Search

Your search keyword '"Wencel, M"' showing total 6 results
Start Over Author "Wencel, M" Topic humans
6 results on '"Wencel, M"'

1. Reconciling Healthcare Professional and Patient Perspectives in the Development of Disease Activity and Response Criteria in Connective Tissue Disease Related Interstitial Lung Diseases

Author

Saketkoo, La, Mittoo, S, Frankel, S, Lesage, D, Sarver, C, Phillips, K, Strand, V, Matteson, El, OMERACT Baughman RP, Brown, Kk, Christmann, Rb, Dellaripa, P, Denton, Cp, Distler, O, Fischer, A, Flaherty, K, Huscher, D, Khanna, D, Kowal Bielecka, O, Merkel, Pa, Oddis, Cv, Pittrow, D, Sandorfi, N, Seibold, Jr, Swigris, J, Wells, A, Antoniou, K, Castelino, Fv, Christopher Stine, L, Collard, Hr, Cottin, V, Danoff, S, Hedlund, R, Highland, Kb, Hummers, L, Lynch, Da, Kim, Ds, Ryu, Jh, Miller, Fw, Nichols, K, Proudman, Sm, Richeldi, L, Shah, Aa, van den Assum, P, Aggarwal, R, Ainslie, G, Alkassab, F, Allanore, Y, Anderson, Me, Andonopoulos, Ap, Antin Ozerkis, D, Arrobas, A, Ascherman, Dp, Assassi, S, Baron, M, Bathon, Jm, Baughman, Rp, Behr, J, Beretta, L, Bingham, Co, Binnie, M, Birring, Ss, Boin, F, Bongartz, T, Bourdin, A, Bouros, D, Brasington, R, Bresser, P, Buch, Mh, Burge, Ps, Carmona, L, Carreira, Pe, Carvalho, Cr, Catoggio, Lj, Chan, Km, Chapman, J, Chatterjee, S, Chua, F, Chung, L, Conron, M, Corte, T, Cosgrove, G, Costabel, U, Cox, G, Crestani, B, Crofford, Lj, Csuka, Me, Curbelo, P, Czirják, L, Daniil, Z, D'Arsigny, Cl, Davis, Gs, de Andrade JA, Dellaripa, Pf, De Vuyst, P, Dempsey, Oj, Derk, Ct, Distler, J, Dixon, Wg, Downey, G, Doyle, Mk, Drent, M, Durairaj, L, Emery, P, Espinoza, Lr, Farge, D, Fathi, M, Fell, Cd, Fessler, Bj, Fitzgerald, Je, Flaherty, Kr, Foeldvari, I, Fox, Ga, Frech, Tm, Freitas, S, Furst, De, Gabrielli, A, García Vicuña, R, Georgiev, Ob, Gerbino, A, Gillisen, A, Gladman, Dd, Glassberg, M, Gochuico, Br, Gogali, A, Goh, Ns, Goldberg, A, Goldberg, Hj, Gourley, Mf, Griffing, L, Grutters, Jc, Gunnarsson, R, Hachulla, E, Hall, Fc, Harari, S, Herrick, Al, Herzog, El, Hesselstrand, R, Highland, K, Hirani, N, Hodgson, U, Hollingsworth, Hm, Homer, Rj, Hoyles, Rk, Hsu, Vm, Hubbard, Rb, Hunzelmann, N, Isasi, Me, Isasi, Es, Jacobsen, S, Jimenez, Sa, Johnson, Sr, Jones, Ch, Kahaleh, B, Kairalla, Ra, Kalluri, M, Kalra, S, Kaner, Rj, Kinder, Bw, Kiter, G, Klingsberg, Rc, Kokosi, M, Kolb, Mr, Kowal Bielecka OM, Kur Zalewska, J, Kuwana, M, Lake, Fr, Lally, Ev, Lasky, Ja, Laurindo, Im, Able, L, Lee, P, Leonard, Ct, Lien, Dc, Limper, Ah, Liossis, Sn, Lohr, Km, Loyd, Je, Lundberg, Ie, Mageto, Yn, Maher, Tm, Mahmud, Th, Manganas, H, Marie, I, Marras, Tk, Martinez, Ja, Martinez, Fj, Mathieu, A, Matucci Cerinic, M, Mayes, Md, Mckown, Km, Medsger, Ta, Meehan, Rt, Mendes, Ac, Meyer, Kc, Millar, Ab, Moğulkoc, N, Molitor, Ja, Morais, A, Mouthon, L, Müller, V, Müller Quernheim, J, Nadashkevich, O, Nador, R, Nash, P, Nathan, Sd, Navarro, C, Neves, S, Noth, I, Nunes, H, Olson, Al, Opitz, Cf, Padilla, M, Pappas, D, Parfrey, H, Pego Reigosa JM, Pereira, Ca, Perez, R, Pope, Je, Porter, Jc, Renzoni, Ea, Riemekasten, G, Riley, Dj, Rischmueller, M, Rodriguez Reyna TS, Rojas Serrano, J, Roman, J, Rosen, Gd, Rossman, M, Rothfield, N, Sahn, Sa, Sanduzzi, A, Scholand, Mb, Selman, M, Senécal, Jl, Seo, P, Shah, A, Silver, Rm, Solomon, Jj, Steen, V, Stevens, W, Strange, C, Sussman, R, Sutton, Ed, Sweiss, Nj, Tornling, G, Tzelepis, Ge, Undurraga, A, Vacca, A, Vancheri, Carlo, Varga, J, Veale, Dj, Volkov, S, Walker, Ua, Wells, Au, Wencel, M, Wesselius, Lj, Wickremasinghe, M, Wilcox, P, Wilsher, Ml, Wollheim, Fa, Wuyts, Wa, Yung, G, Zanon, P, Zappala, Cj, Groshong, Sd, Leslie, Ko, Myers, Jl, Padera, Rf, Desai, Sr, Goldin, J, Kazerooni, Ea, Klein, Js, and Keen, Kj

Subjects
Male, medicine.medical_specialty, Delphi Technique, Consensus Development Conferences as Topic, Health Personnel, Immunology, Context (language use), Disease, Severity of Illness Index, Article, Idiopathic pulmonary fibrosis, Rheumatology, medicine, Immunology and Allergy, Humans, Disease management (health), Intensive care medicine, Connective Tissue Diseases, Randomized Controlled Trials as Topic, business.industry, Interstitial lung disease, Disease Management, respiratory system, Focus Groups, medicine.disease, Comorbidity, Connective tissue disease, respiratory tract diseases, Clinical trial, Treatment Outcome, Patient Satisfaction, Physical therapy, Quality of Life, ÍNDICE DE GRAVIDADE DA DOENÇA, Interdisciplinary Communication, business, Lung Diseases, Interstitial
Abstract

Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

Published
2014

2. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis

Author

Luca, Richeldi, du Bois, Roland M., Ganesh, Raghu, Arata, Azuma, Brown, Kevin K., Ulrich, Costabel, Vincent, Cottin, Flaherty, Kevin R., Hansell, David M., Yoshikazu, Inoue, Dong Soon Kim, Martin, Kolb, Nicholson, Andrew G., Noble, Paul W., Moisés, Selman, Hiroyuki, Taniguchi, Michèle, Brun, Florence Le Maulf, Mannaïg, Girard, Susanne, Stowasser, Rozsa Schlenker Herceg, Bernd, Disse, Collard, Harold R., Corte, T, Davies, H, Glaspole, I, Mulder, J, Veitch, E, De Vuyst, P, Liistro, G, Sibille, Y, Vincken, W, Wuyts, W, Fell, C, Hernandez, P, Kolb, M, Undurraga, A, Bai, C, Chen, P, Gao, Z, Kang, J, Li, H, Li, Z, Wan, H, Wang, H, Wen, F, Xiao, Q, Xu, Z, Zhang, W, Zheng, X, Zhu, H, Pauk, N, Reiterer, P, Vasakova, M, Hodgson, U, Bourdin, A, Cadranel, J, Camus, P, Chanez, P, Cottin, V, Crestani, B, Israel Biet, D, Jouneau, S, Lebargy, F, Marquette, C, Prévot, G, Valeyre, D, Wallaert, B, Bonnet, R, Costabel, U, Gläser, S, Grohé, C, Guenther, A, Hammerl, P, Höffken, G, Karagiannidis, C, Kirschner, J, Kirsten, A, Korn, S, Kreuter, M, Müller Quernheim, J, Neurohr, C, Pfeifer, M, Schönfeld, N, Wiewrodt, R, Antoniou, K, Daniil, Z, Diamantea, F, Koulouris, N, Mathioudakis, G, Ghosal, A, Kadappa Shivappa, S, Kawedia, M, Khatavkar, P, Kumar, A, Mehta, P, Singh, V, Srikanth, K, Thakker, H, Udwadia, Z, Egan, J, Fink, G, Kramer, M, Yigla, M, Agostini, Carlo, De Benedetto, F, Harari, S, Luppi, F, Paggiaro, P, Tavanti, L, Pesci, A, Poletti, V, Rottoli, P, Saltini, C, Sanduzzi Zamparelli, A, Vancheri, C, Bando, M, Hasegawa, Y, Hashimoto, K, Homma, S, Inase, N, Inoue, Y, Arai, T, Izumi, S, Kawamura, T, Kishi, K, Kondo, Y, Kuwano, K, Miura, Y, Nishioka, Y, Nishiyama, O, Ogura, T, Ohkouchi, S, Saito, T, Setoguchi, Y, Shindoh, J, Taguchi, Y, Tanakadate, M, Tomii, K, Sugita, Y, Yamaguchi, T, Yoshimori, K, Jeong, S, Kim, D, Kim, Y, Park, C, Song, J, Uh, S, Selman, M, Bresser, P, Grutters, J, Wijsenbeek, M, Arrobas, A, Cardoso, J, Costa, R, Morais, A, Neves, S, Serrado, M, Ilkovick, M, Vizel, A, Alfageme Michavila, I, Ancochea, J, Castillo Villegas, D, Molina Molina, M, Morell, F, Xaubet, A, Aktogu Ozkan, S, Kayacan, O, Ongen, G, Mogulkoc, N, Tuncay, E, Beirne, P, Bettinson, H, Burge, P, Dempsey, O, Maher, T, Millar, A, Spencer, L, Thickett, D, Alvarez, J, Andrews, C, Bajwa, O, Baker, A, Baughman, R, Belperio, J, Bradley, J, Collard, H, Cordova, F, Daniels, C, de Andrade, J, Dushay, K, Enelow, R, Ettinger, N, Gibson, K, Gotfried, M, Hajari Case, A, Hotchkin, D, Huggins, J, Kaye, M, Kershaw, C, Kureishy, S, Lancaster, L, Lederer, D, Mageto, Y, Masson, J, Meyer, K, Mohabir, P, Morrison, L, Nathan, S, Noth, I, Oelberg, D, Rahaghi, F, Riley, D, Rizzo, A, Rossman, M, Ruzi, J, Sachs, P, Schaumberg, T, Scholand, M, Schroeder, C, Seifer, F, Shea, J, Sinkowitz, D, Tabak, J, Taylor, J, Thompson, J, Thurm, C, Tita, J, Wencel, M, Westerman, J, Lasky, J, Demedts, M, Casteels, M, Loddenkemper, R, Michaelis, J, Roman, J, Tino, G, Luisetti, M., and Clinical sciences

Subjects
Male, medicine.medical_specialty, Vital capacity, Indoles, Exacerbation, Aged, Disease Progression, Double-Blind Method, Enzyme Inhibitors, Female, Humans, Idiopathic Pulmonary Fibrosis, Middle Aged, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Quality of Life, Treatment Outcome, Vital Capacity, Settore MED/10 - Malattie dell'Apparato Respiratorio, Medizin, Placebo, Gastroenterology, FEV1/FVC ratio, Idiopathic pulmonary fibrosis, chemistry.chemical_compound, Internal medicine, medicine, business.industry, Medicine (all), Hazard ratio, General Medicine, Pirfenidone, medicine.disease, Surgery, chemistry, Nintedanib, business, medicine.drug
Abstract

Background Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. Methods We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George’s Respiratory Questionnaire, both assessed over a 52-week period. Results A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was −114.7 ml with nintedanib versus −239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P

Published
2014

3. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: Provisional core sets of domains and instruments for use in clinical trials

Author

Saketkoo, La, Mittoo, S, Huscher, D, Khanna, D, Dellaripa, Pf, Distler, O, Flaherty, Kr, Frankel, S, Oddis, Cv, Denton, Cp, Fischer, A, Kowal Bielecka OM, Lesage, D, Merkel, Pa, Phillips, K, Pittrow, D, Swigris, J, Antoniou, K, Baughman, Rp, Castelino, Fv, Christmann, Rb, Christopher Stine, L, Collard, Hr, Cottin, V, Danoff, S, Highland, Kb, Hummers, L, Shah, Aa, Kim, Ds, Lynch, Da, Miller, Fw, Proudman, Sm, Richeldi, L, Ryu, Jh, Sandorfi, N, Sarver, C, Wells, Au, Strand, V, Matteson, El, Brown, Kk, Seibold, Jr, Aggarwal, R, Ainslie, G, Alkassab, F, Allanore, Y, Descartes, P, Anderson, Me, Andonopoulos, Ap, Antin Ozerkis, D, Arrobas, A, Ascherman, Dp, Assassi, S, Baron, M, Bathon, Jm, Behr, J, Beretta, L, Bingham, Co, Binnie, M, Birring, Ss, Boin, F, Bongartz, T, Bourdin, A, Bouros, D, Brasington, R, Bresser, P, Buch, Mh, Burge, Ps, Carmona, L, Carreira, Pe, Carvalho, Cr, Catoggio, Lj, Chan, Km, Chapman, J, Chatterjee, S, Chua, F, Chung, L, Conron, M, Corte, T, Cosgrove, G, Costabel, U, Cox, G, Crestani, B, Crofford, Lj, Csuka, Me, Curbelo, P, László, C, Daniil, Z, D'Arsigny, Cl, Davis, Gs, de Andrade JA, De Vuyst, P, Dempsey, Oj, Derk, Ct, Distler, J, Dixon, Wg, Downey, G, Doyle, Mk, Drent, M, Durairaj, L, Emery, P, Espinoza, Lr, Farge, D, Fathi, M, Fell, Cd, Fessler, Bj, Fitzgerald, Je, Fox, Ga, Foeldvari, I, Frech, Tm, Freitas, S, Furst, De, Gabrielli, A, García Vicuña, R, Georgiev, Ob, Gerbino, A, Gillisen, A, Gladman, Dd, Glassberg, M, Gochuico, Br, Gogali, A, Goh, Ns, Goldberg, A, Goldberg, Hj, Gourley, Mf, Griffing, L, Grutters, Jc, Gunnarsson, R, Hachulla, E, Hall, Fc, Harari, S, Herrick, Al, Herzog, El, Hesselstrand, R, Hirani, N, Hodgson, U, Hollingsworth, Hm, Homer, Rj, Hoyles, Rk, Hsu, Vm, Hubbard, Rb, Hunzelmann, N, Isasi, Me, Isasi, Es, Jacobsen, S, Jimenez, Sa, Johnson, Sr, Jones, Ch, Kahaleh, B, Kairalla, Ra, Kalluri, M, Kalra, S, Kaner, Rj, Kinder, Bw, Klingsberg, Rc, Kokosi, M, Kolb, Mr, Kur Zalewska, J, Kuwana, M, Lake, Fr, Lally, Ev, Lasky, Ja, Laurindo, Im, Able, L, Lee, P, Leonard, Ct, Lien, Dc, Limper, Ah, Liossis, Sn, Lohr, Km, Loyd, Je, Lundberg, Ie, Mageto, Yn, Maher, Tm, Mahmud, Th, Manganas, H, Marie, I, Marras, Tk, Antônio Baddini Martinez, J, Martinez, Fj, Mathieu, A, Matucci Cerinic, M, Mayes, Md, Mckown, Km, Medsger, Ta, Meehan, Rt, Cristina, Ma, Meyer, Kc, Millar, Ab, Moğulkoc, N, Molitor, Ja, Morais, A, Luc Mouthon, P, Müller, V, Müller Quernheim, J, Nadashkevich, O, Nador, R, Nash, P, Nathan, Sd, Navarro, C, Neves, S, Noth, I, Nunes, H, Olson, Al, Opitz, Cf, Padilla, M, Pappas, D, Parfrey, H, Pego Reigosa JM, Pereira, Ca, Perez, R, Pope, Je, Porter, Jc, Renzoni, Ea, Riemekasten, G, Riley, Dj, Rischmueller, M, Rodriguez Reyna TS, Rojas, Serrano, Roman, J, Rosen, Gd, Rossman, M, Rothfield, N, Sahn, Sa, Sanduzzi, A, Scholand, Mb, Selman, M, Senécal, Jl, Seo, P, Silver, Rm, Solomon, Jj, Steen, V, Stevens, W, Strange, C, Sussman, R, Sutton, Ed, Sweiss, Nj, Tornling, G, Tzelepis, Ge, Undurraga, A, Vacca, A, Vancheri, Carlo, Varga, J, Veale, Dj, Volkov, S, Walker, Ua, Wencel, M, Wesselius, Lj, Wickremasinghe, M, Wilcox, P, Wilsher, Ml, Wollheim, Fa, Wuyts, Wa, Yung, G, Zanon, P, Zappala, Cj, Groshong, Sd, Leslie, Ko, Myers, Jl, Padera, Rf, Desai, Sr, Goldin, J, Kazerooni, Ea, Klein, Js, Cenac, Sl, Grewal, Hk, Christensen, Am, Ferguson, S, Tran, M, Keen, K. J., Costabel, Ulrich (Beitragende*r), Raynauds & Scleroderma Association, Arthritis Research UK, The Scleroderma Society, and British Lung Foundation

Subjects
Lung Diseases, Connective tissue disease associated lung disease, CTD-ILD Special Interest Group, International Cooperation, Respiratory System, Medizin, Rheumatoid lung disease, Idiopathic pulmonary fibrosis, Quality of life, QUALITY-OF-LIFE, CYCLOPHOSPHAMIDE, SCLERODERMA LUNG, Registries, Connective Tissue Diseases, Societies, Medical, Randomized Controlled Trials as Topic, Interstitial lung disease, respiratory system, Connective tissue disease, Interstitial Fibrosis, medicine.anatomical_structure, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Consensus, Clinical Sciences, END-POINT, Interstitial Lung Disease, Systemic disease and lungs, Medical, medicine, Humans, ENSAIO CLÍNICO CONTROLADO RANDOMIZADO, VALIDITY, Intensive care medicine, Lung, Science & Technology, COUGH, business.industry, Clinical study design, MORTALITY, SYSTEMIC-SCLEROSIS, 1103 Clinical Sciences, Congresses as Topic, medicine.disease, GEORGES RESPIRATORY QUESTIONNAIRE, respiratory tract diseases, Clinical trial, IPF, Physical therapy, Interstitial, Societies, business, Lung Diseases, Interstitial
Abstract

Rationale: Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods: The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results: A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion: Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Published
2014

4. Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial

Author

Raghu, G, Million Rousseau, R, Morganti, A, Perchenet, L, Behr, J, Goh, N, Glanville, A, Musk, M, Hopkins, P, Lien, D, Chan, C, Rolf, J, Wilcox, P, Cox, P, Manganas, H, Cottin, V, Valeyre, D, Walleart, B, Andreas, S, Neurohr, C, Guenther, A, Schonfeld, N, Koch, A, Kramer, M, Breuer, R, Ben Dov, I, Fink, G, Schwarz, Y, Albera, C, Confalonieri, M, Saltini, C, Harari, S, Flezar, M, Greenblatt, M, Ras, G, Morell, F, Alvarez Sala, J, Xaubet, A, Sueiro, A, Linares, M, Sko, M, Kayacan, O, Mogulkoc, N, Chan, A, Chapman, J, Parambil, J, Ettinger, N, Meyer, K, Swigris, J, Yung, G, Antin Ozerkis, D, Mohabir, P, Wesselius, L, de Andrade, J, Cordova, F, Safdar, Z, Wencel, M, O'Connor, C, Nashan, B, Demets, D, Gray, A, Raghu, G, Million-Rousseau, R, Morganti, A, Perchenet, L, Behr, J, Goh, N, Glanville, A, Musk, M, Hopkins, P, Lien, Dc, Chan, C, Rolf, Jd, Wilcox, P, Cox, Pg, Manganas, H, Cottin, V, Valeyre, D, Wallear, B, Andreas, S, Neurohr, C, Guenther, A, Schönfeld, N, Koch, A, Kramer, M, Breuer, R, Ben-Dov, I, Fink, G, Schwarz, Y, Albera, C, Confalonieri, M, Et, Al, and Ege Üniversitesi

Subjects
Endothelin Receptor Antagonists, Male, Vital capacity, Settore MED/10 - Malattie dell'Apparato Respiratorio, Vital Capacity, Gastroenterology, Pulmonary function testing, law.invention, chemistry.chemical_compound, Idiopathic pulmonary fibrosis, Randomized controlled trial, Usual interstitial pneumonia, law, Forced Expiratory Volume, Prospective Studies, Aged, 80 and over, Sulfonamides, Alanine Transaminase, Middle Aged, ComputingMilieux_MANAGEMENTOFCOMPUTINGANDINFORMATIONSYSTEMS, Treatment Outcome, Liver, Female, InformationSystems_MISCELLANEOUS, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Placebo, Double-Blind Method, Internal medicine, medicine, Humans, controlled study, Aspartate Aminotransferases, Aged, Macitentan, idiopathic pulmonary fibrosis, macicentan, idiopathic pulmonary fibrosi, Endothelin receptor antagonist, business.industry, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, medicine.disease, Idiopathic Pulmonary Fibrosis, Surgery, ComputingMethodologies_PATTERNRECOGNITION, Dyspnea, Pyrimidines, chemistry, business
Abstract

PubMed ID: 23682110, Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of, Actelion Pharmaceuticals Ltd.

Published
2013

5. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial

Author

King TE Jr, Albera, C, Bradford, Wz, Costabel, U, Hormel, P, Lancaster, L, Noble, Pw, Sahn, Sa, Szwarcberg, J, Thomeer, M, Valeyre, D, du Bois RM, INSPIRE Study Group, Agostini, Carlo, Allen, J, Anzueto, A, Behr, J, Bonnet, R, Buhl, R, Burge, S, Chan, A, Chan, C, Chanez, P, Chapman, J, Cordier, J, Covelli, H, Crimi, N, de Andrade, J, Delaval, P, Dromer, C, Egan, J, Enelow, R, Ettinger, N, Flaherty, K, Floreani, A, Frankel, S, Frost, A, Gibson, K, Glassberg, M, Gottfried, M, Harari, S, Helmersen, D, Hollingsworth, H, Horton, M, Jennings, J, Kallay, M, Lasky, J, Lee, A, Leonard, C, Lorch, D, Lynch, J, Mageto, Y, Mette, S, Millar, A, Morell Brotad, F, Müller Quernheim, J, Nathan, S, Noth, I, Padilla, M, Poletti, V, Raghu, G, Richeldi, L, Robbins, M, Rolf, J, Roman, J, Rosen, G, Rottoli, P, Saltini, C, Schaberg, T, Schaumberg, T, Scholand, M, Schönfeld, N, Sharma, S, Simonelli, P, Steele, M, Sussman, R, Tino, G, Vogelmeier, C, Wallaert, B, Wells, A, Wencel, M, Wesselius, L, Whelan, T, Wilcox, P, Wolters, P, Xaubet, A, and Zisman, D.

Subjects
Male, medicine.medical_specialty, Settore MED/10 - Malattie dell'Apparato Respiratorio, Injections, Subcutaneous, Vital Capacity, Placebo-controlled study, Kaplan-Meier Estimate, Placebo, Severity of Illness Index, Drug Administration Schedule, Pulmonary function testing, Injections, Idiopathic pulmonary fibrosis, Interferon-gamma, Double-Blind Method, Internal medicine, Pulmonary fibrosis, medicine, Humans, Aged, Analysis of Variance, Disease Progression, Europe, Exercise Test, Female, Idiopathic Pulmonary Fibrosis, North America, Proportional Hazards Models, Pulmonary Diffusing Capacity, Recombinant Proteins, Survival Rate, Treatment Failure, Medicine (all), Survival rate, business.industry, Subcutaneous, Hazard ratio, General Medicine, Interim analysis, medicine.disease, Surgery, business
Abstract

Summary Background Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists. We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function. Methods 826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries, the USA, and Canada. Patients were randomly assigned (double-blind) in a 2:1 ratio to receive 200 μg interferon gamma-1b (n=551) or equivalent placebo (n=275) subcutaneously, three times per week. Eligible patients were aged 40–79 years, had been diagnosed in the past 48 months, had a forced vital capacity of 55–90% of the predicted value, and a haemoglobin-corrected carbon monoxide diffusing capacity of 35–90% of the predicted value. The primary endpoint was overall survival time from randomisation measured at the second interim analysis, when the proportion of deaths had reached 75% of those expected by the study conclusion. This study is registered with ClinicalTrials.gov, number NCT00075998. Findings At the second interim analysis, the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo (1·15, 95% CI 0·77–1·71, p=0·497), and indicated that the study should be stopped. After a median duration of 64 weeks (IQR 41–84) on treatment, 80 (15%) patients on interferon gamma-1b and 35 (13%) on placebo had died. Almost all patients reported at least one adverse event, and more patients on interferon gamma-1b group had constitutional signs and symptoms (influenza-like illness, fatigue, fever, and chills) than did those on placebo. Occurrence of serious adverse events (eg, pneumonia, respiratory failure) was similar for both treatment groups. Treatment adherence was good and few patients discontinued treatment prematurely in either group. Interpretation We cannot recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis, which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function. Funding InterMune.

Published
2009

6. Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial

Author

Sheela Sitaraman, Richard Roxburgh, Kristina Gutschmidt, Ela Stefanescu, Drago Bratkovic, Thomas Burrow, Kornblum Cornelia, Kristl Claeys, Miriam Freimer, Ozlem Goker-Alpan, Srilakshmi Kuchipudi, Alan Pestronk, Wolfgang Löscher, Francoise Bouhour, Maria Judit Molnar, Ans T. van der Ploeg, Halina Bartosik-Psujek, Mitchell Goldman, Robert D. Henderson, Stephanie Dearmey, Colin Quinn, Paula R. Clemens, Priya S. Kishnani, Jennifer B Avelar, Nicola Longo, Shahram Attarian, Robert Hopkin, Tomo Sawada, Blaž Koritnik, George Konstantinos Papadimas, Hideaki Shiraishi, Christopher Lindberg, Jin-Hong Shin, Ivaylo Tarnev, Tahseen Mozaffar, Heather Lau, Michel Tchan, Jozsef Janszky, Tobias Ruck, Sabrina Sacconi, Benedikt Schoser, Hashiguchi Akihiro, Patrick Deegan, Ernest Butler, Nuria Vidal-Fernandez, Antonio Toscano, Tarekegn Hiwot, Gee Kim, Emmanuelle Salort-Campana, Jeff Castelli, Pascal Laforet, Céline Tard, Crystal Eldridge, Aneal Khan, Stephan Wenninger, Simona Fecarotta, Jordi Díaz-Manera, Jorge Alonso-Pérez, Yin-Hsiu Chien, Mark Tarnopolsky, Olimpia Musumeci, Hiroshi Kobayashi, Helio Pedro, Jonathan Cauci, Agnes Sebok, Cynthia Bodkin, Hai Jiang, Julie Berthy, Vescei Laszlo, Derralynn Hughes, David Reyes-Leiva, Aleksandra Dominovic-Kovacevic, Mazen M. Dimachkie, Hernan Amartino, Hani Kushlaf, Barry J. Byrne, Giancarlo Parenti, Henning Andersen, Mark Roberts, Marie Wencel, Jaime Vengoechea, Schoser, B., Roberts, M., Byrne, B. J., Sitaraman, S., Jiang, H., Laforet, P., Toscano, A., Castelli, J., Diaz-Manera, J., Goldman, M., van der Ploeg, A. T., Bratkovic, D., Kuchipudi, S., Mozaffar, T., Kishnani, P. S., Sebok, A., Pestronk, A., Dominovic-Kovacevic, A., Khan, A., Koritnik, B., Tard, C., Lindberg, C., Quinn, C., Eldridge, C., Bodkin, C., Reyes-Leiva, D., Hughes, D., Stefanescu, E., SALORT-CAMPANA, E., Butler, E., Bouhour, F., Kim, G., Konstantinos Papadimas, G., Parenti, G., Bartosik-Psujek, H., Kushlaf, H., Akihiro, H., Lau, H., Pedro, H., Andersen, H., Amartino, H., Shiraishi, H., Kobayashi, H., Tarnev, I., Vengoechea, J., Avelar, J., Shin, J. -H., Cauci, J., Alonso-Perez, J., Janszky, J., Berthy, J., Cornelia, K., Gutschmidt, K., Claeys, K., Judit Molnar, M., Wencel, M., Tarnopolsky, M., Dimachkie, M., Tchan, M., Freimer, M., Longo, N., Vidal-Fernandez, N., Musumeci, O., Goker-Alpan, O., Deegan, P., Clemens, P. R., Roxburgh, R., Henderson, R., Hopkin, R., Sacconi, S., Fecarotta, S., Attarian, S., Wenninger, S., Dearmey, S., Hiwot, T., Burrow, T., Ruck, T., Sawada, T., Laszlo, V., Loscher, W., Chien, Y. -H., and Pediatrics

Subjects
education.field_of_study, medicine.medical_specialty, 1-Deoxynojirimycin, Adolescent, Glycogen Storage Disease Type II, business.industry, Population, alpha-Glucosidases, Enzyme replacement therapy, Placebo, Treatment Outcome, Double-Blind Method, SDG 3 - Good Health and Well-being, Internal medicine, Miglustat, medicine, Clinical endpoint, Humans, Respiratory function, Neurology (clinical), Adverse effect, education, business, Alglucosidase alfa, medicine.drug
Abstract

Summary Background Pompe disease is a rare disorder characterised by progressive loss of muscle and respiratory function due to acid α-glucosidase deficiency. Enzyme replacement therapy with recombinant human acid α-glucosidase, alglucosidase alfa, is the first approved treatment for the disease, but some patients do not respond, and many do not show a sustained benefit. We aimed to assess the safety and efficacy of an investigational two-component therapy (cipaglucosidase alfa, a novel recombinant human acid α-glucosidase, plus miglustat, an enzyme stabiliser) for late-onset Pompe disease. Methods We did a randomised, double-blind, parallel-group, phase 3 trial at 62 neuromuscular and metabolic medical centres in 24 countries in the Americas, Asia-Pacific, and Europe. Eligible participants were aged 18 years or older with late-onset Pompe disease, and had either been receiving alglucosidase alfa for at least 2 years or were enzyme replacement therapy-naive. Participants were randomly assigned (2:1) using interactive response technology software, stratified by 6-min walk distance and previous enzyme replacement therapy status, to intravenous cipaglucosidase alfa (20 mg/kg) plus oral miglustat or to intravenous alglucosidase alfa (20 mg/kg) plus oral placebo once every 2 weeks for 52 weeks. Patients, investigators, and outcome assessors were masked to treatment assignment. The primary endpoint was change from baseline to week 52 in 6-min walk distance, assessed using a mixed-effect model for repeated measures analysis for comparison of superiority in the intention-to-treat population (all patients who received at least one dose of study drug). This study is now complete and is registered with ClinicalTrials.gov , NCT03729362 . Findings Between Dec 3, 2018, and Nov 26, 2019, 130 patients were screened for eligibility and 125 were enrolled and randomly assigned to receive cipaglucosidase alfa plus miglustat (n=85) or alglucosidase alfa plus placebo (n=40). Two patients in the alglucosidase alfa plus placebo group did not receive any dose due to absence of genotype confirmation of late-onset Pompe disease and were excluded from analysis. Six patients discontinued (one in the alglucosidase alfa plus placebo group, five in the cipaglucosidase alfa plus miglustat group), and 117 completed the study. At week 52, mean change from baseline in 6-min walk distance was 20·8 m (SE 4·6) in the cipaglucosidase alfa plus miglustat group versus 7·2 m (6·6) in the alglucosidase alfa plus placebo group using last observation carried forward (between-group difference 13·6 m [95% CI −2·8 to 29·9]). 118 (96%) of 123 patients experienced at least one treatment-emergent adverse event during the study; the incidence was similar between the cipaglucosidase alfa plus miglustat group (n=81 [95%]) and the alglucosidase alfa plus placebo group (n=37 [97%]). The most frequently reported treatment-emergent adverse events were fall (25 [29%] patients in the cipaglucosidase alfa plus miglustat group vs 15 [39%] in the alglucosidase alfa plus placebo group), headache (20 [24%] vs 9 [24%]), nasopharyngitis (19 [22%] vs 3 [8%]), myalgia (14 [16%] vs 5 [13%]), and arthralgia (13 [15%]) vs 5 [13%]). 12 serious adverse events occurred in eight patients in the cipaglucosidase alfa plus miglustat group; only one event (anaphylaxis) was deemed related to study drug. One serious adverse event (stroke) occurred in the alglucosidase alfa plus placebo group, which was deemed unrelated to study drug. There were no deaths. Interpretation Cipaglucosidase alfa plus miglustat did not achieve statistical superiority to alglucosidase alfa plus placebo for improving 6-min walk distance in our overall population of patients with late-onset Pompe disease. Further studies should investigate the longer-term safety and efficacy of cipaglucosidase alfa plus miglustat and whether this investigational two-component therapy might provide benefits, particularly in respiratory function and in patients who have been receiving enzyme replacement therapy for more than 2 years, as suggested by our secondary and subgroup analyses. Funding Amicus Therapeutics.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results