Biogen's Hirulog, Behringwerke AG's recombinant plasminogenactivator (RPA) and Burroughs Wellcome's RheothRx are beingconsidered for inclusion in an ISIS-5 trial.
The International Study of Infarct Survival (ISIS) steeringcommittee met in Nice, France, over Labor Day weekend toconsider the design of a future trial, anticipated for some timein early 1995. The trial will study the efficacy of variousinterventions in preventing mortality following myocardialinfarction (MI). Various possible interventions were proposedat the meeting but nothing has been finalized.
John Cairns, chairman of the Department of Medicine atMcMaster University in Hamilton, Ontario, and Canadiancoordinator of ISIS, told BioWorld that one proposal is to studya thrombin inhibitor, perhaps Hirulog -- in combination withaspirin vs. aspirin alone, or vs. aspirin and heparin -- to see ifthe drug has an added benefit in preventing mortality. Hirulogis a synthetic formulation of a substance found in the saliva ofleeches that has an anti-thrombin property that prevents bloodcoagulation.
Other interventions discussed by the committee include theantithrombotic compound RheothRx, which BurroughsWellcome licensed from CytRx Corp. in 1990; comparison ofstreptokinase and RPA, the latter of which is underdevelopment by Hoechst AG subsidiary Behringwerke and inclinicals in Germany and Europe; a glucose/insulin/heparincombination; and either conventional or newer beta blockers.Cairns said ISIS-5 will be a complex factorial design thatexamines a number of different interventions.
The ISIS network includes 1,000 hospitals in Europe, the U.S.and Canada that have contributed patients to the past four ISIStrials. The main ISIS office is at Oxford University, headed byPeter Sleight. The U.S. coordinator is Charles Hennekens ofBrigham and Women's Hospital in Boston.
Cairns said ISIS-5 will probably include 40,000 to 50,000patients. The study will measure the effect of the drug onmortality within 35 days, just as in the previous trials. He saidthat as long as there are questions about appropriate therapyfor myocardial infarction and financial support, there willcontinue to be a series of ISIS trials.
ISIS-1, conducted in the early 1980s illustrated the efficacy ofbeta blockers in improving mortality; ISIS-2 showed that bothstreptokinase and aspirin reduced mortality and that theywere more effective in combination; ISIS-3 compared the threemain thrombolytics, APSAC, tissue plasminogen activator (t-PA) and streptokinase, and concluded that streptokinase is aseffective and safer than the two other more expensive drugs;and ISIS-4 which studied the benefit of oral ace inhibitors, oralmononitrates and I.V. magnesium. The results of the last trialwill be presented at the American Heart Association's annualmeeting in Atlanta Nov. 7-11.
-- Brenda Sandburg News Editor
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