Background/Aims: International consensus statements have recommended recovery trials focus on a targeted subgroup (e.g., severe weakness), index biomarkers of recovery potential (e.g., motor evoked potential, MEP), start early post-stroke (e.g., 3days) and deliver high-dose therapy throughout the heightened recovery potential window (i.e., 3months), however no trial has implemented all these recommendations. Our aim was to determine if high-dose upper limb therapy in the first 6months post-stroke in people with severe upper limb weakness shows promise, feasibility, and safety.
Methods: Prospective, multicentre Phase IIa adaptive Simon’s 2-stage trial. Eligible patients were 3-10days post-stroke with a Shoulder Abduction and Finger Extension (SAFE) score of 1-4. Participants were stratified based on MEP+/MEP- and randomly allocated to high-dose (100hours) therapy starting EARLY (≤10days) or LATE (@3months) post-stroke. Blinded assessment occurred ≤10days/3months/6months post-stroke. If the observed rate of ‘good outcomes’ at interim analysis (n=4/group) met the threshold to continue, up to n=9/group would be recruited (Power≥0.8).
Results: Eight participants (baseline: median 74years; 1male:7female; median 14/66 Fugl Meyer Upper Limb; 4MEP+:4MEP-) were recruited. High-dose therapy without serious safety events was feasible. At interim, the LATE group closed due to futility, while the EARLY group met the threshold to continue. However, this trial was closed due to limited hospital admissions screened to be SAFE eligible (~10%).
Conclusion: Only high-dose therapy met the threshold to continue in people with early and severe upper limb weakness. More effective strategies are required to enhance recruitment to early motor training trials to expand the evidence-base for treatments for this subpopulation.