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

Abstract

Background: Intrathecal 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).

Results: Of 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.

Conclusions: These data support the use of ITB therapy as an alternative to CMM for treatment of generalised PSS in adults.

Trial registration number: NCT01032239; Results.

Figure 1

CONSORT (Consolidated Standards of Reporting Trials) flow diagram. CMM, conventional medical management; ITB, intrathecal baclofen; ITT, intention-to-treat.

Figure 2

Average AS score for the lower and upper limbs by study visit (ITT population). Mean (SEM) values for average AS score in the LE (panel A) and UE (panel B) of the affected side across patients by treatment arm (ITB vs CMM) and study visit. LOCF imputation was performed for the month 6 assessment using month 3 data; the number of patients analysed per visit is indicated. The second assessment (CMM arm) was done on day 21. AS, Ashworth Scale; CMM, conventional medical management (arm); ITB, intrathecal baclofen (arm); ITT, intention-to-treat; LE, lower extremities; LOCF, last observation carried forward; UE, upper extremities.

Figure 3

FIM total score by study visit (ITT population). LOCF imputation was performed for the month 6 assessment using month 3 data; the number of patients analysed per visit is indicated. CMM, conventional medical management (arm); FIM, Functional Independence Measure; ITB, intrathecal baclofen (arm); ITT, intention-to-treat; LOCF, last observation carried forward.

Figure 4

Frequency of treatment-related AEs (drug, device, procedure) over time during the study (modified ITT population). Second assessment: day 21±2 (CMM arm); week 6: day 44–67 (ITB arm) and corresponds to day 67 for CMM. AE, adverse event; CMM, conventional medical management; ITB, intrathecal baclofen; ITB-I, ITB-implanted; ITT, intention-to-treat.