SISTERS: Spasticity In Stroke Study - Randomized Study

NCT ID: NCT01032239

Last Updated: 2018-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2016-09-30

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).

Conditions

Severe Spasticity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ITB therapy

Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)

Group Type: ACTIVE_COMPARATOR

intrathecal baclofen

Intervention Type: DRUG

ITB test, implant, 6 months follow-up

Best Medical Treatment (BMT)

Use one or a combination oral antispastic medication.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

intrathecal baclofen

ITB test, implant, 6 months follow-up

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedtronicNeuro

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leopold SALTUARI, Prof.

Role: PRINCIPAL_INVESTIGATOR

Landeskrankenhaus Hochzirl, Zirl (Austria)

Locations

University of California Irvine

Irvine, California, United States

MedStar National Rehabilitation Network

Washington D.C., District of Columbia, United States

Design Neuroscience Center

Doral, Florida, United States

Rehabilitation Medical Group - Florida Hospital

Orlando, Florida, United States

Tallahassee Neurological Clinic Department of Neurosurgery

Tallahassee, Florida, United States

Saint Alphonsus Regional Med Center

Boise, Idaho, United States

Research Medical Center

Kansas City, Missouri, United States

Einstein Hospital/Moss Rehabilitation

Elkins Park, Pennsylvania, United States

TIRR Memorial Herman Hospital

Houston, Texas, United States

Sozialmedizinisches Zentrum Baumgartner Höhe Otto-Wagner-Spital

Vienna, , Austria

Landeskrankenhaus Hochzirl

Zirl, , Austria

Clin. Univ. UCL Saint Luc

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Universitaire Ziekenhuizen Leuven, campus Pellenberg

Leuven, , Belgium

Kliniken Beelitz GmbH Neurologische Rehabilitationsklinik

Beelitz-Heilstätten, , Germany

Ambulantes Neurologisches Rehabilitationszentrum

Bonn, , Germany

Therapiezentrum Burgau

Burgau, , Germany

Rhein-Sieg-Klinik Dr. Becker Klinikgesellschaft

Nümbrecht, , Germany

Centro di Riabilitazione "Villa Beretta"

Costa Masnaga, , Italy

Fondazione Salvatore Maugeri Clinica del lavoro e della riabilitazione IRCSS

Pavia, , Italy

Afdeling Revalidatie Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Univerzitetni rehabilitacijski inštitut Republike Slovenije Soča

Ljubljana, , Slovenia

Fundació Privada Institut de Neurorehabilitació Guttmann, Badalona

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

St George's Hospital

London, , United Kingdom

Countries

United States; Austria; Belgium; Germany; Italy; Netherlands; Slovenia; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 30354975 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29326296 (View on PubMed)

Other Identifiers

1.02.7001

Identifier Type: -

Identifier Source: org_study_id