Interventional procedure overview of neurostimulation of lumbar muscles for refractory non-specific chronic low back pain

Randomised sham-controlled trial (ReActiv8-B Study NCT02577354)

International study -United States, Australia, and Europe

(26 centres)

2016 to 2018

n=204 patients with refractory mechanical chronic low back pain (CMLBP) and impaired multifidus control implanted with a neurostimulator.

Treatment group (therapeutic stimulation, n=102) versus control group (low-level sham stimulation, n=102)

Duration of back pain: mean 14±11 years

Percent of days with LBP in past year: 97±8%

Treatment group: mean age 46±10 years; 55% (56/102) female

Sham control group: mean age 48±9 years; 53% (54/102) female

Inclusion criteria: patients between 22 to 75 years, with continuing and refractory CMLBP (despite more than 90 days of medical management and no specified physical therapy); reported a 7-day recall of average LBP of ≥6.0 and ≤9.0 cm (on the 10-cm visual analogue scale, VAS); had an Oswestry Disability Index (ODI) of ≥21 and ≤60 points (on a scale from 0 to 100); and had a positive prone instability test suggesting impaired motor control of the multifidus muscle and lumbar segmental instability.

Exclusion criteria: prior lumbar spine surgery below T8, any previous rhizotomy or rhizolysis procedure on the dorsal root ganglion or medial branch at or below T8; anaesthetic block or epidural steroids at or below T8, spinal fusion at any level; CLBP amenable to surgery; leg pain worse than back pain, or radiculopathy below the knee; neurological deficit with back pain; sacroiliac joint pain; scoliosis or correction surgery, comorbid pain conditions; opioid use of more than 120 mg; any pain-related disability, compensation or litigation issues; psychological or psychiatric disorder.

Neurostimulator device (ReActiv8, Mainstay Medical Limited) was implanted to simulate the medial branch of the dorsal ramus nerve to elicit episodic contraction of the lumbar multifidus.

Devices were activated and therapeutic stimulation in treatment group was programmed at a frequency of 20 Hz, a pulse width of 214 microseconds and participant-specific pulse amplitudes and configurations to elicit contractions for 10 seconds twice per minute during the stimulation session. For the sham-control group stimulation parameters were programmed to low amplitude and frequency values (unipolar stimulation from the proximal electrode with 3 stimulation pulses of 0.1mA and 31microseconds delivered every 2 minutes during the stimulation session). Stimulation was delivered (using a wireless activator) for two 30 minute sessions per day while in prone or side lying position. All patients had same visit schedule and interaction during programming and had undergone physical therapy with on average 31 sessions.

120 days (for blinded phase of study);

1 and 2 years (after unblinding for combined cohort).

Mainstay Medical sponsored and contributed to the study, and investigators were paid directly or indirectly (received consultancy fees and research grants from Mainstay Medical, as well as from other medical companies). One author reports receiving stock options from Mainstay Medical.

Baseline (n=204)

mean ± SD

Therapeutic stimulation

% (n=100)

Sham control stimulation

% (n=101)

Difference between groups (95% CI)

P value

Proportion of patients with an improvement in LBP-VAS of ≥30% and no increase in analgesics (Responders ITT, % (n)

57.1%

46.6%

10.4 (-3.3, 24.1)

0.138

Cumulative proportion of responders (analysis of primary outcome data)

N=102

N=102

NA

0.0499

Average LBP VAS (cm)*

7.3±0.7

4.0±2.7

4.8±2.9

Change in average LBP VAS from baseline cm)

-3.3±2.7

-2.4±2.9

-0.9 (-1.6, -0.1)

0.032

Change in VAS from baseline (%)

-44.6±36.8

-33.3±40.8

-11.2 (0.4, 22.0)

0.042

Mean Oswestry Disability Index (ODI), points^^

39.1±10.3

22.3±14.5

25.7±15.0

Change in ODI from baseline

-17.5±15.1

-12.2±14.6

-5.4 (-9.5, -1.2)

0.011

Change in ODI from baseline (%)

-43.0±34.3

-31.2±38.2

-11.8 (-21.9, -1.7)

0.022

Mean EQ-5D index**

0.585±0.174

0.758±0.160

0.713±0.160

Change in EQ-5D from baseline

0.186±0.199

0.115±0.178

0.071 (0.018, 0.123)

0.009

Mean percent pain relief (%)

51.7±32.3

35.0±35.8

16.8 (7.3, 26.3

<0.001

proportion of patients for whom SGIC was "better" or "much better"

54% (54/100)

33.7% (34/101)

20.3% (6.9, 33.8)

0.004

proportions of patients for whom clinical global impression [CGI] was "much better"

57 (57/100)

22 (22/100)

35 (22.3, 47.7)

<0.001

proportion of LBP resolution (VAS≤2.5cm)

34 (34/100)

27.7 (28/101)

6.3 (-6.5, 19)

0.335

Patient satisfaction (TSQ was "definitely satisfied")

61 (61/100)

39.6 (40/101)

21.4 (7.9, 34.9)

0.002

Average LBP VAS (cm)

Treatment group

Sham group

Blinded phase

Baseline

7.3±0.7 (n=102)

7.2±0.7 (n=102)

14 days

5.3* (n=101)

5.4* (n=101)

45 days

4.6* (n=99)

4.7* (n=101)

75 days

4.3* (n=99)

4.6* (n=100)

120 days

4.0±2.7 (n=100)

4.8±2.9 (n=101)

Unblinded phase

Treatment group

Crossover group

180 days

3.6* (n=96)

3.8* (n=93)

240 days

3.2* (n=91)

3.6* (n=93)

360 days

3.1* (n=87)

2.9* (n=89)

Improvement in LBP-VAS at 120 days with no increase in analgesics (%)

Cumulative proportion of participants (%)*

Therapeutic stimulation (n=102)

Sham stimulation (n=102)

≥-40

98

96

≥-30

97

95

≥-20

97

94

≥-10

94

89

≥0

89

78

≥10

81

63

≥20

70

52

≥30

57

47

≥40

51

40

≥50

43

34

≥60

35

31

≥70

28

24

≥80

24

19

≥90

16

11

Mean ± SD at baseline (n =204)

6 months (n =190)

1 year (n = 176)

2 years (n =156)

VAS

Mean LBP VAS (cm)

7.3 ± 0.7

3.7 (0.2)

3.0 (0.2)

2.4 (0.2)

Change in mean VAS (cm)

-

-3.6 (0.2)

(-3.9, -3.3)

-4.3 (0.2)

(-4.7, -3.9)

-4.8 (0.2)

(-4.6, -3.8)

Change in mean VAS (%)

-

-48.6 (2.7)

(-53.9, -43.3)

-58.9 (2.6)

(-64.1, -53.6)

-66.7 (2.6)

(-71.7, -61.6)

≥30% improvement in mean VAS (%)

-

66.1 (125/189)

(59.4, 72.9)

73.9 (130/176)

(67.4, 80.4)

82.6 (128/155)

(76.6, 88.6)

≥50% improvement in mean VAS (%)

-

52.9 (100/189)

(45.8, 60.0)

63.6 (112/176)

(56.5, 70.7)

71.6 (111/155)

(64.5, 78.7)

≥70% improvement in VAS (%)

-

33.9 (64/189)

(27.1, 40.6)

46.6 (82/176)

(39.2, 54.0)

61.9 (96/155)

(54.3, 69.6)

LBP resolution (VAS ≤ 2.5 cm)

-

39.2 (74/189)

(32.2, 46.1)

51.7 (91/176)

(44.3, 59.1)

66.5 (103/155)

(59.0, 73.9)

ODI

Mean ODI

39.1 ± 10.3

21.9 (1.1)

19.0 (1.4)

17.6 (1.2)

Change in ODI (SE)

-

-17.0 (1.1)

(-19.2, -14.8)

-19.9 (1.2)

(-22.3, -17.6)

-21.4 (1.3)

(-24.0, -18.7)

Change in ODI (%)

-

-43.0 (2.8)

(-48.5, -37.4)

-50.5 (2.9)

(-56.3, -44.8)

-54.3 (3.2)

(-60.6, -48.0)

≥20 Pt. improvement in ODI (%)

-

48.1 (91/189)

(41.0, 55.3)

57.4 (101/176)

(50.1, 64.7)

61.3 (95/155)

(53.6, 69.0)

Composite of VAS and ODI

≥50% improvement in mean VAS

and/or ≥20 Pt. ODI

-

63.5 (120/189)

(56.6, 70.4)

73.3 (129/176)

(66.8, 79.8)

77.3 (119/154)

(70.7, 83.9)

≥50% improvement in VAS and

≥20 Pt. ODI

-

37.8 (71/188)

(30.8, 44.7)

47.7 (84/176)

(40.3, 55.1)

56.5 (87/154)

(48.7, 64.3)

EQ-5D-5L index

0.585 ± 0.174

0.765 (0.010)

0.780 (0.012)

0.798 (0.013)

Change in EQ-5D-5L index

-

0.180 (0.014)

(0.153, 0.207)

0.195 (0.016)

(0.167, 0.229)

0.213 (0.017)

(0.184, 0.253)

PPR (%)

-

55.0 (2.5)

(50.1, 59.9)

65.7 (2.4)

(60.9, 70.5)

72.1 (2.4)

(67.3, 77.0)

SGIC "Better" or "Much better"

-

57.4 (109/190)

(50.3, 64.4)

71.6 (126/176)

(64.9, 78.3)

78.6 (121/154)

(72.1, 85.1)

TSQ "Definitely satisfied"

-

64.7 (123/190)

(57.9, 71.5)

78.2 (136/174)

(72.0, 84.3)

80.0 (124/155)

(73.7, 86.3)

CGI "Much better

-

56.8 (108/190)

(49.8, 63.9)

73.3 (129/176)

(66.8, 79.8)

77.6 (118/152)

(71.7, 84.3)

Mean ± SD at baseline (n =204)

6 months (n =204)

1 year (n = 204)

2 years (n =204)

VAS

Mean LBP VAS (cm)

7.3 ± 0.7

3.9 (0.2)

3.4 (0.2)

3.1 (0.2)

Change in mean VAS (cm)

-

-3.4 (0.2)

(-3.8, -3.1)

-3.9 (0.2)

(-4.3, -3.6)

-4.2 (0.2)

(-4.6, -3.8)

Change in mean VAS (%)

-

-47.1 (2.6)

(-52.3, -41.9)

54.3 (2.7)

(-59.5, -49.0)

-58.1 (2.7)

(-63.4, -52.8)

≥30% improvement in mean VAS (%)

-

63.2 (3.5)

(56.5, 70.0)

66.9 (3.4)

(60.3, 73.6)

71.6 (3.3)

(65.1, 78.1)

≥50% improvement in mean VAS (%)

-

51.0 (3.6)

(44.0, 58.0)

58.0 (3.5)

(51.1, 65.0)

62.1 (3.5)

(55.1, 69.0)

≥70% improvement in VAS (%)

-

33.2 (3.4)

(26.5, 39.9)

43.0 (3.6)

(36.1, 50.0)

54.3 (3.7)

(47.1, 61.5)

LBP resolution (VAS ≤ 2.5 cm)

-

38.3 (3.5)

(31.4, 45.1)

47.7 (3.5)

(40.7, 54.6)

57.6 (3.6)

(50.5, 64.7)

ODI

Mean ODI

39.1 ± 10.3

22.7 (1.0)

20.7 (1.0)

20.2 (1.0)

Change in ODI (SE)

-

-16.4 (1.0)

(-18.4, -14.4)

-18.4 (1.0)

(-20.4, -16.4)

-18.9 (1.0)

(-21.0, -16.8)

Change in ODI (%)

-

-41.5 (2.7)

(-46.8, -36.1)

-46.4 (2.8)

(-51.8, -41.0)

-47.5 (2.8)

(-53.0, -42.0)

≥20 Pt. improvement in ODI (%)

-

46.7 (3.5)

(39.8, 53.7)

53.4 (3.5)

(46.5, 60.3)

54.8 (3.6)

(47.7, 61.9)

Composite of VAS and ODI

≥50% improvement in mean VAS

and/or ≥20 Pt. ODI

-

60.4 (3.5)

(53.6, 67.2)

67.4 (3.4)

(60.8, 74.0)

67.4 (3.5)

(60.4, 74.3)

≥50% improvement in VAS and

≥20 Pt. ODI

-

36.8 (3.4)

(30.0, 43.5)

44.0 (3.6)

(37.0, 51.1)

49.9 (3.6)

(42.8, 57.1)

EQ-5D-5L index

0.585 ± 0.174

0.758 (0.011)

0.762 (0.011)

0.768 (0.011)

Change in EQ-5D-5L index

-

0.173 (0.011)

(0.151, 0.194)

0.177 (0.011)

(0.156, 0.199)

0.183 (0.011)

(0.161, 0.205)

PPR (%)

-

53.3 (2.5)

(48.4, 58.2)

60.7 (2.5)

(55.8, 65.6)

62.3 (2.5)

(57.3, 67.3)

SGIC "Better" or "Much better"

-

55.1 (3.5)

(48.2, 62.0)

65.9 (3.4)

(59.3, 72.5)

68.6 (3.4)

(61.9, 75.2)

TSQ "Definitely satisfied"

-

62.8 (3.4)

(56.0, 69.5)

71.8 (3.2)

(65.5, 78.1)

68.3 (3.4)

(61.6, 75.1)

CGI "Much better

-

55.0 (3.6)

(48.0, 62.0)

67.5 (3.4)

(60.8, 74.1)

66.6 (3.6)

(59.6, 73.7)

Events, n

% (n=patients)

Device and procedure-related serious adverse events (all happened before 120 days)

8

3.9 (8/204)

Infection (resolved after system explant, and antibiotics)

6

2.9 (6/204)

Intra-procedural upper-airway obstruction (resolved)

1

0.5 (1/204)

Non-radicular patch of numbness on thigh (ongoing)

1

0.5 (1/204)

Lead migrations

0

0

Surgical interventions

30

13.2 (27/204)

System removal

19

9.3 (19/204)

Lack of effectiveness

9

4.4 (9/204)

Infection

6

2.9 (6/204)

To facilitate MRI

4

2.0 (4/204)

Revision

10

4.9 (10/204)

Lead replacements

6

2.9 (6/204)

Pulse generator repositioned

4

2.0 (4/204)

Re-implanted system post-infection

1

0.5 (1/204)

Unrelated adverse events

7

3 (7/204)

0-6 months

6-12 months

12-24 months

Number of events

% of patients (n=204)

Number of events

% of patients (n=204)

Number of events

% of patients (n=204)

All device and procedure related SAEs

8

3.9 (8/204)

0

0

0

0

Infection (resolved)

6

2.9 (6/204)

0

0

0

0

Intra-procedural upper airway obstruction

(resolved)

1

0.5 (1/204)

0

0

0

0

Non-radicular patch of numbness on thigh

(ongoing)

1

0.5 (1/204)

0

0

0

0

0-6 months

6-12 months

12-24 months

Number of events

% of patients (n=204)

Number of events

% of patients (n=204)

Number of events

% of patients (n=204)

All surgical interventions*

14

6.4 (13/204)

16

6.8 (14/204)

18

8.8 (18/204)

System removal

All system removal

8

4.4 (9/204)

11

5.4 (11/204)

13

6.4 (13/204)

Reported lack of efficacy

1

0.5 (1/204)

8

3.4 (7/204)

9

3.9 (8/204)

Infection

6

2.9 (6/204)

0

0

0

0

Facilitate MRI

1

0.5 (1/204)

3

1.5 (3/204)

2

1.0 (2/204)

Participant relocation

0

0

0

0

0

0.5 (1/204)

LBP pain relief

0

0

0

0

0

0.5 (1/204)

Re-implant post-infection

1

0.5 (1/204)

0

0

0

0

Revision

All revision

5

2.5 (5/204)

5

2.5 (5/204)

5

2.5 (5/204)

Lead replacement

3

1.5 (3/204)

3

1.5 (3/204)

2.0 (2/204)

Pulse generator repositioning

2

1.0 (2/204)

2

1.0 (2/204)

1

0.5 (1/204)

Prospective case series (ReActiv8-A Study NCT01985230)

Australia, United Kingdom, and Belgium

2014 to 2015

n=53 patients with chronic mechanical low back pain (CMLBP) who have failed conventional therapy and are not candidates for surgery or spinal cord stimulation (SCS).

Duration of back pain: mean 14.3 years

Mean age 44 years; 57% (30/53) female

Inclusion criteria:

Adult patients (aged 18 to 65 years) with predominant chronic low back pain for more than 90 days, with no history of prior surgery or currently indicated for spinal surgery, not eligible for spinal cord stimulation, and with no satisfactory pain relief despite medical management (including at least physical therapy and medication) for 1 year, ODI score 25-60%, NRS 6.0-9.0 at baseline, medications at stable dose 30 days prior to enrolment.

Exclusion criteria:

BMI more than 35, indication for back surgery, leg pain worse than back pain or radiculopathy below the knee, back pain exclusions, diagnosis or correction of scoliosis, neurological deficit, sacroiliac joint pain, oral morphine use, rhizotomy procedure of medial branch below T8 in the prior year, anaesthetic block of medial branch or epidural, steroids for back pain in 30 days, previous back surgery below T8, previous thoracic or lumbar sympathectomy, depression, psycho-social problems.

Implantation with a neurostimulator device (ReActiv8, Mainstay Medical Limited) to simulate the medial branch of the dorsal ramus of the L2 nerve root to elicit episodic contraction of the lumbar multifidus.

In the first 47 patients, leads were placed using the 'lateral' surgical approach and in the last 6 subjects, the approach was modified, and the leads (including any replacements) were placed using the 'midline' surgical approach. This was to reduce mechanical stresses on the leads which were found to be responsible for lead conductor fractures and loss of stimulation. The electrodes were placed at the same anatomical target in both the midline and the lateral approaches.

Devices were activated 2 weeks after implantation and programmed via radio frequency telemetry. Patients used a wireless activator to deliver 2 daily 30-min stimulation sessions with the program cycling through 10 sec of stimulated contractions followed by 20 sec of relaxation.

1 year ; 4 years

Study was sponsored by Mainstay Medical. Authors have also received consultancy fees and research grants from Mainstay Medical, and other medical companies.

Back pain (7 day average NRS)^

7 day average NRS^

6.8±0.8

4.3 ± 2.1

4.6

4.4^^^

4.1^^^

3.5^^^

3.2±0.4^^^

Improvement from baseline–absolute change

-2.5 ± 0.3

(p < 0.0001)

NR

NR

Improvement from baseline–% change

36%

(p < 0.0001)

Responder rate**

58 (30/52)

NR

NR

Back pain (single day NRS)*

Single day NRS

6.8±0.8

4.3 ± 2.2

4.6 ± 2.5

4.4 ± 2.7

Improvement from baseline–absolute change

-2.5 ± 0.3

(p < 0.0001)

-2.2 ± 0.4

(p < 0.0001)

-2.4 ± 0.4

(p < 0.0001)

Improvement from baseline–% change

-35%

-32%

-33%

MCID

>2 point improvement (% of subjects)

63% (33/52)

61% (31/51)

57% (27/47)

Disability on Oswestry Disability Index (ODI)^^

ODI

44.9 ± 10.1

31.3 ± 17.6

32.8 ± 20.3

30.7 ± 19.2

28^^^

26^^^

23.0±3.2^^^

Improvement from baseline–absolute change

-13.4 ± 2.2

(p < 0.0001)

-11.6 ± 2.4

(p < 0.0001)

-14.3 ± 2.3

(p < 0.0001)

MCID

>10 point improvement (% of subjects)***

52% (27/52)

57% (29/51)

60% (28/47)

Quality of life on EQ-5D

0.434 ± 0.185

0.648 ± 0.195

0.622 ± 0.235

0.654 ± 0.217

0.68^^^

0.71^^^

0.721±0.035^^^

Improvement from baseline–absolute change

0.213 ± 0.025

(p < 0.0001)

0.184 ± 0.032

(p < 0.0001)

0.219 ± 0.028

(p < 0.0001)

MCID

>0.03 point improvement (% of subjects)***

88% (46/52)

82% (42/51)

81% (38/47)

Mean improvement in low back pain from NRS baseline (6.8±0.8 for original cohort, 6.7±1.2 for 4-year completed cohort)

Follow-up period

1-year completed case cohort (n=47)

2-year completed case cohort (n=39)

3-year completed case cohort (n=37)

4-year completed case cohort (n=33)

Standard deviation

1 year

2.4

2.6

2.7

2.6

0.14

2 years

-

2.7

2.8

2.8

0.08

3 years

-

-

3.3

3.2

0.10

4 years

-

-

-

3.5

-

Mean improvement in back pain-related disability from ODI baseline (44.9±10.1 for original cohort, 43.8±9.9 for four-year NRS completed cohort)

Follow-up period

1-year completed case cohort (n=47)

2-year completed case cohort (n=39)

3-year completed case cohort (n=35)

4-year completed case cohort (n=32)

Standard deviation

1 year

14.3

16.4

17.4

17.1

1.39

2 years

-

17.0

17.9

18.9

0.95

3 years

-

-

19.7

20.3

0.37

4 years

-

-

-

22.2

-

Mean improvement in quality of life from EQ-5D baseline (0.434±0.185 for original cohort, 0.444±0.186 for four-year NRS completed cohort)

Follow-up period

1-year completed case cohort (n=47)

2-year completed case cohort (n=39)

3-year completed case cohort (n=35)

4-year completed case cohort (n=32)

Standard deviation

1 year

0.219

0.247

0.245

0.235

0.01

2 years

-

0.244

0.256

0.263

0.00

3 years

-

-

0.288

0.286

0.00

4 years

-

-

-

0.285

-

% (n= events)

% (n=patients)

Total adverse events

n=145

Related to procedure, device and/or stimulation (none were serious)^

52% (76/145)

66 (35/53)

Procedure related (wound pain, inflammation, hematoma, postoperative

discomfort)

18 (14/76)

21 (11/53)

Device related (loss of stimulation [23 in 17 patients], pocket/lead discomfort [13 in 12 patients], 3 undesired sensations)

51 (39/76)

47 (25/53)

Device/procedure related (seroma/inflammation because of lead incision, postoperative nervous system irritation)

9 (7/76)

9 (5/53)

Device/stimulation related (undesired sensations in target area, muscle fatigue)

21 (16/76)

29 (15/53)

Lead migration (leading to loss of sensation)

1

1

Unrelated to procedure (3 were serious: surgical removal of uterine fibroid, non-cardiac chest pain, cerebrovascular accident)

48 (69/145)

53 (28/53)

Overall device explantation (within 1 year)

(1 because of lead migration before 90 days follow up, 4 because of lack of efficacy within 1 year)

9.4 (5/53)

Device explantation at 4 years

Device explantation (without clinical benefit)

20.8% (11/53)

Device explantation (with clinical benefit)

7.5% (4/53)

Device explantation because of lead migration

1.9% (1/53)

% (n)

Total device problems*

70 events

Lead conductor fractures because of tight bending [in those implanted using lateral approach]) leading to loss of stimulation, high impedance [>5000 X] post-implantation (on one of the conductor on the stimulation channels).^

53% (28/53)

44 leads

Surgical revision to implant new leads

13

Reprogrammed to resume bilateral stimulation via a different electrode configuration

7

Continued therapy with unilateral stimulation

3

System turned off

3

System explanted

2

Prospective case series (PMCF study)

United Kingdom

Not reported

n=42 patients with chronic mechanical lower back pain (CMLBP) that has not responded to physiotherapy or medication, and with no indications for surgery.

Mean duration of CMLBP: 13.7±10.2 years

Mean age 47.2±11.0 years, 40% female

Inclusion criteria: Adult patients with a history of mechanical CLBP lasting more than 90 days that was refractory to physiotherapy or medication.

Exclusion criteria: Clear indications for surgery, additional clinical conditions with potential impact on therapeutic delivery or assessment of pain relief.

Patients were implanted with a restorative neurostimulation device (ReActiv8).

Devices were activated around 14 days after implantation, and patients used a wireless activator to deliver 2 daily 30-min stimulation sessions while resting in either a prone or lateral position.

2 years

Study was sponsored by Mainstay Medical. Authors have also received consultancy fees and research grants from Mainstay Medical and other medical companies.

Baseline (n=42)

45 days (n=42)

90 days (n=42)

180 days (n=42)

1 year (n=39)

2 years (n=37)

Mean NRS

7.0±0.2

5.6 ± 0.3

5.5 ± 0.4

5.2 ± 0.4

4.7 ± 0.4

3.5 ± 0.3

(p<0.0001)

≥30% improvement in NRS (%)

-

-

33*

45*

49*

67.6 (25/37)

≥50% improvement in NRS (%)

-

-

21*

24*

39*

56.8 (21/37)

Mean ODI

46.2±2.2

-

37*

36*

32*

29.2 ± 3.1

(p<0.0001)

≥15 Pt. improvement in ODI (%)

-

-

24*

33*

41*

51.4 (19/37)

≥20 Pt. improvement in ODI (%)

-

-

14*

26*

31*

43.2 (16/37)

Mean EQ5D

0.426 ± 0.035

-

0.58*

0.57*

0.62*

0.680 ± 0.030

(p<0.0001)

Mean NRS

7.0±0.2

4.9 ± 0.4

4.0 ± 0.4

Mean ODI

46.2±2.2

33*

32*

Mean EQ5D

0.426 ± 0.035

0.60*

0.61*

Event

Number of events

% of patients (n=42)

Number of events resolved

Total adverse events

20

28.6% (12/42)

15/20 (75%)

Overstimulation of tissue

10

16.7% (7/42)

7/10 (70%)

Implant site pocket pain

3

(3/42)

2/3 (66.6%)

Lead conductor fracture

2

(2/42)

2/2 (100%)

Implant site blisters

1

(1/42)

1/1 (100%)

Implant site pocket infection

1

(1/42)

1/1 (100%)

Pain in leg

1

(1/42)

0/1 (0%)

Synovial cyst

1

(1/42)

1/1 (100%)

Wound pain

1

(1/42)

1/1 (100%)

Case series

Belgium and the UK (4 sites)

2011 to 2012

n=28 patients with continuing chronic low back pain (CLBP) despite physical therapy and medication and no prior surgery.

Duration of CLBP: 6.2 years (range 1.2 to 29.6)

Mean age 43.9 years; 62% female (16/26)

Inclusion criteria: patients between 18 to 60 years, with CLBP for more than 90 days, Oswestry Disability Index above 25, refractory to physical therapy and medications; compromised neural drive to the lumbar multifidus on a prone weighted upper extremity lift test (WUELT) determined by a change in thickness of less than 20% of the lumbar multifidus during contraction on the right or left side at L4 or L5.

Exclusion criteria: Patients with BMI above 35, with an indication for surgery or prior back surgery, previous interventions including medial branch rhizotomy, with implanted devices and not suitable for neuromodulation therapies, inability, or unwillingness to comply with study protocol.

Patients were implanted with commercially available implantable neurostimulator (pulse generators) and stimulation leads, positioned adjacent to the medial branch of the dorsal ramus of the spinal nerve as it crosses the L3 transverse process. Once position of the leads is confirmed, they are attached to muscular fascia using suture sleeve partially inserted into the muscle. Episodic electrical stimulation resulted in contraction of the lumbar multifidus (LM) muscle. Patients self-administered stimulation using an external controller, twice daily for 20 minutes.

3 and 5 months

Authors have served as speakers, consultants, or advisory board members for the company (Mainstay Medical), and 3 were employed by them.

Average low back pain (VAS, mm)

67.3±11.1

40.8 ± 23.8

26.4±22.3

(p<0.0001)

73.7 (14/19)

39.7 ± 33.4

(n=18)

27.6±27.3

(p=0.0005)

66.7 (12/18)

Disability (ODI)

38.5±14.6

27.6 ± 15.6

10.9 ±9.6

(p=0.0001)

63.2 (12/19)^

29.6 ± 29.3 (n=19)

12.1±14.4

(=0.0017)

52.6 (10/19)

Quality of life (EQ-5D)^^

0.43±0.34

0.70 ± 0.21

0.27±0.24

(p=0.0002)

0.20±0.43

(p=0.06)

Adverse events

% (n)

No of events

Total adverse events

97

Related to device and/or procedure

74 (20/27)

60

Procedure related

13

Device related

27

Both device and procedure related

20

Unrelated to device or procedure

37

Adverse events

Lead migration (leading to inadequate stimulation or surgical revision)*

48.1 (13/27)^

21

Inadequate stimulation (lead migration in 8, high impedance in 2, pulse generator malfunction in 2, reason not specified in 1)

48.1 (13/27)

13

Pain

14.8 (4/27)

8

Over stimulation

11.1 (3/27)

5

Undesired sensations (target/non-target area)

7.4 (2/27)

2

Tissue injury

3.7 (1/27)

1

Fever

3.7 (1)

1

Abnormal healing

3.7 (1/27)

1

Nausea or vomiting (related to anaesthesia)

3.7 (1/27)

1

Nervous system irritation/injury

3.7 (1/27)

2

Musculoskeletal fitness

7.4 (2/27)

2

Infection (needed device removal)

3.7 (1/27)

1

Seroma

3.7 (1/27)

1

Risk with any surgical procedure

3.7 (1/27)

1

Surgical revisions and device explant

20

Lead migration (11 repositioned, 1 explanted)

37.0 (10/27)

12

High impedance

7.4 (2/27)

2

IPG migration

7.4 (2/27)

2

IPG failure

3.7 (1/27)

1

Discomfort because of lead anchor

7.4 (2/27)

2

Explant (because of infection and lead migration)

3.7 (1/27)

1