(Stroke. 1997;28:2347-2352.)
© 1997 American Heart Association, Inc.
Articles |
Treatment of Acute Ischemic Stroke With Piracetam
From the Department of Neurology, Middelheim Hospital and University of Antwerp, Belgium (P.P.D.D.), Department of Neurology, University Hospital, Ghent, Belgium (J.D.R.), Department of Clinical Research and Development, UCB Pharma, Braine-l'Alleud, Belgium (W.D.), Department of Genetic Epidemiology, University of Louvain, Belgium (R.V.), and Department of Neurology, Pellegrin Hospital, University of Bordeaux II, Bordeaux, France (J-M.O.).
Correspondence to Professor De Deyn, Department of Neurology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium. Reprint requests to B. Raoult, UCB Pharma, Chemin du Foriest, Building S3, 1420 Braine-l'Alleud, Belgium.
Background and Purpose Piracetam, a nootropic agent with neuroprotective properties, has been reported in pilot studies to increase compromised regional cerebral blood flow in patients with acute stroke and, given soon after onset, to improve clinical outcome. We performed a multicenter, randomized, double-blind trial to test whether piracetam conferred benefit when given within 12 hours of the onset of acute ischemic stroke to a large group of patients.
Methods Patients received placebo or 12 g piracetam as an initial intravenous bolus, 12 g daily for 4 weeks and 4.8 g daily for 8 weeks. The primary end point was neurologic outcome after 4 weeks as assessed by the Orgogozo scale. Functional status at 12 weeks as measured by the Barthel Index was the major secondary outcome. CT scan was performed within 24 hours of the onset of stroke but not necessarily before treatment. Analyses based on the intention to treat were performed in all randomized patients (n=927) and in an "early treatment" population specified in the protocol as treatment within 6 hours of the onset of stroke but subsequently redefined as less than 7 hours after onset (n=452).
Results In the total population, outcome was similar with both treatments (the mean Orgogozo scale after 4 weeks: piracetam 57.7, placebo 57.6; the mean Barthel Index after 12 weeks: piracetam 55.8, placebo 53.1). Mortality at 12 weeks was 23.9% (111/464) in the piracetam group and 19.2% (89/463) in the placebo group (relative risk 1.24, 95% confidence interval, 0.97 to 1.59; P=.15). Deaths were fewer in the piracetam group in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke. Post hoc analyses in the early treatment subgroup showed differences favoring piracetam relative to placebo in mean Orgogozo scale scores after 4 weeks (piracetam 60.4, placebo 54.9; P=.07) and Barthel Index scores at 12 weeks (piracetam 58.6, placebo 49.4; P=.02). Additional analyses within this subgroup, confined to 360 patients with moderate and severe stroke (initial Orgogozo scale score <55), showed significant improvement on piracetam in both outcomes (P<.02).
Conclusions Piracetam did not influence outcome when given within 12 hours of the onset of acute ischemic stroke. Post hoc analyses suggest that piracetam may confer benefit when given within 7 hours of onset, particularly in patients with stroke of moderate and severe degree. A randomized, placebo-controlled, multicenter study, the Piracetam Acute Stroke Study II (PASS II) will soon begin.
Key Words: cerebral ischemia • neuroprotection • clinical trials • piracetam
This article has been cited by other articles:
 |
|
 |
|
  H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, May 22, 2007; 115(20): e478 - e534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke, May 1, 2007; 38(5): 1655 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Niewada, M. Skowronska, D. Ryglewicz, B. Kaminski, A. Czlonkowska, and on behalf of the Polish National Stroke Prevention Acute Ischemic Stroke Care and Outcome in Centers Participating in the Polish National Stroke Prevention and Treatment Registry Stroke, July 1, 2006; 37(7): 1837 - 1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Elkins, T. Khatabi, L. Fung, J. Rootenberg, and S. C. Johnston Recruiting Subjects for Acute Stroke Trials: A Meta-Analysis Stroke, January 1, 2006; 37(1): 123 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Weaver, J. Leonardi-Bee, F. J. Bath-Hextall, and P. M.W. Bath Sample Size Calculations in Acute Stroke Trials: A Systematic Review of Their Reporting, Characteristics, and Relationship With Outcome Stroke, May 1, 2004; 35(5): 1216 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Evans, F. Harraf, N. Donaldson, and L. Kalra Randomized Controlled Study of Stroke Unit Care Versus Stroke Team Care in Different Stroke Subtypes Stroke, February 1, 2002; 33(2): 449 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Croom, N. J. Lobaugh, G. Koren, J. Rovet, and R. Haslam Piracetam Study: Poorly Designed and Misinterpreted Arch Pediatr Adolesc Med, October 1, 2001; 155(10): 1176 - 1178. [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Sacco, J. T. DeRosa, E. C. Haley Jr, B. Levin, P. Ordronneau, S. J. Phillips, T. Rundek, R. G. Snipes, J. L. P. Thompson, and for the GAIN Americas Investigators Glycine Antagonist in Neuroprotection for Patients With Acute Stroke: GAIN Americas: A Randomized Controlled Trial JAMA, April 4, 2001; 285(13): 1719 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Lobaugh, V. Karaskov, V. Rombough, J. Rovet, S. Bryson, R. Greenbaum, R. H. Haslam, and G. Koren Piracetam Therapy Does Not Enhance Cognitive Functioning in Children With Down Syndrome Arch Pediatr Adolesc Med, April 1, 2001; 155(4): 442 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Uchino, D. Billheimer, and S. C. Cramer Entry Criteria and Baseline Characteristics Predict Outcome in Acute Stroke Trials Stroke, April 1, 2001; 32(4): 909 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Samsa and D. B. Matchar Have Randomized Controlled Trials of Neuroprotective Drugs Been Underpowered? : An Illustration of Three Statistical Principles Stroke, March 1, 2001; 32(3): 669 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fisher and W. Schaebitz An Overview of Acute Stroke Therapy: Past, Present, and Future Arch Intern Med, November 27, 2000; 160(21): 3196 - 3206. [Full Text] [PDF]
|
|
|
|
|
|
J. Kessler, A. Thiel, H. Karbe, and W. D. Heiss Piracetam Improves Activated Blood Flow and Facilitates Rehabilitation of Poststroke Aphasic Patients Stroke, September 1, 2000; 31(9): 2112 - 2116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Duncan, H. S. Jorgensen, and D. T. Wade Outcome Measures in Acute Stroke Trials : A Systematic Review and Some Recommendations to Improve Practice Stroke, June 1, 2000; 31(6): 1429 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G DEVUYST and J BOGOUSSLAVSKY Recent progress in drug treatment for acute stroke J. Neurol. Neurosurg. Psychiatry, October 1, 1999; 67(4): 420 - 425. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Davis and D. Barer Neuroprotection in acute ischaemic stroke. II: Clinical potential Vascular Medicine, August 1, 1999; 4(3): 149 - 163. [Abstract] [PDF]
|
|
|
|
|
|
G. Sulter, C. Steen, and Jacques De Keyser Use of the Barthel Index and Modified Rankin Scale in Acute Stroke Trials Stroke, August 1, 1999; 30(8): 1538 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Njemanze, A. Chidi-Ebere, and J.-M. Orgogozo Three-Dimensional Vector Component Analysis of Neurological Stroke Scales • Response Stroke, August 1, 1999; 30(8): 1731 - 1733. [Full Text] [PDF]
|
|