Evidence map›Paper›PMID 30673543›Full record

Trial reportThe New England journal of medicine2019

Randomized Delayed-Start Trial of Levodopa in Parkinson's Disease.

Constant V M Verschuur, Sven R Suwijn, Judith A Boel, Bart Post, Bas R Bloem, Johannes J van Hilten, Teus van Laar, Gerrit Tissingh, Alexander G Munts, Guenther Deuschl and 5 more

Abstract readEquivalence TrialMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 6 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

155 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
  2. Guideline
  3. UsingInternational journal of molecular sciences · 2025
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Genome-Wide Association Studies of Cognitive and Motor Progression in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021
    Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Freezing of Gait: A Tribute to Nir Giladi.The European journal of neuroscience · 2026
    Article
  13. Article
  14. Article
  15. "Journal of Parkinson's disease · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Temporal evolution of antiparkinsonian drug prescription over 17 years: a real-world data analysis of Korean patients with Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  20. Article

95 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Constant V M VerschuurFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Sven R SuwijnFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Judith A BoelFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Bart PostFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Bas R BloemFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Johannes J van HiltenFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Teus van LaarFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Gerrit TissinghFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Alexander G MuntsFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Guenther DeuschlFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Anthony E LangFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Marcel G W DijkgraafFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Rob J de HaanFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
Rob M A de BieFrom the Department of Neurology, Amsterdam Neuroscience (C.V.M.V., S.R.S., J.A.B., R.M.A.B.), Clinical Epidemiology, Biostatistics, and Bioinformatics (M.G.W.D.), and the Clinical Research Unit (R.J.H.), Amsterdam UMC, University of Amsterdam, AMC, Amsterdam, the Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen (B.P., B.R.B.), the Department of Neurology, Leiden University Medical Center, Leiden (J.J.H.), the Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen (T.L.), the Department of Neurology, Zuyderland Medical Center, Heerlen (G.T.), and the Department of Neurology, Spaarne Gasthuis, Haarlem (A.G.M.) - all in the Netherlands; the Department of Neurology, University Medical Center Schleswig-Holstein, Kiel, Germany (G.D.); and the Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto (A.E.L.).
LEAP Study Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLevodopa is the main treatment for symptoms of Parkinson's disease. Determining whether levodopa also has a disease-modifying effect could provide guidance as to when in the course of the disease the treatment with this drug should be initiated.

methodsIn a multicenter, double-blind, placebo-controlled, delayed-start trial, we randomly assigned patients with early Parkinson's disease 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 primary outcome was 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). Secondary analyses included 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.

resultsA total of 445 patients were randomly assigned: 222 to the early-start group and 223 to the delayed-start group. The mean (±SD) UPDRS score at baseline was 28.1±11.4 points in the early-start group and 29.3±12.1 points in the delayed-start group. The change in UPDRS score from baseline to week 80 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. Between weeks 4 and 40, the rate of progression of symptoms, as measured in UPDRS points per week, was 0.04±0.23 in the early-start group and 0.06±0.34 in the delayed-start group (difference, -0.02; 95% CI, -0.07 to 0.03). The corresponding rates between weeks 44 and 80 were 0.10±0.25 and 0.03±0.28 (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 rates of dyskinesia and levodopa-related fluctuations in motor response did not differ significantly between the two groups.

conclusionsAmong patients with early Parkinson's disease who were evaluated over the course of 80 weeks, treatment with levodopa in combination with carbidopa had no disease-modifying effect. (Funded by the Netherlands Organization for Health Research and Development and others; LEAP Current Controlled Trials number, ISRCTN30518857 .).

Indexed as

AgedAntiparkinson AgentsCarbidopaDisease ProgressionDouble-Blind MethodDrug Administration ScheduleDrug Therapy, CombinationFemaleHumansLevodopaMaleMiddle AgedParkinson DiseaseTime-to-TreatmentAntiparkinson AgentsCarbidopaLevodopa

Identifiers

PMID30673543

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.