Effect of adding upper limb rehabilitation to botulinum toxin-A on upper limb activity after stroke: Protocol for the InTENSE trial

Rationale: Although clinical practice guidelines recommend that management of moderate to severe spasticity include the use of botulinum toxin-A in conjunction with therapy, there is currently no evidence to support the addition of therapy. Aims: To determine the effect and cost-benefit of adding evidence-based movement training to botulinum toxin-A. Sample size estimate: A total of 136 participants will be recruited in order to be able to detect a between-group difference of seven points on the Goal Attainment Scale T-score with 80% power at a two-tailed significance level of 0.05. Methods and design: The InTENSE trial is a national, multicenter, Phase III randomized trial with concealed allocation, blinded assessment and intention-to-treat analysis. Stroke survivors who are scheduled to receive botulinum toxin-A in any muscle(s) that cross the wrist because of moderate to severe spasticity after a stroke greater than three months ago, who have completed formal rehabilitation and have no significant cognitive impairment will be randomly allocated to receive botulinum toxin-A plus evidence-based movement training or botulinum toxin-A alone. Study outcomes: The primary outcomes are goal attainment (Goal Attainment Scaling) and upper limb activity (Box and Block Test) at three months (end of intervention) and at 12 months (beyond the intervention). Secondary outcomes are spasticity, range of motion, strength, pain, burden of care and health-related quality of life. Direct costs, personal costs and health system costs will be collected at 12 months. Discussion: The results of the InTENSE trial are anticipated to directly influence intervention for moderate to severe spasticity after stroke. Trial Registration: ANZCTR12615000616572.