ENSAYOS CLÍNICOS

ANTI-PLATELET USEFUL DOSE STUDY

ESTUDIO APLAUD

Coordinator

E. Topol (Study Chairman)

Contact : Robert A. Harrington, MD, Duke Clinical Research Institute, Durham, NC harri019@mc.duke.edu

Sponsor

SmithKline Beecham

Status

Trial complete; results presented 11/98 and published 8/2000. Phase III trial (BRAVO) started 1999, terminated 12/00 by SmithKline Beecham due to lack of efficacy and safety concerns.

Intervention(s)

Lotrafiban

Oral platelet aggregation inhibitor; blocks platelet fibrinogen (glycoprotein IIB/IIIA integrin) receptor

Purpose

Phase II trial to assess the safety, tolerability, and pharmacokinetics of placebo or four doses of lotrafiban in combination with aspirin for secondary prevention in patients with cerebrovascular or cardiovascular disease.

Design

Study Design: Double-blind, randomized, controlled trial of 451 patients at 68 centers. Inclusion Criteria: Patients >18 years old were eligible if they had had a cardiovascular event (unstable angina or MI) within 42 days, TIA or minor ischemic stroke within 5 days to 6 months, or a major ischemic stroke within 30 days to 6 months before randomization.

Exclusion Criteria: National Institutes of Health Stroke Score of >=2, prior intracranial hemorrhage or aneurysm, severe comorbidities that limit life expectancy, major surgery or trauma <3 months before entry, planned surgery <4 months before entry, pregnancy, peptic ulcer <3 years before entry, low platelet count, renal insufficiency, hepatic dysfunction, abnormal prothrombin time, uncontrolled hypertension, treatment within the previous week with abciximab or within previous 24 hours with heparin or thrombolysis, aspirin allergy or intolerance, active drug or alcohol abuse within Patient Involvement: Patients received placebo or 5, 20, 50, or 100 mg lotrafiban, twice daily with 300 to 325 mg/d aspirin for 12 weeks. Primary Outcome: Incidence and tolerability of major and minor bleeding during treatment. Secondary Outcome(s): Inhibition of platelet aggregation and clinical events.

Results

The placebo and lotrafiban 5-mg groups had similarly low rates of minor and major bleeding, but the 100-mg arm was terminated early because of excess major bleeding. Protocol-defined thrombocytopenia occurred in 5 lotrafiban-treated patients (1.4%) and 1 placebo patient (1.1%), Lotrafiban produced dose-dependent inhibition of platelet aggregation; 5 mg lotrafiban did not differ significantly from placebo, whereas 100 mg inhibited aggregation by nearly 100%.

Publications and Web Links

Web

SmithKline Beecham Web Site

Article

Dose-finding, safety, and tolerability study of an oral platelet glycoprotein IIb/IIIa inhibitor, lotrafiban, in patients with coronary or cerebral atherosclerotic disease. Circulation. 2000 Aug 15;102(7):728-35.

Updated: 19-Jan-01