Wednesday, January 25, 2012

Helping TPA Help Patients Bleed

TPA for stroke, the miracle therapy that has your Emergency Department shoving people out of the way to drag someone to the CT scanner within 10 minutes of ED arrival, isn't good enough.  After all, TPA, a "clot-busting" drug that saves dying brain cells by restoring flow, only completely opens up the occluded target vessel within 2 hours in 20 to 30% of the cases, with partial recanalization occurring in up to 60%.  So, the "Texas Biotechnology Corporation" and their equity stakeholders at The University of Texas Health Science Center at Houston have undertaken a project to add additional anticoagulation - argatroban - to TPA in the interests of actually delivering on the "clot-busting" part of the promise.

This is an open-label, pilot safety study enrolling 65 patients.  It was stopped after the first 15 patients for safety review after two experienced intracranial hemorrhage.  After review, it was restarted with additional restrictions on only giving it to milder stroke patients with NIHSS score < 15 (right hemisphere) and < 20 (left hemisphere).  All patients subsequently underwent vascular imaging to assess for recanalization, and the authors reported safety outcomes for events within seven days.

The good news: sorry, no good news.  14 had sustained complete recanalization at 2 hours - 30%.  An additional 12 patients had sustained partial recanalization at 2 hours - 25%.  Of course, this isn't a controlled trial, so comparison to the recanalization rates demonstrated in existing literature is flawed - but it's certainly not an order of magnitude better.

But, this wasn't an efficacy trial, this was a safety trial.  And seven patients met the ultimate safety endpoint of death - 10%.  For intracranial hemorrhage, 19 (29%) patients had ICH, 3 of which were symptomatic. Because NIHSS score predicts bleeding, we can compare to the NINDS trial TPA group, whose median NIHSS score of 14 compared with this trial's median of 13.  The NINDS trial showed a 10.8% rate of ICH and about 4% mortality at 7 days.

Seems like a treatment with triple the ICH and double the mortality, and that isn't proven superior, shouldn't support the conclusion of "potentially safe" or that "Further study of this treatment combination appears warranted."

"The Argatroban and Tissue-Type Plasminogen Activator Stroke Study : Final Results of a Pilot Safety Study"

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