Verschuur CVM, et al. - Researchers performed this multicenter, double-blind, placebo-controlled, delayed-start trial to determine a disease-modifying effect of levodopa in Parkinson's Disease. Outcomes revealed no disease-modifying effect of treatment with levodopa in combination with carbidopa among patients with early Parkinson’s disease who were evaluated over the course of 80 weeks.

• Patients with early Parkinson’s disease were randomly assigned to receive levodopa (100 mg three times per day) in combination with carbidopa (25 mg three times per day) for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa in combination with carbidopa for 40 weeks (delayed-start group).
• The between-group difference in the mean change from baseline to week 80 in the total score on the Unified Parkinson’s Disease Rating Scale (UPDRS; scores range from 0 to 176, with higher scores signifying more severe disease) was assessed as the primary outcome.
• The progression of symptoms, as measured by the UPDRS score, between weeks 4 and 40 and the noninferiority of early initiation of treatment to delayed initiation between weeks 44 and 80, with a noninferiority margin of 0.055 points per week were included in secondary analyses.

• Researchers randomly assigned a total of 445 patients: 222 to the early-start group and 223 to the delayed-start group.
• At baseline, the early-start group had the mean (±SD) UPDRS score of 28.1±11.4 points and the delayed-start group had 29.3±12.1 points.
• From baseline to week 80, change in UPDRS score was −1.0±13.1 points and −2.0±13.0 points, respectively (difference, 1.0 point; 95% confidence interval [CI], −1.5 to 3.5; P=0.44); this finding of no significant between-group difference at week 80 implies that levodopa had no disease-modifying effect.
• Based on UPDRS points measured per week, rate of progression of symptoms in the early-start group was 0.04±0.23 and in the delayed-start group was 0.06±0.34 between weeks 4 and 40 (difference, −0.02; 95% CI, −0.07 to 0.03).
• Between weeks 44 and 80, the corresponding rates of 0.10±0.25 and 0.03±0.28 were noted (difference, 0.07; two-sided 90% CI, 0.03 to 0.10); the difference in the rate of progression between weeks 44 and 80 did not meet the criterion for noninferiority of early receipt of levodopa to delayed receipt.
• The two groups displayed no significant difference in the rates of dyskinesia and levodopa-related fluctuations in motor response.