Clinical trial NCT01032239: SISTERS: Spasticity In Stroke Study - Randomized Study
Official title: A Randomized, Controlled, Open-label, Parallel-group, Multi-center Study to Compare the Effect of Intrathecal Baclofen Therapy Versus Best Medical Treatment on Severe Spasticity in Post-stroke Patients After 6 Months Active Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Severe Spasticity
Keywords: Severe spasticity in post-stroke patients
Lead sponsor: MedtronicNeuro
Sponsor class: INDUSTRY
First posted: 2009-12-15
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: Change in Average Ashworth Scale (AS) in Affected Lower Extremities From Baseline to Month 6
timeFrame: Baseline and month 6
Secondary outcomes:
measure: Change in Average Ashworth Scale (AS) in Affected Upper Extremities From Baseline to Month 6
timeFrame: Baseline and month 6
measure: Change in Functional Independence Measure (FIM) Score From Baseline to Month 6
timeFrame: Baseline and month 6
measure: Change in Average 10 Meter Time Walking Test (10MTWT) From Baseline to Month 6
timeFrame: Baseline and month 6
measure: Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance
timeFrame: baseline, month 3, month 6
measure: Change in Numeric Pain Rating Scale (NPRS) From Baseline to Month 6
timeFrame: Baseline and month 6
measure: Number of Participants Who Achieved Their Primary Therapeutic Goal Assessed With the Goal Attainment Scale (GAS)
timeFrame: month 6
measure: Change in Euro QoL Group-5 Dimensional, 3 Level Version (EQ-5D-3L) From Baseline to Month 6
timeFrame: Baseline and month 6
measure: Change in SF-12 (12-item Short Form) From Baseline to Month 6
timeFrame: Baseline and month 6
measure: Change in Stroke Specific Quality of Life (SS-QoL ) From Baseline to Month 6
timeFrame: Baseline and month 6
measure: Therapy Satisfaction
timeFrame: month 6
measure: Healthcare Resource Utilization
timeFrame: baseline, ITB test (only ITB arm), second assessment (only BMT arm), week 6 (only ITB arm), month 3, month 6
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Washington
country: United States
facility: MedStar National Rehabilitation Network
state: District of Columbia
city: Doral
country: United States
facility: Design Neuroscience Center
state: Florida
city: Orlando
country: United States
facility: Rehabilitation Medical Group - Florida Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Neurological Clinic Department of Neurosurgery
state: Florida
city: Boise
country: United States
facility: Saint Alphonsus Regional Med Center
state: Idaho
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Elkins Park
country: United States
facility: Einstein Hospital/Moss Rehabilitation
state: Pennsylvania
city: Houston
country: United States
facility: TIRR Memorial Herman Hospital
state: Texas
city: Vienna
country: Austria
facility: Sozialmedizinisches Zentrum Baumgartner Höhe Otto-Wagner-Spital
city: Zirl
country: Austria
facility: Landeskrankenhaus Hochzirl
city: Bruxelles
country: Belgium
facility: Clin. Univ. UCL Saint Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven, campus Pellenberg
city: Beelitz-Heilstätten
country: Germany
facility: Kliniken Beelitz GmbH Neurologische Rehabilitationsklinik
city: Bonn
country: Germany
facility: Ambulantes Neurologisches Rehabilitationszentrum
city: Burgau
country: Germany
facility: Therapiezentrum Burgau
city: Numbrecht
country: Germany
facility: Rhein-Sieg-Klinik Dr. Becker Klinikgesellschaft
city: Costa Masnaga
country: Italy
facility: Centro di Riabilitazione "Villa Beretta"
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri Clinica del lavoro e della riabilitazione IRCSS
city: Maastricht
country: Netherlands
facility: Afdeling Revalidatie Academisch Ziekenhuis Maastricht
city: Ljubljana
country: Slovenia
facility: Univerzitetni rehabilitacijski inštitut Republike Slovenije Soča
city: Barcelona
country: Spain
facility: Fundació Privada Institut de Neurorehabilitació Guttmann, Badalona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: London
country: United Kingdom
facility: St George's Hospital
Study officials:
affiliation: Landeskrankenhaus Hochzirl, Zirl (Austria)
name: Leopold SALTUARI, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Creamer M, Cloud G, Kossmehl P, Yochelson M, Francisco GE, Ward AB, Wissel J, Zampolini M, Abouihia A, Calabrese A, Saltuari L. Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity. Stroke. 2018 Sep;49(9):2129-2137. doi: 10.1161/STROKEAHA.118.022255.
citation: Creamer M, Cloud G, Kossmehl P, Yochelson M, Francisco GE, Ward AB, Wissel J, Zampolini M, Abouihia A, Berthuy N, Calabrese A, Loven M, Saltuari L. Intrathecal baclofen therapy versus conventional medical management for severe poststroke spasticity: results from a multicentre, randomised, controlled, open-label trial (SISTERS). J Neurol Neurosurg Psychiatry. 2018 Jun;89(6):642-650. doi: 10.1136/jnnp-2017-317021. Epub 2018 Jan 11.