicka, M, Wallner, G, Balthazar, Y, Bauler, A, Dupont, Lj, Martinot, Jb, Ninane, V, Peché, R, Pilette, C, Dimitrova, R, Dimova, D, Kissyova Ibrishimova, G, Loboshka Becheva, M, Machkovska, M, Madjarov, S, Mandazhieva Pepelanova, M, Naidenova, I, Noleva, K, Takovska, N, Terziev, C, Aggarwal, Nk, Chapman, Kr, Csanadi, Ma, Dhillon, R, Henein, S, Kelly, Aj, Lam, As, Liem, Jj, Lougheed, Md, Lowe, Dw, Rizvi, Q, van den Berg, L, Zidel, B, Barros Monge MJ, Calvo Gil MA, Castillo Hofer CR, Diaz Amor PV, Lezana Soya, V, Quilodran Silva CN, Bolivar Grimaldos, F, Solarte-Rodriguez, I, Butkovic-Tomljanovic, R, Hegedus-Jungvirth, M, Ivkovic-Jurekovic, I, Simunov-Karuza, G, Buresova, M, Bursova, J, Fratrik, J, Guttlerova, E, Hartman, P, Jirmanova, I, Kalina, P, Kolman, P, Kucera, M, Povysilova, L, Pravda, P, Svabkova, A, Zakova, L, Backer, V, Maltbaek, N, Johnsen, Cr, Aries, Sp, Babyesiza, A, Barth, D, Benedix, A, Berg, P, Bergtholdt, B, Bettig, U, Bindig, Hw, Botzen, U, Brehler, R, Breyer, Go, Bruckhaus-Walter, M, Dapper, T, Eckhard, Jg, Engelhard, R, Feldmeyer, F, Fissan, H, Franz, Kh, Frick, Bs, Funck, J, Gessner, Cm, Ginko, T, Grigat, Ce, Grimm-Sachs, V, Groth, G, Hampf, J, Hanf, G, Havasi-Jost, G, Heinz, Gu, Helm, K, Hoeltz, S, Hofmann, S, Jander, R, Jandl, M, Jasch-Hoppe, B, Jung, T, Junggeburth, Jj, Kardos, P, Knueppel, W, Koch, T, Kolorz, C, Korduan, M, Korth-Wiemann, B, Krezdorn, Hg, Kroker, A, Kruell, M, Kuehne, P, Lenk, U, Liefring, E, Merke, J, Micke, L, Mitlehner, W, Mueller, H, Naudts, If, Neumann, G, Oldenburg, W, Overlack, A, Panzer, F, Reinholz, N, Remppis, R, Riegel, P, Rueckert, P, Schaetzl, Rj, Schauer, U, Hamelmann, E, Schenkenberger, I, Schlegel, V, Scholz, G, Schroers, M, Schwittay, A, Sebert, M, Tyler, K, Soemantri, Pa, Stock, P, Stuchlik, G, Unland, M, von Mallinckrodt, C, Wachter, J, Weber, U, Weberling, F, Wehgartner-Winkler, S, Weimer, J, Wiemer, S, Winkelmann, Ej, Zeisler, Kh, Ziegner, A, Zimny, Hh, Andrasofszky, Z, Bartha, A, Farkas, M, Gömöri, K, Kis, S, Major, K, Mészáros, I, Mezei, M, Rakvacs, M, Szalai, Z, Szántó, J, Szentesi, M, Szolnoki, E, Valyon, E, Zibotics, H, Anwar, J, Arimah, C, Djajalaksana, S, Rai, Ib, Setijadi, Ar, Setyanto, Db, Susanti, F, Syafiuddin, T, Syamsi, Ln, Wijanarko, P, Yunus, F, Bonavia, M, Braga, M, Chetta, Aa, Cerveri, I, Luisetti, M, Crimi, N, Cutrera, R, De Rosa, M, Esposito, S, Foresi, A, Gammeri, E, Iemoli, E, Legnani, Dl, Michetti, G, Pastorello, Ea, Pesci, A, Pistolesi, M, Riva, E, Romano, A, Scichilone, N, Terracciano, L, Tripodi, S, Choi, I, Kim, C, Kim, Js, Kim, Wj, Koh, Yy, Kwon, Ss, Lee, Sh, Lee, S, Lee, Sk, Park, Cs, Cirule, I, Eglite, R, Petrova, I, Poga, M, Smiltena, I, Chomiciene, A, Davoliene, I, Griskeviciene, V, Naudziunas, A, Naudziunas, S, Rudzeviciene, O, Sitkauskiene, B, Urbonas, G, Vaicius, D, Valavicius, A, Valiulis, A, Vebriene, J, bin Abdul Aziz FA, Daud, M, Ismail, Ai, Tengku Saifudin TI, Md Kassim RM, Mohd Fadzli FB, Wan Mohamad WH, Aguilar Dominguez PE, Aguilar-Orozco, Ra, Garza-Salinas, S, Ramirez-Diaz, Sp, Sánchez Llamas, F, Soto-Ramos, M, Velarde-Mora, Hj, Aguirre Sosa, I, Cisneros, Am, Estrella Viladegut RA, Matsuno Fuchigami, A, Adiaz-Baui, Tt, Bernan, Ap, Onia, Af, Sandagon, Mj, S-Naval, S, Yu, Cy, Bartuzi, Z, Bielous-Wilk, A, Błażowski, Ł, Bożek, A, Brzostek, J, Chorostowska-Wynimko, J, Ciekalska, K, Ziora, D, Cieslicki, J, Emeryk, A, Folcik, K, Gałuszka-Bilińska, A, Gawlik, R, Giejlo, M, Harat, R, Hofman, T, Jahnz-Różyk, K, Jedrzejczak, M, Kachel, T, Kamiński, D, Kelm Warchol, A, Konieczny, Z, Kwasniewski, A, Leszczyński, W, Mincewicz, G, Niezgoda, K, Olszewska-Ziąber, A, Onasz-Manitius, M, Pawlukiewicz, M, Piotrowicz, P, Piotrowski, W, Pisarczyk-Bogacka, E, Piskorz, P, Prokop-Staszecka, A, Roslan, A, Słomka, A, Smalera, E, Stelmach, I, Swierczynska-Krepa, M, Szmidt, M, Tarnowska-Matusiak, M, Tłuczykont, B, Tyminska, K, Waszkuc-Golonko, J, Wojciechowska, I, Alexandrescu, Ds, Neamtu, Ml, Todea, D, Alekseeva, E, Aleksandrova, E, Asherova, I, Barbarash, Ol, Bugrova, O, Bukreeva, Eb, Chermenskiy, A, Chizhova, O, Demko, I, Evdokimova, A, Giorgadze, Ml, Grigoryev, S, Irkhina, I, Khurkhurova, Nv, Kondyurina, Eg, Kostin, Vi, Kudelya, L, Laleko, Sl, Lenskaya, L, Levashov, S, Logvinenko, N, Martynov, A, Mizernitski, Y, Nemtsov, B, Novozhenov, Vg, Pavlishchuk, S, Popova, Vv, Reshetko, Ov, Sherenkov, A, Shirinsky, Vs, Shpagina, L, Soloviev, Ki, Tkachev, A, Trofimov, Vi, Vertkin, Al, Vorobeva, E, Idrisova, E, Yakushin, S, Zadionchenko, V, Zhiglinskaya, O, Zykov, K, Dopudja Pantic, V, Nadaskic, R, Nestorovic, B, Skodric Trifunovic, V, Stojanovic, A, Vukcevic, M, Vujic, T, Mitic Milikic, M, Banovcin, P, Horvathova, H, Karako, P Sr, Plutinsky, J, Pribulova, E, Szarazova, M, Zlatos, A, Adams, L, Badat, A, Bassa, A, Breedt, J, Bruning, A, Ellis, Gc, Emanuel, S, Fouche, Lf, Fulat, Ma, Gani, M, Ismail, Ms, Jurgens, Jc, Nell, H, Nieuwoudt, G, Noor, F, Bolliger, Ct, Puterman, As, Siddique, N, Trokis, Js, Vahed, Ya, Van Der Berg BJ, Van der Linden, M, Van Zyl, L, Visser, Ss, Antépara Ercoreca, I, Arnedillo Muñoz, A, Barbe Illa, F, Barreiro López, B, Blanco Aparicio, M, Boada Valmaseda, A, Bosque García, M, Bustamante Ruiz, A, Carretero Anibarro, P, Del Campo Matias, F, Echave-Sustaet, Jm, Espinosa de los Monteros Garde MJ, Garcia Hernandez GM, López Viña, A, Lores Obradors, L, Luengo Planas MT, Monsó Molas, E, Navarro Dourdil, A, Nieto García AJ, Perpina Tordera, M, Picado Valles, C, Rodriguez Alvarez Mdel, M, Saura Vinuesa, A, Serra Batlles, J, Soler Sempere MJ, Toran Montserrat, P, Valdés Cuadrado LG, Villasante Fernandez-Montes, C, Cheng, Sl, Chern, Jh, Chiu, Mh, Chung, Cl, Lai, Rs, Lin, Ck, Liu, Yc, Wang, Cc, Wei, Yf, Amer, L, Berenfus, Vi, Besh, L, Duka, Kd, Fushtey, Im, Garmash, N, Dudnyk, O, Godlevska, O, Vlasenko, Ma, Hospodarskyy, I, Iashyna, L, Kaladze, M, Khvelos, Si, Kostromina, Vp, Krakhmalova, O, Kryuchko, T, Kulynych, Ov, Krasko, Mp, Levchenko, O, Litvinova, T, Panina, Ss, Pasiyeshvili, Lm, Prystupa, Ln, Romaniuk, Li, Sirenko, I, Synenko, Vi, Vynnychenko, Lb, Yatsyshyn, Ri, Zaitsev, I, Zhebel, V, Zubarenko, O, Arthur, Cp, Brown, V, Burhan, H, Chaudhuri, R, Collier, D, Barnes, Nc, Davies, Ej, Ellery, A, Kwok, S, Lenney, W, Nordstrom, M, Pandya, Hc, Parker, Iw, Rajakulasingam, K, Seddon, P, Sharma, R, Thomas, Ec, Wakeling, Ja, Abalos-Galito, M, Abboy, C, Abreu, E, Ackerman, If, Acosta, Ia, Adaoag, Aa, Ahmed, M, Ali, Mi, Allen, Dr, Allen GG Jr, Diogo, Jj, Allison, Dc, Alwine, Lk, Apaliski, Sj, Arastu, Rs, Arora, Cm, Auerbach, D, Azzam, Sj, Badar FL 3rd, Baker, Jw, Barasch, Jp, Barber, Ma, Bardinas-Rodriguez, R, Barreiro, Tj, Baumbach, Rr, Baur, Ce, Baxter, Bs, Beach, Jl, Beasley, Rl, Beavins, Je, Beliveau, Wj, Benbow, Mj, Bennett, Nl, Bennett, Rl, Bernal, H, Bernstein, Di, Blaiss, Ms, Blumenthal, Kw, Boas, Sr, Borders, Jl, Boscia, Ja, Boulware, Wn, Bowling, Bt, Brabec, Ba, Bramlet, Dg, Figueroa, Dp, Brautigam, Df, Brownell, Jm, Bruce, Tr, Call, Rs, Campbell, Ca, Canaan, Ya, Cannon, Df, Carpio, Jm, Cathcart, Ws, Cevallos, Jp, Chauhan, Av, Chuang, Rb, Chevalier, D, Christensen, J, Christensen, Ta, Christina, Mo, Chrzanowski, Rr, Civitarese, Fa, Clark, Jp, Clifford, Dp, Lapidus, Rj, Coggi, Ja, Lenz, Jj, Cohen, Kr, Collins, Bg, Collins, H, Comellas, A, Condit, J, Cordasco EM Jr, Corder, Cn, Covar, Ra, Coverston, Kd, Croce, Sa, Cruz, H, Curtis, Ct, Daftary, Pk, Dalan, D, Dalawari, Sp, Daly, Wc, Davis, Kc, Dawes, Kw, Decotiis, Ba, Deluca, Rf, Desantis, Dm, De Valle OL, Diaz, Jl, Diaz, Jd, Dice, Jp, Elizalde, A, Hosler, Mr, Dixon, C, Dobkin, La, Dobrusin, Rs, Dransfield, Mt, Ebbeling, Wl, Edwards, Jd, Elacion, Jm, Elkayam, D, Ellison, Wt, Elsen, Jr, Engel, Lr, Ensz, Dj, Ericksen, Cl, Ervin, Je, Fang, C, Abrahamian, F, Farrah, Vb, Field, Jd, Fishman, Hj, Florea, R, Nayyar, S, Focil, A, Focauld, F, Franco MA Jr, Frandsen, Br, Ganti, K, Garcia, Fl, Lee, Wm, Garscadden, Ag, Gatti, Ea, Gellady, Am, George, Ar, Gibbon, Gw, Gleason, Gp, Goldberg, P, Goldstein, Mf, Gonzalez, Ge, Gower, Rg, Grande, Ja, Gregory, D, Grubb, Sd, Guthrie, Rp, Haas, Ta, Haft, Ks, Hajal, R, Hammond, Gd, Hansel, Nn, Hansen, Vr, Harris, Af, Hartman, An, Harvey, Rr, Hazan-Steinberg, S, Headley, Dm, Heigerick, Gc, Heller, Bn, Hendrix, El, Herrod, Jn, Hewitt, Mj, Hines, Rl, Hirdt, Ap, Hirschfield, Ja, Hoffman, Ks, Hogan, Ad, Howland, Wc, Hsu, Cc, Hsu, Fj, Hubbard, Wm, Hudson, Jd, Huffman, C, Hussain, M, Ioachimescu, Oc, Ismail, Ym, Jaffrani, Na, Jiang, N, Jones, Sw, Jordan, Rs, Joshi, Ke, Kaashmiri, Mw, Kalafer, M, Kamdar, Ba, Kanuga, Jg, Kao, Nl, Karetzky, M, Katsetos, Jc, Kay, Js, Kimmel, Ma, Kimura, Sh, Kingsley, Jk, Mahmood, Sm, Subich, Dc, Kirstein, Jl, Kleerup, Ec, Klein, Rm, Koh, Dw, Kohli, N, Koura, Fa, Kovacs, Sp, Kratzer, J, Kreit, Ci, Kreutter, Fm, Kubicki, Tm, Labuda, Jm, Latorre, Aj, Lara, Mm, Lechin, Ae, Lee, Jj, Lee, Md, Lentnek, Al, Lesh, Kw, Levins, Pf, Anspach, Rb, Levinsky, Dm, Lillestol, Mj, Lim, H, Livezey, Md, Lloyd-Turney, Cw, Lockey, Rf, Long, Ra, Lynch, Mj, Macgillivray, Bk, Mahadevan, Kp, Makam, Sk, Maloney, Mj, Mapel, D, Margolis, Bd, Margulies, J, Martin, Ef, Martin, Ee, Mascolo, M, Mataria, H, Sunbuli, M, Mathur, Rn, Mattar, Pn, Maynard, Km, Maynard, N, Mccormick, B, Mcelya, M, Mcevoy, Ce, Mckenzie, Wc, Medwedeff, Le, Mehta, Kd, Melamed, Ir, Meli, Jv, Merrick, Bh, Meyers, Pj, Miller, Bt, Minton, Sm, Miranda, Fg, Mohar, De, Montenegro, Ch, Morris, Fa, Morrison, Bs, Moss, Mh, Munoz, F, Naini, Gr, Nakamura, Ct, Naseeruddin, S, Nassim, C, Navazo, Lj, Nissim, Je, Norman, D, Oberoi, Ms, O'Connor, Tm, Offenberger, J, Orr, Rr, Osea, Ea, Paine, Wj, Rasmussen, Nl, Palatnik, M, Pangtay, D, Panuto, Ja, Patel, M, Perera, Ms, Perez, A, Peters PH Jr, Pimentel SM Jr, Pluto, Tm, Pollock, Mt, Posner, Ls, Pritchard, Jc, Pudi, Kk, Puig, Cm, Qaqundah, Py, Radbill, Mk, Rahman, St, Raikhel, M, Raissy, Hh, Ramstad, Ds, Ranasinghe, Es, Rangel, Os, Rapo, Se, Raschal, Sp, Reddy, Dg, Rehman, Sm, Reyes, Sr, Rhodes, Rb, Riffer, E, Rihal, Ps, Riley ED 4th, Rodriguez, Dh, Rogers, Cm, Rohlf, Jl, Romeu, H, Roney, Cw, Ronsick, So, Rosen, Jb, Rowe, Ms, Ruoff, Ge, Ryan, Eh, Saff, Rh, Saini, N, Anand, S, Balakrishnan, K, Samuels, Bs, Samuelson, Rj, Saniuk, Rj, Sargeant, Wo, Saunders, Mk, Saway, W, Scarupa, Md, White, Mv, Schear, Mj, Schwarz, Cm, Scott, Rb, Segall, N, Seibert, Af, Seidmeyer, V, Seidner, Mr, Seifer, Fd, Serje, J, Shah, Ms, Shah, Sb, Shapero, Pa, Shearer, Sd, Sheikh, Sq, Shepherd, Ts, Sher, Er, Sher, Ld, Short, Bh, Silas, Pe, Alvey, Jc, Silverfield, Jc, Simon, Sj, Sitar, S, Skoner, Dp, Smallow, Sa, Smart, Ba, Smith, Ca, Smith, Ke, Smith, Sk, Snyders, Gc, Soong, W, Soufer, J, Spangenthal, S, Stahlman, Je, Steele, Lg, Stegemoller, Rk, Stocks, J, Storms, Ww, Suen, J, Surowitz, Rz, Swauger, Jr, Taber, La, Tan, Ae, Pratt, Se, Tanus, T, Tarpay, Mm, Tarshis, Ga, Tenney, Jw, Tilghman, Kg, Trevino, Me, Troyan, Be, Twiddy, Sk, Updegrove, Jd, Urval, Kr, Uusinarkaus, Kt, Vaela, R, Van Cleeff, M, Varano, S, Vo, Qd, Wainz, Rj, Wald, Ja, Wall, Sj, Wasserman, Rl, Weinstein, Dl, Welker, Ja, Wellmon, B 2nd, Wells, T, Wenocur, Hs, Williams, Dl, Williams, Sl, Win, Ph, Wingo, Td, Wisman PP Jr, Wyszomierski, Da, Yamada, Hm, Yarows, S, Yunger TM Jr, Ziering, Rw., the AUSTRI Investigators, Stempel, D., Raphiou, I., Kral, K., Yeakey, A., Emmett, A., Prazma, C., Buaron, K., and Pascoe, S. Scichilone N tra i collaboratori
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Male ,asthma ,serious events ,fluticasone ,salmeterol ,AUSTRI ,Exacerbation ,Intention to Treat Analysi ,INHALED CORTICOSTEROIDS ,Severity of Illness Index ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,immune system diseases ,Ús terapèutic ,Broncodilatadors ,030212 general & internal medicine ,Child ,Fluticasone ,RISK ,ACTING BETA-AGONISTS ,EXACERBATIONS ,METAANALYSIS ,MORTALITY ,SAFETY ,DEATH ,FDA ,Medicine (all) ,Hazard ratio ,General Medicine ,Bronchodilator agents ,Middle Aged ,Fluticasone-Salmeterol Drug Combination ,Bronchodilator Agents ,Intention to Treat Analysis ,Anesthesia ,Female ,Salmeterol ,medicine.drug ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Fluticasone propionate ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Administration, Inhalation ,medicine ,Humans ,Asma ,Bronchodilator Agent ,Asthma ,Aged ,Proportional Hazards Models ,business.industry ,Therapeutic use ,medicine.disease ,respiratory tract diseases ,030228 respiratory system ,Fluticasone Propionate, Salmeterol Xinafoate Drug Combination ,Proportional Hazards Model ,business - Abstract
BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone–salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone–salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone–salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone–salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone–salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P
- Published
- 2016