Werner Poewe1, Klaus Seppi2, Cheryl J Fitzer-Attas3, Gregor K Wenning4, Sid Gilman5, Phillip A Low6, Nir Giladi7, Paolo Barone8, Cristina Sampaio9, Eli Eyal10, Olivier Rascol11. 1. Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: werner.poewe@i-med.ac.at. 2. Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. 3. Teva Pharmaceutical Industries, Petach Tikva, Israel; CHDI Foundation, Princeton, NJ, USA. 4. Division of Neurobiology, Innsbruck Medical University, Innsbruck, Austria. 5. Geddes Road, Ann Arbor, MI, USA. 6. Mayo Clinic, Department of Neurology, Rochester, MN, USA. 7. Sackler School of Medicine, Sagol School of Neuroscience, Tel-Aviv University Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel. 8. Università degli Studi di Salerno, Dipartimento di Medicina e Chirurgia, Via Giovanni Paolo II, Salerno, Italy. 9. CHDI Foundation, Princeton, NJ, USA. 10. Teva Pharmaceutical Industries, Petach Tikva, Israel. 11. Clinical Investigation Center CIC1436, Departments of Clinical Pharmacology and Neurosciences, INSERM and University Hospital of Toulouse, Faculty of Medicine, Toulouse, France.
Abstract
BACKGROUND: Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. METHODS: We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. FINDINGS: We randomly assigned 174 participants to the rasagiline group (n=84) or theplacebogroup (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). INTERPRETATION: In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. FUNDING: Teva Pharmaceutical Industries and H Lundbeck A/S.
RCT Entities:
BACKGROUND:Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. METHODS: We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. FINDINGS: We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). INTERPRETATION: In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. FUNDING: Teva Pharmaceutical Industries and H Lundbeck A/S.
Authors: Carlos E Mendoza-Santiesteban; Jose-Alberto Palma; Jose Martinez; Lucy Norcliffe-Kaufmann; Thomas R Hedges; Horacio Kaufmann Journal: Mov Disord Date: 2015-09-11 Impact factor: 10.338
Authors: Wolfgang Singer; Ann M Schmeichel; Mohammad Shahnawaz; James D Schmelzer; Bradley F Boeve; David M Sletten; Tonette L Gehrking; Jade A Gehrking; Anita D Olson; Rodolfo Savica; Mariana D Suarez; Claudio Soto; Phillip A Low Journal: Ann Neurol Date: 2020-08-01 Impact factor: 10.422