B-stars2: Early contralesional continuous theta burst stimulation (cTBS) to promote upper limb recovery after stroke - Rationale and design of a phase-3 multicentre, randomised, sham-controlled, clinical trial

RATIONALE: Many stroke survivors have persisting upper limb impairment. In a phase-2 trial, early contralesional continuous theta burst stimulation (cTBS) improved upper limb recovery and functional outcome after stroke, but confirmation of this benefit in a larger, phase-3 trial is required before this can be recommended as standard of care.

AIM: We aim to assess whether 10 sessions of cTBS of the contralesional primary motor cortex, combined with regular care upper limb training, started within 3 weeks after stroke onset and continued for 2 weeks, reduces upper limb impairment at 90 days after stroke as compared to sham stimulation.

METHODS AND DESIGN: We will perform a multicentre, double-blind, randomised, sham-controlled, clinical trial. Patients with ischaemic stroke or intracerebral haemorrhage and unilateral upper limb paresis will be assigned to receive 10 daily sessions of active or sham cTBS, delivered over the contralesional primary motor cortex, combined with regular care upper limb therapy and started within 3 weeks after stroke onset.

OUTCOMES: The primary outcome is the score of the Fugl-Meyer Upper Extremity (FM-UE) assessment at 90 days after stroke. Secondary outcomes are the FM-UE score at 12 months after stroke and scores on the Action Research Arm Test, Nine Hole Peg Test, modified Rankin Scale, Barthel Index, hand, participation and overall recovery sections of the Stroke Impact Scale and the EuroQol-5D-5L at 90 days and 12 months post-stroke. Additionally, cost-effectiveness, length of stay at the rehabilitation centre, and ipsilesional and contralesional excitability are assessed.

SAMPLE SIZE: We will randomise 454 participants 1:1 to active or sham cTBS. The sample size is based on a minimal detectable effect of 6.6 points on the FM-UE scale.

DISCUSSION: If cTBS treatment leads to a cost-effective and clinically meaningful additional recovery of at least 6.6 points on the FM-UE scale at 90 days after stroke, then cTBS treatment can be recommended as standard of care.