SISTERS: Spasticity In Stroke Study - Randomized Study

To demonstrate that Intrathecal Baclofen (ITB) Therapy, compared to Best Medical Treatment (BMT), has superior efficacy in the treatment of severe spasticity in adult post-stroke patients with generalized spastic hypertonia who have not reached their therapy goal with other treatment interventions assessed by a decrease in the average Ashworth Scale (AS) score in the lower extremities.

This is a randomized, controlled open-label parallel group study to demonstrate the efficacy benefit of ITB Therapy over BMT in post-stroke patients with severe spasticity who have not reached their therapy goal with other treatment interventions.

In order to evaluate the efficacy benefit of ITB Therapy over BMT in post-stroke patients, a two-arm parallel group design will be applied. Patients will be equally randomized to one of two treatment arms:

1. ITB Therapy arm; or
2. BMT arm

The study consists of a run-in phase of 21 days for the BMT treatment arm and 2-25 days for the ITB Therapy treatment arm, followed by a 6 month active trial.

The BMT treatment arm will receive a combination of oral antispastic medication and physiotherapy. Patients must be prescribed at least one or a combination of the following oral antispastic medications: oral baclofen, tizanidine, diazepam (or other benzodiazepines) or dantrolene. Following the run-in phase, patients will enter the 6 month active trial.

The ITB Therapy treatment arm will receive a combination of ITB Therapy and physiotherapy. During the run-in phase, a test with intrathecal baclofen will be performed to evaluate the response of the patient. Patients fulfilling the test success criterium will be implanted with a Medtronic SynchroMed®II infusion system. Following implant, patients will enter into the 6 month active trial, which includes a 6 week titration phase, during which time oral antispastic medications must be gradually reduced with complete discontinuation by the end of the titration period.

During the 6 month active trial, patients will be assessed at 3 and 6 months. All primary and secondary endpoint assessments will be performed by a blinded assessor.

The total study duration is expected to be 60 months, including a 39 month enrollment period. The total duration per patient is approximately 7 months (approximately 1 month run-in period followed by 6 months active treatment).

Eligibility Criteria:
Inclusion criteria:

To be eligible for inclusion into this study, patients must fulfill all of the following criteria prior to study enrollment:

1. patient (or legal guardian) has been informed of the study procedures and has given written informed consent
2. patient experienced last stroke \> 6 months prior to enrollment
3. patient presents spasticity in at least 2 extremities
4. patient presents an Ashworth score ≥ 3 in a minimum of two of the affected muscle groups in the lower extremities
5. patient is eligible to receive ITB Therapy following the Adult Spasticity Algorithm. A patient does not reach his/her therapy goal with other treatment interventions
6. stable blood pressure: no change in hypertensive medication in last month (NOTE: ventriculoperitoneal shunts and valves can be present)
7. if female, she must either be post-menopausal or surgically sterilized; or use a hormonal contraceptive, intrauterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study
8. patient/family is willing to comply with study protocol including attending the study visits

Exclusion criteria:

To be eligible for inclusion in this study the patients must not meet any of the following criteria:

1. patient/family is considered by the physician to be unable or unwilling to participate in long-term ITB Therapy management
2. patient has known hypersensitivity to baclofen
3. active systemic infection (NOTE: pressure sores are not a contraindication unless they are present near the implant sites)
4. presence of a cardiac pacemaker, ICD, implantable neurostimulator or drug delivery device
5. uncontrolled refractory epilepsy
6. use of oral vitamin K antagonists, e.g. warfarin/coumadin; unless the patient can switch to another accepted anticoagulant (e.g. heparin, aggrenox, fragmin, plavix, ticlid) for the period of ITB test and implant
7. patient is pregnant or breastfeeding
8. patient received a Botulinum toxin injection less than 4 months ago