Abstract | BACKGROUND: METHODS: Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30-79 years. We randomly assigned eligible patients (ratio 1:1), by a centralised, computerised randomisation schedule, to receive double-blind either placebo or pramipexole (1·5 mg a day) and followed them up for 15 months. At 9 months, or as early as 6 months if considered necessary, placebo recipients were assigned to pramipexole. In a neuroimaging substudy, striatal dopamine-transporter binding was assessed by SPECT. All patients, investigators, and independent raters were masked to study treatment. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson's disease rating scale (UPDRS). This trial is registered with ClinicalTrials.gov, number NCT00321854. FINDINGS: Of 535 patients, 261 were randomly assigned to receive pramipexole and 274 to receive placebo. At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed pramipexole (-0·4 points, 95% CI -2·2 to 1·4, p=0·65). 62 patients in the early pramipexole group and 61 patients in the delayed pramipexole group were included in the neuroimaging substudy, for which the adjusted mean 15-month change in striatal (123)I-FP-CIT binding was -15·1% (SE 2·1) for early and -14·6% (2·0) for delayed pramipexole (difference -0·5 percentage points, 95% CI -5·4 to 4·4, p=0·84). Overall, 180 (81%) of patients given early pramipexole and 179 (84%) patients given delayed pramipexole reported adverse events (most frequently nausea), and 22 (10%) patients in the early pramipexole group and 17 (8%) in the delayed pramipexole group had serious events, two of which ( hallucinations and orthostatic hypotension) were deemed related to study drug. INTERPRETATION: By clinical and neuroimaging measures, pramipexole showed little evidence differentiating 15-month usage from usage delayed for 6-9 months. The results do not support the hypothesis that pramipexole has disease-modifying effects. FUNDING: Boehringer Ingelheim GmbH.
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Authors | Anthony H V Schapira, Michael P McDermott, Paolo Barone, Cynthia L Comella, Stefan Albrecht, Helen H Hsu, Daniel H Massey, Yoshikuni Mizuno, Werner Poewe, Olivier Rascol, Kenneth Marek |
Journal | The Lancet. Neurology
(Lancet Neurol)
Vol. 12
Issue 8
Pg. 747-55
(Aug 2013)
ISSN: 1474-4465 [Electronic] England |
PMID | 23726851
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antiparkinson Agents
- Benzothiazoles
- Pramipexole
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Topics |
- Adult
- Aged
- Analysis of Variance
- Antiparkinson Agents
(therapeutic use)
- Benzothiazoles
(therapeutic use)
- Double-Blind Method
- Drug Administration Schedule
- Female
- Humans
- Male
- Middle Aged
- Parkinson Disease
(diagnostic imaging, drug therapy, psychology)
- Pramipexole
- Quality of Life
- Retrospective Studies
- Severity of Illness Index
- Tomography, Emission-Computed, Single-Photon
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