Vol. 284 No. 15, October 18, 2000
Pramipexole vs Levodopa as Initial Treatment for Parkinson Disease
A Randomized Controlled Trial
Parkinson Study Group
Context: Pramipexole and levodopa both ameliorate the motor symptoms of
early Parkinson disease (PD), but no controlled studies have compared
long-term outcomes after initiating dopaminergic therapy with pramipexole
vs levodopa.
Objective: To compare the development of dopaminergic motor complications
after initial treatment of early PD with pramipexole vs levodopa.
Design: Multicenter, parallel-group, double-blind, randomized controlled
trial.
Setting: Academic movement disorders clinics at 22 sites in the United
States and Canada.
Patients: 301 patients with early PD who required dopaminergic therapy to
treat emerging disability, enrolled between October 1996 and August 1997.
Interventions: Subjects were randomly assigned to receive pramipexole, 0.5
mg 3 times per day, with levodopa placebo (n = 151); or carbidopa/levodopa,
25/100 mg 3 times per day, with pramipexole placebo (n = 150).
For patients with residual disability, the dosage was escalated during the
first 10 weeks.
From week 11 to month 23.5, investigators were permitted to add open-label
levodopa to treat continuing or emerging disability.
Main Outcome Measures: Time to the first occurrence of any of 3
dopaminergic complications: wearing off, dyskinesias, or on-off motor
fluctuations; changes in scores on the Unified Parkinson's Disease Rating
Scale (UPDRS), assessed at baseline and follow-up evaluations; and, in a
subgroup of 82 subjects evaluated at baseline and 23.5 months, ratio of
specific to nondisplaceable striatal iodine 123 2-- carboxymethoxy-3--
(4-iodophenyl)tropane (-CIT) uptake on single photon emission computed
tomography imaging of the dopamine transporter.
Results: Initial pramipexole treatment resulted in significantly less
development of wearing off, dyskinesias, or on-off motor fluctuations (28%)
compared with levodopa (51%) (hazard ratio, 0.45; 95% confidence interval
[CI], 0.30-0.66; P<.001).
The mean improvement in total UPDRS score from baseline to 23.5 months was
greater in the levodopa group than in the pramipexole group (9.2 vs 4.5
points; P<.001).
Somnolence was more common in pramipexole-treated patients than in
levodopa-treated patients (32.4% vs 17.3%; P = .003), and the difference
was seen during the escalation phase of treatment.
In the subgroup study, patients treated initially with pramipexole (n = 39)
showed a mean (SD) decline of 20.0% (14.2%) in striatal -CIT uptake
compared with a 24.8% (14.4%) decline in subjects treated initially with
levodopa (n = 39; P = .15).
Conclusions: Fewer patients receiving initial treatment for PD with
pramipexole developed dopaminergic motor complications than with levodopa
therapy.
Despite supplementation with open-label levodopa in both groups, the
levodopa-treated group had a greater improvement in total UPDRS compared
with the pramipexole group.
JAMA. 2000;284:1931-1938
Author/Article Information
Corresponding Author and Reprints:
Robert Holloway, MD, MPH,
Department of Neurology, University of Rochester, Rochester, New York,
14620 USA
(e-mail: [log in to unmask]).
Parkinson Study Group Investigators: Steering Committee:
Robert Holloway, MD, MPH, medical director,
Ira Shoulson, MD, principal investigator,
Karl Kieburtz, MD, MPH,
Michael McDermott, PhD, chief biostatistician,
Pierre Tariot, chair, safety monitoring committee,
Cornelia Kamp, MBA, project coordinator,
Denni Day, RN, MSPH, administrative manager,
Aileen Shinaman, JD, PSG executive director,
University of Rochester, Rochester, New York, USA;
Stanley Fahn, MD, coprincipal investigator,
Columbia University, New York, New York, USA;
Anthony Lang, MD,
Toronto Western Hospital, Toronto, Ontario, Canada;
Kenneth Marek, MD, principal investigator,
John Seibyl, MD, coprincipal investigator for -CIT,
Yale University School of Medicine, New Haven, Connecticut USA;
William Weiner, MD, Mickie Welsh, RN, DNS, ex-officio,
University of Southern California, Los Angeles, California USA.
Participating Investigators and Coordinators:
Rajesh Pahwa, MD,
Shantelle Coe, RN,
University of Kansas Medical Center, Kansas City, Missouri USA;
Lynn Barclay, MD,
Laura Sutherland, RN,
Kathy Hildebrand, RN,
Ottawa Civic Hospital, Ottawa, Ontario, Canada;
Jean Hubble, MD,
Carolyn Weeks, MT,
Ohio State University, Columbus, Ohio, USA;
Peter LeWitt, MD,
Clinical Neuroscience Center, Southfield, Michigan USA;
Janis Miyasaki, MD,
Jan Duff, RN,
Elspeth Sime, RN,
Toronto Western Hospital, Toronto, Ontario, Canada;
Oksana Suchowersky, MD,
University of Calgary Medical Clinic, Calgary, Alberta, Canada;
Mark Stacy, MD,
Matthias Kurth, MD,
Melanie Brewer, RN,
Mary Harrigan, RN, MN,
Barrow Neurological Institute, Phoenix, Arizona, USA;
David S. Russell, MD, PhD,
Barbara Fussell, RN,
Yale University School of Medicine, New Haven, Connecticut, USA;
Blair Ford, MD,
Sandra Dillon, RN,
Columbia University, New York, New York, USA;
John Hammerstad, MD,
Claudia Stone, RA,
Oregon Health Sciences University, Portland, Oregon, USA;
David Riley, MD,
Pamela Rainey, RN,
University Hospitals of Cleveland, Cleveland, Ohio, USA;
David Standaert, MD,
Marsha Tennis, RN,
Massachusetts General Hospital, Boston, Massachusetts, USA;
Frederick Wooten, MD,
Elke Rost-Ruffner, RN,
University of Virginia Health Sciences Center, Charlottesville, Virginia,
USA;
Stewart Factor, DO,
Diane Brown, RN,
Albany Medical College, Albany, New York, New York, USA;
Joseph Jankovic, MD,
Farah Atassi, MPH,
Baylor College of Medicine, Houston, Tex;
Roger Kurlan, MD,
Irenita Gardiner, RN,
University of Rochester, Rochester, New York, New York, USA;
Michel Panisset, MD,
Donna Amyot, RN,
Jean Hall, RN,
McGill Centre for Studies in Aging, Verdun, Quebec, Canada;
Ali Rajput, MD,
Theresa Shirley, RN,
Royal University Hospital, Saskatoon, Saskatchewan, Canada;
Robert Rodnitzky, MD, and
Judith Dobson, RN,
University of Iowa Hospitals, Iowa City, Iowa, USA;
Cliff Shults, MD,
Deborah Fontaine, RNC,
University of California, San Diego,
and the Alzheimer's Research Center, La Jolla, California, USA;
Cheryl Waters, MD,
Mickie Welsh, RN, DNSc,
Suzanne Schuman, RNC, MPA,
University of Southern California, Los Angeles, California, USA;
Ronald Pfeiffer, MD,
Sarah Rast, RN,
Brenda Pfeiffer, RN, BSN,
University of Tennessee, Memphis, Tennessee, USA.
Biostatistics and Clinical Trials Coordination Center Staff:
Alicia Brocht, BS,
Cindy Casaceli, MBA,
Susan Daigneault,
Karen Hodgeman,
Kathy Honsinger, MS,
Carolynn O'Connell,
Arthur Watts, BS,
University of Rochester, Rochester, New York, New York, USA;
Financial Disclosure: In keeping with the Parkinson Study Group conflict of
interest guidelines, none of the investigators have any personal financial
relationship with the sponsor.
All compensation received by investigators for trial-related services was
paid through a contract between the University of Rochester and the sponsor
that was established before the trial began.
Funding/Support: This work was supported primarily by the Pharmacia Corp.
Support was also provided by the National Parkinson Foundation Center of
Excellence to the Parkinson Study Group, and by the National Institutes of
Health for Clinical Research Center grants RR00044 and RR01066 to the
University of Rochester and Massachusetts General Hospital, respectively.
Acknowledgment: We thank the patients and their families who participated
in this study. We also thank the Safety Monitoring Committee:
W. Jackson Hall, PhD,
Pierre Tariot, MD, chair, University of Rochester, New York, USA;
Carl M. Leventhal, MD, Rockville, Maryland, USA;
Stephen Reich, MD, Johns Hopkins, Baltimore, Maryland, USA.
Contributions from the following individuals of the Pharmacia Corp are
gratefully acknowledged:
Leona Borchert MD, MPH,
Mark Corrigan, MD,
Baltazar Gomez-Mancilla, MD,
Bruno Musch MD,
Rhonda Ragual, MS,
Clayton Rowland, PhD,
Gene Wright, PhD,
Kalamazoo, Michigan, USA.
2000 American Medical Association. All rights reserved.
http://jama.ama-assn.org/issues/v284n15/abs/joc01004.html
janet paterson
53 now / 44 dx cd / 43 onset cd / 41 dx pd / 37 onset pd
TEL: 613 256 8340 URL: http://www.geocities.com/janet313/
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