MedicalResearch.com Interview with:
Craig Anderson | MD PhD FRACP
Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney
Neurologist, Neurology Department, Royal Prince Alfred Hospital
The George Institute for Global Health at Peking University Health Science Center
Haidian District | Beijing, 100088 P.R. China
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There is much controversy over the benefits of a lower dose of intravenous alteplase, particularly in Asia, after the Japanese regulatory authorities approved a dose of 0.6 mg/kg 10 years ago compared to the US FDA and other regulatory authorities approving 0.9 mg/kg 20 years ago. The investigator inititiated and conducted ENCHANTED trial aimed to determine the effectiveness and safety of these two doses in an international multicentre pragmatic open design.
The main results did not confirm the low-dose to be statistically ‘non-inferior’ partly due to the primary outcome measure chosen and partly due to the statistical approach, but it did confirm that the lower dose was safer with less risk of the major complication of this treatment, that of major bleeding in the brain. However, it would appear that this safety effect was offset by some reduce efficacy in terms of functional recovery.
The aim of this secondary analysis of the trial data was to examine in more detail the differences between low and standard dose alteplase according to the participants’ age, ethnicity (Asian vs non-Asian) and severity of neurological deficit at the time of treatment. We did this because the popular belief is that a lower dose might be preferred in older people, and Asians, because of the potential for more likelihood of bleeding, and preferentially to use the standard dose in those with more severe strokes potentially due to greater ‘clot burden’ from a blocked artery to the brain.
The results showed that the main findings on the outcome of surviving free of disability were the same according to age, ethnicity and stroke severity – that is, there was no preferential dose in any of these groups. Similarly, the safety benefit of low dose alteplase on brain haemorrhage, did not clearly translate into clinical disability outcomes in any of the patient groups studied.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: Standard dose intravenous alteplase is the preferred treatment in all thrombolysis eligible patients with acute ischemic stroke, despite a clear apparent safety benefit of the low dose.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: More research, including analysis of the ENCHANTED dataset, is required to determine where the safety benefits of low dose alteplase can be applied in a targeted patient group for overall clinical benefit.
MedicalResearch.com: Is there anything else you would like to add?
Response: The second part to the ENCHANTED trial, that of whether more intensive blood pressure control in patients with acute ischemic stroke who receive alteplase, will be published in 2019.
I have accepted modest speaker fees and travel reimbursement from Boehringer Ingelheim, the owners of alteplase outside of the US.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Wang X, Robinson TG, Lee T, Li Q, Arima H, Bath PM, Billot L, Broderick J, Demchuk AM, Donnan G, Kim JS, Lavados P, Lindley RI, Martins SO, Olavarria VV, Pandian JD, Parsons MW, Pontes-Neto OM, Ricci S, Sharma VK, Thang NH, Wang J, Woodward M, Anderson CS, Chalmers J, for the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) Investigators. Low-Dose vs Standard-Dose Alteplase for Patients With Acute Ischemic StrokeSecondary Analysis of the ENCHANTED Randomized Clinical Trial. JAMA Neurol. Published online October 02, 2017. doi:10.1001/jamaneurol.2017.2286
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