Intrathecal baclofen therapy versus conventional medical management for severe poststroke spasticity: results from a multicentre, randomised, controlled, open-label trial (SISTERS)

Abstract

BackgroundIntrathecal baclofen (ITB) is a treatment option for patients with severe poststroke spasticity (PSS) who have not reached their therapy goal with other interventions.Methods’Spasticity In Stroke–Randomised Study' (SISTERS) was a randomised, controlled, open-label, multicentre phase IV study to evaluate the efficacy and safety of ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of PSS. Patients with chronic stroke with spasticity in ≥2 extremities and an Ashworth Scale (AS) score ≥3 in at least two affected muscle groups in the lower extremities (LE) were randomised (1:1) to ITB or CMM. Both treatment arms received physiotherapy throughout. The primary outcome was the change in the average AS score in the LE of the affected body side from baseline to month 6. Analyses were performed for all patients as randomised (primary analysis) and all randomised patients as treated (safety analysis).ResultsOf 60 patients randomised to ITB (n=31) or CMM (n=29), 48 patients (24 per arm) completed the study. The primary analysis showed a significant effect of ITB therapy over CMM (mean AS score reduction, −0.99 (ITB) vs −0.43 (CMM); Hodges-Lehmann estimate, −0.667(95.1%CI −1.0000 to −0.1667); P=0.0140). More patients reported adverse events while receiving ITB (24/25 patients, 96%; 149 events) compared with CMM (22/35, 63%; 77 events), although events were generally consistent with the known safety profile of ITB therapy.ConclusionsThese data support the use of ITB therapy as an alternative to CMM for treatment of generalised PSS in adults.Trial registration numberNCT01032239; Results.

Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity

“…In line with current standards of care, both treatment arms received physiotherapy throughout the study. Results for the primary outcome, published previously, 19 showed a significant effect of treatment with ITB therapy over CMM for reduction of spasticity in the lower limb measured with the Ashworth Scale over 6-month follow-up. Furthermore, although the study was not powered for analysis of secondary outcomes, we observed a statistically significant treatment effect for ITB over CMM for spasticity reduction in the upper limb, indicating a substantial and broad effect of ITB therapy in PSS control.…”

“…Twenty-five patients in the ITB arm were implanted with the device; of the 6 who were not implanted, 1 withdrew consent before the ITB test, 2 were lost to follow-up after the ITB test, and 3 were switched to CMM as previously described. 19 Twelve patients (7/31 [23%] and 5/29 [17%] in the ITB and CMM arms, respectively) discontinued prematurely and 48 patients completed follow-up at month 6 (24/31 [77%] in the ITB arm, including 22 implanted patients, versus 24/29 [83%] in the CMM arm). One ITB-implanted patient died after week 6 because of an unrelated cause (neither study drug nor study device).…”

“…Full details on the design of SISTERS, including the sample size calculation and randomization methods, have been reported previously. 19 The study evaluated the efficacy and safety of ITB therapy compared with CMM with oral antispastic medications on severe spasticity in poststroke patients after 6 months active treatment. For the purposes of this study, a stroke was defined as any acute vascular accident (ischemic or hemorrhagic).…”

“…Results for the study’s primary outcome (spastic hypertonia and muscle tone in the affected lower limb, as assessed by the change in average Ashworth Scale score from baseline to month 6) and safety have been reported previously. 19 …”

Intrathecal Baclofen for Severe Spasticity: Longitudinal Data From the Product Surveillance Registry

“…ITB therapy was originally evaluated for the treatment of severe spasticity of spinal origin (9,10), with indications expanded to include severe spasticity of cerebral origin, including cerebral palsy (11), brain injury (12), and stroke (13)(14)(15). Previous studies have demonstrated efficacy in spasticity of multiple origins, with long-term benefits (11,(16)(17)(18).…”