Trial of Deferiprone in Parkinson's Disease.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Devos David, Labreuche Julien, Rascol Olivier, Corvol Jean-Christophe, Duhamel Alain, Guyon Delannoy Pauline, Poewe Werner, Compta Yaroslau, Pavese Nicola, Růžička Evžen, Dušek Petr, Post Bart, Bloem Bastiaan R, Berg Daniela, Maetzler Walter, Otto Markus, Habert Marie-Odile, Lehericy Stéphane, Ferreira Joaquim, Dodel Richard, Tranchant Christine, Eusebio Alexandre, Thobois Stéphane, Marques Ana-Raquel, Meissner Wassilios G, Ory-Magne Fabienne, Walter Uwe, de Bie Rob M A, Gago Miguel, Vilas Dolores, Kulisevsky Jaime, Januario Cristina, Coelho Miguel V S, Behnke Stefanie, Worth Paul, Seppi Klaus, Ouk Thavarak, Potey Camille, Leclercq Céline, Viard Romain, Kuchcinski Gregory, Lopes Renaud, Pruvo Jean-Pierre, Pigny Pascal, Garçon Guillaume, Simonin Ophélie, Carpentier Jessica, Rolland Anne-Sophie, Nyholm Dag, Scherfler Christoph, Mangin Jean-François, Chupin Marie, Bordet Régis, Dexter David T, Fradette Caroline, Spino Michael, Tricta Fernando, Ayton Scott, Bush Ashley I, Devedjian Jean-Christophe, Duce James A, Cabantchik Ioav, Defebvre Luc, Deplanque Dominique, Moreau Caroline, FAIRPARK-II Study Group
Аннотация
METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.
RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.
CONCLUSIONS: In participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).