Journal Club Summary
Methodology Score: 4/5
Usefulness Score: 2/5
Morelli A, et al. JAMA. 2013 Oct 23;310(16):1683-91
This single centre phase 2B trial randomized septic patients still requiring vasopressors after 24hrs of EGDT to esmolol infusions to a target hear rate of between 85-94 or standard sepsis therapy and found overall mortality at 28 days of 49.4% in the esmolol group and 80.5% in the control group representing an ARR of 31% and a NNT of 3.2. The group agreed that this study, although promising, demonstrated very high baseline mortality numbers, and that a large multicenter study is required to confirm effectiveness and safety of rate control.
By: Dr. Shawn Mondoux
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 patients (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