Evidence Table TxCM 7What is the effectiveness of adding COMT inhibitors vs. placebo in the treatment of later Parkinson’s disease patients with motor complications?

Bibliographic referenceOlanow CW, Kieburtz K, Stern M, Watts R, Langston JW, Guarnieri M et al. Double-blind, placebo- controlled study of entacapone in levodopa-treated patients with stable Parkinson disease. Archives of Neurology 2004;61:1563–8.
Study typeRandomised, double-blind, placebo-controlled study
Evidence level
Study objectiveTo determine if the addition of entacapone administration provides benefit to levodopa-treated PD patients who have a stable response to levodopa and do no experience motor fluctuations.
Number of patientsN=750 PD patients
 N=373 entacapone
 N=377 placebo

Location: USA
Sites: 5?
Patient characteristicsInclusion criteria was based on: a good response to levodopa and at least 2 of the following: rigidity, resting tremor, and bradykinesia. Levodopa doses had to be stable for at least one month, with a maximum of four daily doses of the regular 3 daily does of controlled-release formulation. Participants could not experience end-of-dose wearing off with 4 hours of levodopa use.
EntacaponePlacebo
Mean age (y)69.8 ± 9.370.2 ± 9.4
Sex, % male72.968.7
Duration of PD, mean ± SD, y4.4 ± 3.54.5 ± 3.5
Duration of LD prescription, y3.6 ± 3.13.6 ± 3.3
LD dose, mean ± SD, mg401.3 ± 191.9406.2 ± 179.1
No significant differences between groups.
Intervention200 mg of entacapone
ComparisonPlacebo
Length of follow-up26 week trial duration
Outcome measuresUPDRS, LD dose, PDQ-39, SF-36, Parkinson’s symptom inventory (PSI), Global assessment
Effect size[arrowhead] No significant difference between groups for UPDRS scores
[arrowhead] Levodopa dose was reduced from baseline in entacapone compared to placebo (p=0.004)
[arrowhead] PDQ-39 ((out of 9 parameters) 3 were significant in favour of entacapone: total score (p<0.001), mobility (p=0.001) and ADL (p<0.001)
[arrowhead] SF-36 (out of 10 parameters) 3 were significant in favour of entacapone: physical functioning (p=0.047), vitality domain (p=0.04), physical component (p=0.009)
[arrowhead] PSI: (2 parameters) both significant: frequency (p=0.007) and distress (p=0.02)
[arrowhead] Global assessment was also significant in favour of entacapone: investigator improved (p=0.08) and subject improved (p=0.02)

Adverse events
[arrowhead] Nausea and dyskinesia were most common and more frequent in entacapone group
Source of fundingPharmaceutical
Additional comments[arrowhead] Methods of randomisation stated
[arrowhead] Power calculations provided
[arrowhead] Allocation concealment methods not stated
[arrowhead] LD dose could not be increased during study- only decreased
[arrowhead] Intention-to-treat analysis
[arrowhead] Number of sites not clearly stated
[arrowhead] Multi-centre analysis not provided
Citation
NCC CC ID (Ref Man)104

From: Evidence Tables

Cover of Parkinson's Disease
Parkinson's Disease: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 35.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2006, Royal College of Physicians of London.

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