RE-OPEN: Randomised trial of biosimilar TNK versus TPA during endovascular therapy for acute ischaemic stroke due to large vessel occlusions.

Rationale: Rapid and timely treatment with intravenous thrombolysis and endovascular treatment (EVT) in patients with acute ischaemic stroke (AIS) and large vessel occlusion (LVO) significantly improves patient outcomes. Bridging therapy is the current standard of care in these patients. However, an incompletely answered question is whether one thrombolytic agent is better than another during bridging therapy. Aim: The current study aims to understand if one thrombolytic agent is superior to the other during bridging therapy in the treatment of AIS and LVO. Sample size estimates: Using 80% power and an alpha error of 5 %, presuming a 10% drop out rate, a total of 372 patients will be recruited for the study. Methods and design: This study is a prospective, randomised, multicentre, open-label trial with blinded outcome analysis design. Study outcomes: The primary outcomes include proportion of patients who will be independent at 3 months (modified Rankin score (mRS) ≤2 as good outcome) and proportion of patients who achieve recanalisation modified thrombolysis in cerebral infarction grade 2b/3 at first angiography run at the end of EVT. Secondary outcomes include proportion of patients with early neurological improvement, rate of symptomatic intracerebral haemorrhage (ICH), rate of any ICH, rate of any systemic major or minor bleeding and duration of hospital stay. Safety outcomes include any intracranial bleeding or symptomatic ICH. Discussion: This trial is envisioned to confirm the theoretical advantages and increase the strength and quality of evidence for use of tenecteplase (TNK) in practice. Also, it will help to generate data on the efficacy and safety of biosimilar TNK. Trial registration number: CTRI/2022/01/039473.

Stroke and thrombolysis in developing countries.

BACKGROUND: Over the past few decades, the burden of stroke in developing countries has grown to epidemic proportions. Two-thirds of global stroke occurs in low- and middle-income countries. We have found that little information is obtainable concerning the availability of thrombolysis therapy in developing countries. SUMMARY OF REVIEW: The epidemiology of stroke is well investigated in the developed world; however, in the developing world stroke is less well documented. Most of the available stroke data from these countries are hospital-based. Stroke thrombolysis is currently used in few developing countries like Brazil, Argentina, Senegal, Iran, Pakistan, China, Thailand, and India. The two main barriers for implementation of thrombolysis therapy in developing countries are the high cost of tissue plasminogen activator and lack of proper infrastructure. Most of the centers with the infrastructure to deliver thrombolysis for stroke are predominantly private sector, and only available in urban areas. CONCLUSION: Until a more cost-effective thrombolytic agent and the proper infrastructure for widespread use of thrombolysis therapy are available, developing nations should focus on primary and secondary stroke prevention strategies and the establishment of stroke units wherever possible. Such multi-faceted approaches will be more cost-effective for developing countries than the use of thrombolysis.