Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN): An Adaptive Dose-Response Study of UK-279,276 in Acute Ischemic Stroke

Stroke

Volumn 34, Issue 11, 2003, Pages 2543-2548

  Krams, Michael ^a,f   Lees, Kennedy R ^b   Hacke, Werner ^c   Grieve, Andrew P ^a   Orgogozo, Jean Marc ^d   Ford, Gary A ^e  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^b WESTERN INFIRMARY   (United Kingdom)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^d HÔPITAL PELLEGRIN   (France)

^e NEWCASTLE UNIVERSITY   (United Kingdom)

^f PFIZER INC   (United States)

Author keywords

Dose response relationship, drug; Neuroprotection; Neutrophils; Research design

Indexed keywords

C REACTIVE PROTEIN; CD11B ANTIGEN; NEUTROPHIL INHIBITORY FACTOR; PLACEBO; TISSUE PLASMINOGEN ACTIVATOR; UK 279276; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; BAYES THEOREM; BRAIN EDEMA; BRAIN HEMORRHAGE; CAUSE OF DEATH; CEREBROVASCULAR ACCIDENT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FOLLOW UP; HEART FAILURE; HUMAN; INFECTION; MAJOR CLINICAL STUDY; MALE; MORTALITY; NEUTROPHIL; PNEUMONIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL;

ACUTE DISEASE; ADULT; AGED; AGED, 80 AND OVER; ANTIGENS, CD11B; BAYES THEOREM; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; GLYCOPROTEINS; HUMANS; MALE; MEDICAL FUTILITY; MIDDLE AGED; NEUTROPHILS; RECOMBINANT PROTEINS; SEVERITY OF ILLNESS INDEX; TIME FACTORS; TISSUE PLASMINOGEN ACTIVATOR; TREATMENT OUTCOME;

EID: 0242694372     PISSN: 00392499     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.STR.0000092527.33910.89     Document Type: Article

References (14)

1. Becker KJ. Targeting the central nervous system inflammatory response in ischemic stroke. Curr Opin Neurol. 2001;14:349-353.
2. Barone FC, Parsons AA. Therapeutic potential of anti-inflammatory drugs in focal stroke. Expert Opin Investig Drugs. 2000;9:2281-2306.
3. Emerich DF, Dean RL III, Bartus RT. The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct? Exp Neurol. 2002;173:168-181.
4. Enlimomab Acute Stroke Trial Investigators. Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial. Neurology. 2001;57:1428-1434.
5. Becker KJ. Anti-leukocyte antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in acute stroke. Curr Med Res Opin. 2002;18(suppl 2):s18-s22.
6. Jiang N, Chopp M, Chahwala S. Neutrophil inhibitory factor treatment of focal cerebral ischemia in the rat. Brain Res. 1998;788:25-34.
7. Zhang L, Zhang ZG, Zhang RL, Lu M, Krams M, Chopp M. Effects of a selective CD11b/CD18 antagonist and recombinant tissue plasminogen activator treatment alone and in combination in a rat embolic model of stroke. Stroke. 2003;34:1790-1795.
8. Lees KR, Diener H-C, Asplund K, Krams M, for the UK-279,276-301 Study Investigators. UK-279,276, a neutrophil inhibitory glycoprotein, in acute stroke: tolerability and pharmacokinetics. Stroke. 2003;34: 1704-1709.
9. Berry DA, Mueller P, Grieve AP, Smith MK, Parke T, Krams M. Bayesian designs for dose-ranging drug trials. In: Gatsonis C, Kass RE, Carlin B, Carriquiry A, Gelman A, Verdinelli I, West M, eds. Case Studies in Bayesian Statistics, Vol 5. New York, NY: Springer-Verlag; 2002:99-181.
10. European Stroke Initiative recommendations for stroke management. Cerebrovasc Dis. 2000;10:335-351.
11. West M, Harrison PJ. Bayesian Forecasting and Dynamic Models. New York, NY: Springer-Verlag: 1997.
12. Jorgensen HS, Nakayama H, Raaschou HO, Vive-Larsen J, Stoier M, Olsen TS. Outcome and time course of recovery in stroke: the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1995;76:399-412.
13. Schellinger PD, Fiebach JB. Hacke W. Imaging-based decision making in thrombolytic therapy for ischemic stroke: present status. Stroke. 2003;34: 575-583.
14. Alexandrov AV, Demchuk AM, Burgin WS. Insonation method and diagnostic flow signatures for transcranial power motion (M-mode) Doppler. J Neuroimaging. 2002;12:236-244.