Trial Outcomes & Findings for SISTERS: Spasticity In Stroke Study - Randomized Study (NCT NCT01032239)

Last Updated: 2018-02-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

61 participants

Primary outcome timeframe

Baseline and month 6

Results posted on

2018-02-15

Participant Flow

A total of 61 patients were enrolled. One patient did not meet the inclusion criteria (screening failure). 60 patients were then randomized into the study.

Participant milestones

Participant milestones
Measure	ITB Therapy Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) Use one or a combination oral antispastic medication
Overall Study STARTED	31	29
Overall Study Implant	25	0
Overall Study COMPLETED	24	24
Overall Study NOT COMPLETED	7	5

Reasons for withdrawal

Reasons for withdrawal
Measure	ITB Therapy Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) Use one or a combination oral antispastic medication
Overall Study Lost to Follow-up	3	2
Overall Study Withdrawal by Subject	2	3
Overall Study Death	1	0
Overall Study Protocol Violation	1	0

Baseline Characteristics

SISTERS: Spasticity In Stroke Study - Randomized Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ITB Therapy n=31 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=29 Participants Use one or a combination oral antispastic medication.	Total n=60 Participants Total of all reporting groups
Age, Continuous	56.09 years STANDARD_DEVIATION 11.12 • n=5 Participants	55.67 years STANDARD_DEVIATION 8.60 • n=7 Participants	55.89 years STANDARD_DEVIATION 9.90 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	18 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized White	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized Other	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Time since stroke	4.95 years STANDARD_DEVIATION 3.56 • n=5 Participants	4.55 years STANDARD_DEVIATION 3.73 • n=7 Participants	4.76 years STANDARD_DEVIATION 3.62 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method.

Outcome measures

Outcome measures
Measure	ITB Therapy n=25 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=26 Participants Use one or a combination oral antispastic medication.
Change in Average Ashworth Scale (AS) in Affected Lower Extremities From Baseline to Month 6	-0.99 units on a scale Standard Deviation 0.75	-0.43 units on a scale Standard Deviation 0.72

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method.

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=25 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=26 Participants Use one or a combination oral antispastic medication.
Change in Average Ashworth Scale (AS) in Affected Upper Extremities From Baseline to Month 6	-0.66 units on a scale Standard Deviation 0.59	-0.17 units on a scale Standard Deviation 0.70

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method.

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=25 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=26 Participants Use one or a combination oral antispastic medication.
Change in Functional Independence Measure (FIM) Score From Baseline to Month 6	2.68 units on a scale Standard Deviation 10.31	-2.58 units on a scale Standard Deviation 11.00

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method.Only High level functional patients (HLP) were analyzed. HLP were defined as patients able to transfer from the wheelchair to bed without human assistance.

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

Outcome measures

Outcome measures
Measure	ITB Therapy n=19 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=21 Participants Use one or a combination oral antispastic medication.
Change in Average 10 Meter Time Walking Test (10MTWT) From Baseline to Month 6	4.86 seconds Standard Deviation 59.82	-2.48 seconds Standard Deviation 65.60

SECONDARY outcome

Timeframe: baseline, month 3, month 6

Population: Intent to treat analysis

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=31 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=29 Participants Use one or a combination oral antispastic medication.
Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance Baseline · HLP	22 Participants	24 Participants
Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance Baseline · LLP	9 Participants	5 Participants
Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance Month 3 · HLP	19 Participants	21 Participants
Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance Month 3 · LLP	6 Participants	5 Participants
Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance Month 6 · HLP	19 Participants	19 Participants
Number of Participants Who Were Able to Transfer From the Wheelchair to Bed Without Human Assistance Month 6 · LLP	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method.

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=23 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=25 Participants Use one or a combination oral antispastic medication.
Change in Numeric Pain Rating Scale (NPRS) From Baseline to Month 6 Actual pain	-1.17 units on a scale Standard Deviation 3.17	0.00 units on a scale Standard Deviation 3.29
Change in Numeric Pain Rating Scale (NPRS) From Baseline to Month 6 Least Pain	-1.61 units on a scale Standard Deviation 2.29	0.24 units on a scale Standard Deviation 3.07
Change in Numeric Pain Rating Scale (NPRS) From Baseline to Month 6 Worst Pain	-1.35 units on a scale Standard Deviation 2.42	-0.04 units on a scale Standard Deviation 3.69

SECONDARY outcome

Timeframe: month 6

Population: Intent to treat analysis

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=24 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=24 Participants Use one or a combination oral antispastic medication.
Number of Participants Who Achieved Their Primary Therapeutic Goal Assessed With the Goal Attainment Scale (GAS) goal achieved	10 Participants	8 Participants
Number of Participants Who Achieved Their Primary Therapeutic Goal Assessed With the Goal Attainment Scale (GAS) goal not achieved	14 Participants	16 Participants

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method.

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=25 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=25 Participants Use one or a combination oral antispastic medication.
Change in Euro QoL Group-5 Dimensional, 3 Level Version (EQ-5D-3L) From Baseline to Month 6 Utility Score	0.09 units on a scale Standard Deviation 0.26	0.01 units on a scale Standard Deviation 0.16
Change in Euro QoL Group-5 Dimensional, 3 Level Version (EQ-5D-3L) From Baseline to Month 6 VAS	9.68 units on a scale Standard Deviation 20.42	4.40 units on a scale Standard Deviation 21.75

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method. SF-12 assessment has been introduced later in a second version of the protocol, hence the lower number of patients.

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=9 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=9 Participants Use one or a combination oral antispastic medication.
Change in SF-12 (12-item Short Form) From Baseline to Month 6 PCS	3.13 units on a scale Standard Deviation 3.47	-1.13 units on a scale Standard Deviation 6.63
Change in SF-12 (12-item Short Form) From Baseline to Month 6 MCS	1.05 units on a scale Standard Deviation 10.92	-0.82 units on a scale Standard Deviation 7.81

SECONDARY outcome

Timeframe: Baseline and month 6

Population: Intent to treat analysis. Last Observation Carried Forward (LOCF) imputation method.

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=24 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=25 Participants Use one or a combination oral antispastic medication.
Change in Stroke Specific Quality of Life (SS-QoL ) From Baseline to Month 6	0.26 units on a scale Standard Deviation 0.58	0.05 units on a scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: month 6

Population: Intent to treat analysis.

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.

Outcome measures

Outcome measures
Measure	ITB Therapy n=22 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=23 Participants Use one or a combination oral antispastic medication.
Therapy Satisfaction Patient Satisfaction with Spasticity Reduction · disagree	2 Participants	7 Participants
Therapy Satisfaction Patient Satisfaction with Spasticity Reduction · neutral	4 Participants	5 Participants
Therapy Satisfaction Patient Satisfaction with Spasticity Reduction · agree	16 Participants	11 Participants
Therapy Satisfaction Patient Therapy Reccomandation · disagree	3 Participants	5 Participants
Therapy Satisfaction Patient Therapy Reccomandation · neutral	3 Participants	4 Participants
Therapy Satisfaction Patient Therapy Reccomandation · agree	16 Participants	14 Participants

SECONDARY outcome

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

Population: Intent to treat analysis.

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

Outcome measures

Outcome measures
Measure	ITB Therapy n=31 Participants Intrathecal Baclofen therapy (Intrathecal baclofen + implantable pump)	Best Medical Treatment (BMT) n=29 Participants Use one or a combination oral antispastic medication.
Healthcare Resource Utilization month 6: other	8 Participants	11 Participants
Healthcare Resource Utilization Baseline : general practitioner	14 Participants	8 Participants
Healthcare Resource Utilization Baseline : neurologist	4 Participants	8 Participants
Healthcare Resource Utilization Baseline : nurse (hospital setting)	1 Participants	0 Participants
Healthcare Resource Utilization Baseline : nurse (home care)	0 Participants	1 Participants
Healthcare Resource Utilization Baseline : orthopedic surgeon	3 Participants	0 Participants
Healthcare Resource Utilization Baseline : other	10 Participants	13 Participants
Healthcare Resource Utilization ITB test:general practitioner	1 Participants	NA Participants ITB test visit is not applicable for the BMT arm
Healthcare Resource Utilization ITB test: neurologist	1 Participants	NA Participants ITB test visit is not applicable for the BMT arm
Healthcare Resource Utilization ITB test :other	3 Participants	NA Participants ITB test visit is not applicable for the BMT arm
Healthcare Resource Utilization Second Assessment: general practitioner	NA Participants Second assessemnt visit is not applicable for the ITB arm	5 Participants
Healthcare Resource Utilization Second Assessment: neurologist	NA Participants Second assessemnt visit is not applicable for the ITB arm	1 Participants
Healthcare Resource Utilization Second Assessment: nurse (home care)	NA Participants Second assessemnt visit is not applicable for the ITB arm	1 Participants
Healthcare Resource Utilization Second Assessment: other	NA Participants Second assessemnt visit is not applicable for the ITB arm	4 Participants
Healthcare Resource Utilization week 6: general practitioner	4 Participants	NA Participants week 6 visit is not applicable for the BMT arm
Healthcare Resource Utilization week 6: nurse (hospital setting)	2 Participants	NA Participants week 6 visit is not applicable for the BMT arm
Healthcare Resource Utilization week 6: other	2 Participants	NA Participants week 6 visit is not applicable for the BMT arm
Healthcare Resource Utilization month 3: general practitioner	7 Participants	8 Participants
Healthcare Resource Utilization month 3: neurologist	1 Participants	3 Participants
Healthcare Resource Utilization month 3: other	6 Participants	9 Participants
Healthcare Resource Utilization month 6: general practitioner	8 Participants	7 Participants
Healthcare Resource Utilization month 6: neurologist	3 Participants	2 Participants

Adverse Events

ITB-I

Serious events: 12 serious events

Other events: 23 other events

Deaths: 1 deaths

BMT+ITB-NI

Serious events: 10 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Alessandra Calabrese, PhD

Medtronic Clinical Neuromodulation

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Serious adverse events
Measure	ITB-I n=25 participants at risk Patients implanted with intrathecal baclofen pump	BMT+ITB-NI n=35 participants at risk Patients randomized to BMT plus patients randomized to ITB but not implanted (treated with one or a combination oral antispastic medication)
Infections and infestations Urinary tract infection	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	5.7% 2/35 • Number of events 5 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Implant site infection	8.0% 2/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Cystitis	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Pharyngitis	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Pneumonia bacterial	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Epilepsy	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Cerebrovascular accident	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Dizziness	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Hemiparesis	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Intracranial hypotension	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Muscle spasticity	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Normal pressure hydrocephalus	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Nervous system disorders Transient ischaemic attack	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Renal and urinary disorders Nephrolithiasis	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 3 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Renal and urinary disorders Urinary retention	8.0% 2/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Renal and urinary disorders Hydronephrosis	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Device dislocation	8.0% 2/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Device occlusion	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Implant site effusion	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Oedema peripheral	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Pain	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Injury, poisoning and procedural complications Alcohol poisoning	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Injury, poisoning and procedural complications Fall	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Injury, poisoning and procedural complications Suture related complication	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Musculoskeletal and connective tissue disorders Arthralgia	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Musculoskeletal and connective tissue disorders Mobility decreased	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Musculoskeletal and connective tissue disorders Muscular weakness	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Cardiac disorders Diastolic dysfunction	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Cardiac disorders Mitral valve stenosis	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Cardiac disorders Supraventricular tachycardia	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Psychiatric disorders Mental disorder	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Psychiatric disorders Depression	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Constipation	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Faecaloma	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Gastritis	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Eye disorders Cataract	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Eye disorders Diabetic retinopathy	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.

Other adverse events
Measure	ITB-I n=25 participants at risk Patients implanted with intrathecal baclofen pump	BMT+ITB-NI n=35 participants at risk Patients randomized to BMT plus patients randomized to ITB but not implanted (treated with one or a combination oral antispastic medication)
Ear and labyrinth disorders Cerumen impaction	8.0% 2/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Ear and labyrinth disorders Tinnitus	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Ear and labyrinth disorders Vertigo	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Eye disorders Cataract	4.0% 1/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Eye disorders Conjunctivitis	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Eye disorders Eyelid oedema	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Eye disorders Vision blurred	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Constipation	12.0% 3/25 • Number of events 3 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Diarrhoea	12.0% 3/25 • Number of events 3 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Dyspepsia	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Dysphagia	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Faecaloma	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Flatulence	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Gastritis	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Hypoaesthesia oral	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Nausea	4.0% 1/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Toothache	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Gastrointestinal disorders Vomiting	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Implant site pain	8.0% 2/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Oedema peripheral	8.0% 2/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	5.7% 2/35 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Pain	16.0% 4/25 • Number of events 4 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	8.6% 3/35 • Number of events 3 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Adverse drug reaction	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Asthenia	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Chronic fatigue syndrome	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Fatigue	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Gait disturbance	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Implant site reaction	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
General disorders Pyrexia	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Immune system disorders Drug hypersensitivity	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Immune system disorders Hypersensitivity	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Upper respiratory tract infection	8.0% 2/25 • Number of events 2 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Urinary tract infection	12.0% 3/25 • Number of events 4 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Bronchitis	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Bronchopneumonia	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Influenza	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Lower respiratory tract infection	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Nail infection	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Nasopharyngitis	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	0.00% 0/35 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Respiratory tract infection	0.00% 0/25 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.
Infections and infestations Ear infection	4.0% 1/25 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.	2.9% 1/35 • Number of events 1 • From ITB test (for ITB arm) and randomization (for BMT arm) untill month 6 follow-up visit Safety analyses were performed on a modified ITT (intent to treat) patient set: all patients were analyzed as treated; ITB-I included only implated patients. BMT+ITB-NI included also patients randomized to ITB, but not implanted.