Stroke: Which Clot Buster Drug Works Best? Interview with:

A/Prof Bruce Campbell MBBS(Hons), BMedSc, PhD, FRACP

Dr. Campbell

A/Prof Bruce Campbell MBBS(Hons), BMedSc, PhD, FRACP
Consultant Neurologist, Head of Stroke
Department of Neurology, Royal Melbourne Hospital
Principal Research Fellow,Melbourne Brain Centre @ RMH
Department of Medicine
University of Melbourne Australia What is the background for this study? What are the main findings? 

Response: Patients with stroke due to a large blood vessel in the brain receive a clot-dissolving medication followed by clot retrieval surgery performed via an angiogram. The standard clot dissolving medication “alteplase” rarely opens the artery prior to clot retrieval surgery. Tenecteplase is genetically modified form of alteplase that may be more effective and is widely available (it is the standard clot dissolving medication used for heart attacks). It can be given over 10 seconds instead of the 1 hour required to infuse alteplase, meaning that patients can be transferred between hospitals to receive treatment more easily. Tenecteplase is also less expensive than alteplase.

In EXTEND-IA TNK we found that tenecteplase doubles the number of patients who have blood flow restored to the brain earlier than is possible with clot retrieval surgery (22% vs 10%) and improves patient outcomes compared to the current standard medication called alteplase.

1 in 5 tenecteplase treated patients have blood flow rapidly restored and do not require clot retrieval surgery compared to 1 in 10 with alteplase. What should readers take away from your report?

Response: Tenecteplase is likely to become the preferred medication for clot-dissolving in stroke patients who need clot retrieval surgery. The trial is likely to change stroke treatment guidelines and clinical practice. The improved effectiveness demonstrated in EXTEND-IA TNK, combined with increased convenience and reduced cost, make tenecteplase an attractive option for stroke patients who need clot retrieval surgery. What recommendations do you have for future research as a result of this work? 

Response: It is crucial that we complete ongoing phase 3 studies in non-thrombectomy patients – TASTE and ATTEST-2 – to determine the effect of tenecteplase more broadly in stroke patients. We are also performing a trial comparing the higher 0.40mg/kg tenecteplase dose used in the NOR-TEST prior to thrombectomy as patients with large vessel occlusion due to bigger clots may have the most to gain from an increased dose. Is there anything else you would like to add? 

Response: EXTEND-IA TNK was funded by the Australian Government National Health and Medical Research Council, National Heart Foundation, Stroke Foundation of Australia and Medtronic. There was no funding from Boehringer Ingelheim or Genentech who make both alteplase and tenecteplase.


Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke 

Bruce C.V. Campbell, Ph.D., Peter J. Mitchell, M.Med., Leonid Churilov, Ph.D., Nawaf Yassi, Ph.D., Timothy J. Kleinig, Ph.D., Richard J. Dowling, M.B., B.S., Bernard Yan, M.B., B.S., Steven J. Bush, M.B., B.S., Helen M. Dewey, M.D., Vincent Thijs, M.D., RebeccaScroop, M.B., B.S., Marion Simpson, M.B., B.S.,  for the EXTEND-IA TNK Investigators*

April 26, 2018 N Engl J Med 2018; 378:1573-1582
DOI: 10.1056/NEJMoa1716405

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Last Updated on April 30, 2018 by Marie Benz MD FAAD