Controlled clinical trials with prothrombin complex concentrates.

Since the introduction of PCC for treatment of bleeding episodes in hemophiliacs with inhibitors in 1972, many anecdotal reports and uncontrolled observations have been published, often with conflicting reports of efficacy. To date, three controlled double blind studies have been completed in which PCC have been evaluated. In each of the three studies acute hemarthrosis has been the only (Lusher et al 1980; Lusher et al 1983) or the predominant (Sjamsoedin 1981) type of bleeding evaluated. While acute joint bleeding lends itself well to clinical trial, there are recognized problems in evaluating response to treatment. Despite these limitations, it is noteworthy that non-activated PCC were found to be effective in approximately 50% of episodes in all three trials. Future trials are now being planned in an attempt to determine the role of activated PCC in the management of bleeding episodes in hemophiliacs with inhibitors. In the design of these trials, possible modifications to be considered are the exclusion (or separate randomization) of chronically disabled or "target" joints, more than one dose of unknown product, and longer periods of assessment.