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SISTERS: Spasticity In Stroke Study - Randomized Study (SISTERS)

Primary Purpose

Severe Spasticity

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

intrathecal baclofen

About this trial

This is an interventional treatment trial for Severe Spasticity focused on measuring Severe spasticity in post-stroke patients

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

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

patient (or legal guardian) has been informed of the study procedures and has given written informed consent
patient experienced last stroke > 6 months prior to enrollment
patient presents spasticity in at least 2 extremities
patient presents an Ashworth score ≥ 3 in a minimum of two of the affected muscle groups in the lower extremities
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
stable blood pressure: no change in hypertensive medication in last month (NOTE: ventriculoperitoneal shunts and valves can be present)
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
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:

patient/family is considered by the physician to be unable or unwilling to participate in long-term ITB Therapy management
patient has known hypersensitivity to baclofen
active systemic infection (NOTE: pressure sores are not a contraindication unless they are present near the implant sites)
presence of a cardiac pacemaker, ICD, implantable neurostimulator or drug delivery device
uncontrolled refractory epilepsy
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
patient is pregnant or breastfeeding
patient received a Botulinum toxin injection less than 4 months ago

Sites / Locations

University of California Irvine
MedStar National Rehabilitation Network
Design Neuroscience Center
Rehabilitation Medical Group - Florida Hospital
Tallahassee Neurological Clinic Department of Neurosurgery
Saint Alphonsus Regional Med Center
Research Medical Center
Einstein Hospital/Moss Rehabilitation
TIRR Memorial Herman Hospital
Sozialmedizinisches Zentrum Baumgartner Höhe Otto-Wagner-Spital
Landeskrankenhaus Hochzirl
Clin. Univ. UCL Saint Luc
Universitair Ziekenhuis Gent
Universitaire Ziekenhuizen Leuven, campus Pellenberg
Kliniken Beelitz GmbH Neurologische Rehabilitationsklinik
Ambulantes Neurologisches Rehabilitationszentrum
Therapiezentrum Burgau
Rhein-Sieg-Klinik Dr. Becker Klinikgesellschaft
Centro di Riabilitazione "Villa Beretta"
Fondazione Salvatore Maugeri Clinica del lavoro e della riabilitazione IRCSS
Afdeling Revalidatie Academisch Ziekenhuis Maastricht
Univerzitetni rehabilitacijski inštitut Republike Slovenije Soča
Fundació Privada Institut de Neurorehabilitació Guttmann, Badalona
Hospital Universitario La Paz
St George's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

ITB therapy

Best Medical Treatment (BMT)

Arm Description

Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)

Use one or a combination oral antispastic medication.

Outcomes

Primary Outcome Measures

Change in Average Ashworth Scale (AS) in Affected Lower Extremities From Baseline to Month 6

AS is a manual test, measuring the resistance to passive movement about a joint with varying degrees of velocity. Scores range from 1-5, with 5 choices. A score of 1 indicates no resistance, and 5 indicates rigidity. The following muscle groups in the lower extremities were assessed: hip flexors, hip adductors, knee extensors, knee flexors, plantar flexors and ankle-dorsal flexors. Average AS was calculated as the average of AS scores of the 6 muscles of the affected lower extremity. Change in average AS in affected lower extremities from baseline to month 6 between ITB and BMT arm was assessed. Change= AS at month 6 - AS at baseline.

Secondary Outcome Measures

Change in Average Ashworth Scale (AS) in Affected Upper Extremities From Baseline to Month 6

AS is a manual test, measuring the resistance to passive movement about a joint with varying degrees of velocity. Scores range from 1-5, with 5 choices. A score of 1 indicates no resistance, and 5 indicates rigidity. The following muscle groups in the upper extremities were assessed: wrist flexors, elbow flexors, elbow extensors, shoulder abductors and shoulder adductors. Average AS was calculated as the average of AS scores of the 5 muscles of the affected lower extremities. Change in average AS in affected upper extremities from baseline to month 6 between ITB and BMT arm was assessed. Change= AS at month 6 - AS at baseline.

Change in Functional Independence Measure (FIM) Score From Baseline to Month 6

FIM contains 18 items composed of 13 motor tasks and 5 cognitive tasks. Tasks are rated on a 7-point ordinal scale that ranges from total assistance (or complete dependence) to complete independence. Ratings should reflect actual observed performance, not capability. Total score ranges from 18 (lowest) to 126 (highest) level of independence. Change in FIM total score from baseline to month 6 between ITB and BMT arm was assessed. Change=FIM score at month 6 - FIM score at baseline.

Change in Average 10 Meter Time Walking Test (10MTWT) From Baseline to Month 6

Change in average 10MTWT from baseline to month 6 beetween ITB and BMT arm. Change=10MTWT at month 6 - 10MTWT at baseline

Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance

Patient was asked to transfer from the wheelchair to bed without human assistance. High level functional patient (HLP) could transfer. Low level functional patient (LLP) was not able to transfer. Comparison of the number and percentage of HLP and LLP between ITB and BMT arms was evaluated.

Change in Numeric Pain Rating Scale (NPRS) From Baseline to Month 6

NPRS is designed to assess the level of pain a patient is feeling at a point in time. The following questions has been presented to patients: What is your actual spasticity-related or spasm-related pain? What was your least spasticity-related or spasm-related pain during the last week? What was your worst spasticity-related or spasm-related pain during the last week? The patient indicated how much pain he is feeling on a scale from 0 to 10. A score of 0 (zero) is "no pain" while a score of 10 (ten) is "worst possible pain". Change in NPRS related to actual, least or worst pain from baseline to month 6 between ITB and BMT arm was assessed. Change=NPRS at month 6 - NPRS at baseline.

Number of Participants Who Achieved Their Primary Therapeutic Goal Assessed With the Goal Attainment Scale (GAS)

GAS is designed to measure the achievement of treatment goals using the following 6 levels of achievement: worse than start (-3), much less than expected (-2), somewhat less than expected (-1), as expected (0), somewhat more than expected (+1), much more than expected (+2). The primary therapy goal and the criteria for the levels of achievement was defined by the medical team together with the patient and his/her family/legal representative/caregiver at the first day of the study. The number and percentage of patients who achieved the therapeutic goal at Month 6 was compared between the ITB and BMT arm.

Change in Euro QoL Group-5 Dimensional, 3 Level Version (EQ-5D-3L) From Baseline to Month 6

The EQ-5D-3L is a generic measure of health status consisting in the EQ-5D-3L descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system is characterized on five dimensions: mobility, self-care, ability to undertake usual activities, pain and anxiety/depression. Patients were asked to indicate their level of health on each dimension using one of three levels: "no health problems", "moderate health problems", and "severe health problems". Responses from the questionnaire were converted to a single health index utility score; this ranges from -0.595 to 1. EQ VAS records the patient's self-rated health on a vertical visual analogue scale from 0 to 100 where the endpoints are labelled 'Best imaginable health state' (100) and 'Worst imaginable health state' (0). Change in EQ-5D-3L utility score and VAS score from baseline to month 6 between ITB and BMT arm were assessed. Change=EQ-5D-3L utility or VAS score at month 6 - EQ-5D-3L utility or VAS score.

Change in SF-12 (12-item Short Form) From Baseline to Month 6

The SF-12 is generic assessment of health-related quality of life, which evaluates 8 health dimensions (physical functioning, role physical, bodily pain, vitality, social functioning, role emotional, mental health, and general health). Subscale scores for each dimension were aggregated into summary scores for physical (PCS) and mental health (MCS) components (ranging from 0 to 100, with higher scores indicating better health). Changes in the PCS and MCS from baseline to Month 6 were both compared between the BMT and ITB arms. Change=SF-12 score at month 6 - SF-12 score at baseline.

Change in Stroke Specific Quality of Life (SS-QoL ) From Baseline to Month 6

SS-QoL questionnaire is a self-assessed quality of life questionnaire specifically designed for post-stroke patients. It evaluates 49 items across 12-domains: personality, energy, language, mobility, vision, upper extremity function, thinking, mood, work/productivity, self-care, and family and social roles. Each item is rated on a 5-point Likert Scale, measuring either positive or negative response to a statement. Summary score is composed of an unweighted average of the 12 domain scores, with higher scores indicating better QoL. Total score ranges from 1 to 5. Change in SS-QoL summary score from baseline to month 6 between ITB and BMT arm was assessed. Change=SS-QoL score at month 6 - SS-QoL score at baseline.

Therapy Satisfaction

Patients were presented with two statements ("I am satisfied with the reduction in spasticity provided by my treatment", and "I would recommend this therapy to a friend"). They agreed, disagreed or were neutral with the statements.

Healthcare Resource Utilization

Number of patients with healthcare professional contacts outside of study visits in the ITB and BMT between baseline and months 6

Full Information

NCT ID

NCT01032239

First Posted

December 7, 2009

Last Updated

January 18, 2018

Sponsor

MedtronicNeuro

1. Study Identification

Unique Protocol Identification Number

NCT01032239

Brief Title

SISTERS: Spasticity In Stroke Study - Randomized Study

Acronym

SISTERS

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

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

September 2016 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedtronicNeuro

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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: ITB Therapy arm; or 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Spasticity

Keywords

Severe spasticity in post-stroke patients

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

61 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ITB therapy

Arm Type

Active Comparator

Arm Description

Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)

Arm Title

Best Medical Treatment (BMT)

Arm Type

No Intervention

Arm Description

Use one or a combination oral antispastic medication.

Intervention Type

Drug

Intervention Name(s)

intrathecal baclofen

Intervention Description

ITB test, implant, 6 months follow-up

Primary Outcome Measure Information:

Title

Change in Average Ashworth Scale (AS) in Affected Lower Extremities From Baseline to Month 6

Description

Time Frame

Baseline and month 6

Secondary Outcome Measure Information:

Title

Change in Average Ashworth Scale (AS) in Affected Upper Extremities From Baseline to Month 6

Description

AS is a manual test, measuring the resistance to passive movement about a joint with varying degrees of velocity. Scores range from 1-5, with 5 choices. A score of 1 indicates no resistance, and 5 indicates rigidity. The following muscle groups in the upper extremities were assessed: wrist flexors, elbow flexors, elbow extensors, shoulder abductors and shoulder adductors. Average AS was calculated as the average of AS scores of the 5 muscles of the affected lower extremities. Change in average AS in affected upper extremities from baseline to month 6 between ITB and BMT arm was assessed. Change= AS at month 6 - AS at baseline.

Time Frame

Baseline and month 6

Title

Change in Functional Independence Measure (FIM) Score From Baseline to Month 6

Description

Time Frame

Baseline and month 6

Title

Change in Average 10 Meter Time Walking Test (10MTWT) From Baseline to Month 6

Description

Change in average 10MTWT from baseline to month 6 beetween ITB and BMT arm. Change=10MTWT at month 6 - 10MTWT at baseline

Time Frame

Baseline and month 6

Title

Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance

Description

Time Frame

baseline, month 3, month 6

Title

Change in Numeric Pain Rating Scale (NPRS) From Baseline to Month 6

Description

Time Frame

Baseline and month 6

Title

Number of Participants Who Achieved Their Primary Therapeutic Goal Assessed With the Goal Attainment Scale (GAS)

Description

Time Frame

month 6

Title

Change in Euro QoL Group-5 Dimensional, 3 Level Version (EQ-5D-3L) From Baseline to Month 6

Description

Time Frame

Baseline and month 6

Title

Change in SF-12 (12-item Short Form) From Baseline to Month 6

Description

Time Frame

Baseline and month 6

Title

Change in Stroke Specific Quality of Life (SS-QoL ) From Baseline to Month 6

Description

Time Frame

Baseline and month 6

Title

Therapy Satisfaction

Description

Time Frame

month 6

Title

Healthcare Resource Utilization

Description

Number of patients with healthcare professional contacts outside of study visits in the ITB and BMT between baseline and months 6

Time Frame

baseline, ITB test (only ITB arm), second assessment (only BMT arm), week 6 (only ITB arm), month 3, month 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: To be eligible for inclusion into this study, patients must fulfill all of the following criteria prior to study enrollment: patient (or legal guardian) has been informed of the study procedures and has given written informed consent patient experienced last stroke > 6 months prior to enrollment patient presents spasticity in at least 2 extremities patient presents an Ashworth score ≥ 3 in a minimum of two of the affected muscle groups in the lower extremities 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 stable blood pressure: no change in hypertensive medication in last month (NOTE: ventriculoperitoneal shunts and valves can be present) 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 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: patient/family is considered by the physician to be unable or unwilling to participate in long-term ITB Therapy management patient has known hypersensitivity to baclofen active systemic infection (NOTE: pressure sores are not a contraindication unless they are present near the implant sites) presence of a cardiac pacemaker, ICD, implantable neurostimulator or drug delivery device uncontrolled refractory epilepsy 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 patient is pregnant or breastfeeding patient received a Botulinum toxin injection less than 4 months ago

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Leopold SALTUARI, Prof.

Organizational Affiliation

Landeskrankenhaus Hochzirl, Zirl (Austria)

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California Irvine

City

Irvine

State/Province

California

ZIP/Postal Code

92697

Country

United States

Facility Name

MedStar National Rehabilitation Network

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Design Neuroscience Center

City

Doral

State/Province

Florida

ZIP/Postal Code

33172

Country

United States

Facility Name

Rehabilitation Medical Group - Florida Hospital

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Tallahassee Neurological Clinic Department of Neurosurgery

City

Tallahassee

State/Province

Florida

ZIP/Postal Code

32308

Country

United States

Facility Name

Saint Alphonsus Regional Med Center

City

Boise

State/Province

Idaho

ZIP/Postal Code

83704

Country

United States

Facility Name

Research Medical Center

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64132

Country

United States

Facility Name

Einstein Hospital/Moss Rehabilitation

City

Elkins Park

State/Province

Pennsylvania

ZIP/Postal Code

19027-2220

Country

United States

Facility Name

TIRR Memorial Herman Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Sozialmedizinisches Zentrum Baumgartner Höhe Otto-Wagner-Spital

City

Vienna

ZIP/Postal Code

1140

Country

Austria

Facility Name

Landeskrankenhaus Hochzirl

City

Zirl

ZIP/Postal Code

6170

Country

Austria

Facility Name

Clin. Univ. UCL Saint Luc

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Universitair Ziekenhuis Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Universitaire Ziekenhuizen Leuven, campus Pellenberg

City

Leuven

ZIP/Postal Code

B-3000

Country

Belgium

Facility Name

Kliniken Beelitz GmbH Neurologische Rehabilitationsklinik

City

Beelitz-Heilstätten

ZIP/Postal Code

14547

Country

Germany

Facility Name

Ambulantes Neurologisches Rehabilitationszentrum

City

Bonn

ZIP/Postal Code

53117

Country

Germany

Facility Name

Therapiezentrum Burgau

City

Burgau

ZIP/Postal Code

89331

Country

Germany

Facility Name

Rhein-Sieg-Klinik Dr. Becker Klinikgesellschaft

City

Numbrecht

ZIP/Postal Code

51588

Country

Germany

Facility Name

Centro di Riabilitazione "Villa Beretta"

City

Costa Masnaga

ZIP/Postal Code

23845

Country

Italy

Facility Name

Fondazione Salvatore Maugeri Clinica del lavoro e della riabilitazione IRCSS

City

Pavia

ZIP/Postal Code

27100

Country

Italy

Facility Name

Afdeling Revalidatie Academisch Ziekenhuis Maastricht

City

Maastricht

ZIP/Postal Code

6229

Country

Netherlands

Facility Name

Univerzitetni rehabilitacijski inštitut Republike Slovenije Soča

City

Ljubljana

ZIP/Postal Code

1000

Country

Slovenia

Facility Name

Fundació Privada Institut de Neurorehabilitació Guttmann, Badalona

City

Barcelona

ZIP/Postal Code

08916

Country

Spain

Facility Name

Hospital Universitario La Paz

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

St George's Hospital

City

London

ZIP/Postal Code

SW17 0 QT

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

30354975

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.

Results Reference

derived

PubMed Identifier

29326296

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.

Results Reference

derived

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SISTERS: Spasticity In Stroke Study - Randomized Study

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