Journal Club Summary

Methodology: 3/5          
Usefulness: 3/5
Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O’Brien B, Bladin C, McElduff P, Allen C, Bateman G, Donnan G, Davis S, Levi C.
N Engl J Med. 2012 Mar 22;366(12):1099-107.
This was a randomized phase 2B trial comparing the efficacy of tenecteplase versus alteplase for acute ischemic stroke, which found better % reperfusion on CT and better NIHSS scores at 24 hours with high-dose tenecteplase (0.25 mg/kg). One criticism from the group was the lack of clinically meaningful primary outcomes. The results were impressive considering this was a phase 2B trial, and the consensus among the group is that it would be interesting to see what a phase 3 trial would show for tenecteplase as thrombolytic therapy for stroke. 
By: Dr. Krishan Yadav
(Presented November 2012)

Epi Lesson:  Phases of a clinical trial

Clinical trials involving new drugs are classified into four phases with Health Canada and the FDA generally requiring a drug to have passed through Phase 3 before general approval. Phase 1 trials test the treatment in a small group of healthy people (20-80) to evaluate its safety, dosage range, and side effects. Phase 2 trials give the treatment to patients and in larger numbers (100-300) to evaluate effectiveness and safety. Phase 3 trials give the treatment to large groups of paitents (1,000-3,000) to confirm its effectiveness, monitor side effects, and compare to commonly used treatments. Phase 4 trials are post-marketing studies to determine additional information about side effects and risks. [2a trials studies focus on proving the hypothesized mechanism of action while the larger 2b trials seek to determine the optimum dose] 

By: Dr. Ian Stiell