Evaluation of pulsed electromagnetic field therapy for the treatment of chronic postoperative pain following lumbar surgery: a pilot, double-blind, randomized, sham-controlled clinical trial

Figures & data

Table 1 Key inclusion and exclusion criteria

Inclusion criteria

Exclusion criteria

• Age ≥22 years • One or two anatomically successful lumbar back surgeries for the treatment of low back pain • Persistent pain in the low back and/or radiating to leg(s) for ≥3 months and ≤36 months following the most recent surgery • Stable analgesic dosing regimen (including opioid and nonopioid medication) for ≥30 days prior to the Screening Visit • Mean pain intensity ≥3 and <9 as measured on the numeric pain rating scale during the 10-day run-in period • Completion of a minimum of 80% of the ePRO diary assessments during the 10-day run-in period

• History of more than two lumbar spine surgeries • Required additional lumbar surgery or surgery of any type prior to Day 75 • Disc fusion at any level in the most recent surgery • Any local injection into the lumbar spine within 30 days prior to the Screening Visit or within 6 weeks prior to the Screening Visit with long-acting lidocaine injection products • Use of systemic corticosteroids within 2 months of the Screening Visit • History of an ongoing painful condition that, in the opinion of the investigator, might have had a confounding influence on the safety or effectiveness analysis • Implanted pacemaker, defibrillator, neurostimulator, spinal cord stimulator, bone stimulator, cochlear implant, or other implanted device with an implanted metal lead(s) • Consumption of an average of >100 mg oral morphine sulfate equivalents per day during the 10-day run-in period • SD around the mean of the mean PI scores during the 10-day run-in period was >2.0 • BMI >38 kg/m^2 • Previous treatment with the PEMF therapy

Abbreviations: PI, pain intensity; BMI, body mass index; PEMF, pulsed electromagnetic field; ePRO, electronic patient-reported outcome.

Figure 1 Study flow chart and patient profile.

Abbreviations: n, number of subjects; PEMF, pulsed electromagnetic field.

Table 2 Subject demographics and baseline characteristics

	Sham	38-µs group	42-µs group	p-value
Gender, n (%)				0.46
Male	5 (36.0)	7 (50.0)	8 (62.0)
Female	9 (64.0)	7 (50.0)	5 (36.0)
Age (years)	50.6 (12.2)	51.2 (12.3)	56.0 (14.3)	0.59
Height (cm)	170 (12.2)	173 (15.7)	169 (10.7)	0.69
Weight (kg)	85 (19.3)	86.2 (22.5)	87.5 (13.7)	0.94
BMI (kg/m^2)	29.3 (5.1)	28.6 (5.8)	30.7 (4.5)	0.56
Time since surgery (months)	15.1 (10.4)	12.6 (8.6)	12.7 (7.6)	0.70
PI, lumbar	5.1 (1.0)	5.5 (1.6)	4.9 (1.9)	0.41
PI, radiating leg	4.3 (1.8)	5.4 (1.6)	5.1 (1.8)	0.83
ODI	33.8 (14.7)	39.7 (17.9)	32.4 (9.6)	0.48
BDI (units)	10.1 (6.74)	12.4 (5.57)	9.7 (6.55)	0.80
hsCRP (mg/L)	2.3 (2.1)	2.1 (2.6)	0.56	0.5857

Note: Data are reported for ITT population/and recorded as mean (±SD) unless otherwise specified.

Abbreviations: n, number of subjects; PI, pain intensity; ODI, Oswestry Disability Index; BDI, Beck Depression Inventory; hsCRP, high-sensitivity C-reactive protein; ITT, intent-to-treat; BMI, body mass index.

Figure 2 Mean pain scores at the end of treatment (Days 56–60) compared with baseline.

Notes: (A) Lumbar pain. (B) Radiating leg pain. Statistical analyses were conducted using one-way analysis of variance and show the within-group p-values.
Abbreviation: NPRS, numerical pain rating scale.

Figure 3 Mean pain scores over time.

Notes: (A) Lumbar pain. (B) Radiating Leg pain. Mean pain scores are for consecutive 5-day intervals throughout the study.
Abbreviations: NPRS, numerical pain rating scale; PEMF, pulsed electromagnetic field.

Figure 4 Mean pain scores over time normalized to baseline.

Notes: (A) Lumbar pain. (B) Radiating Leg pain. For each study group, the mean pain scores were normalized to baseline pain scores, and plotted as a percentage of baseline. Average pain scores are for consecutive 5-day intervals throughout the study. For each study group, data are expressed as a percentage of the mean baseline pain score for that study group.
Abbreviation: PEMF, pulsed electromagnetic field.

Table 3 Primary outcome measure at 60 days

	Sham group (n = 14)	38-µs group (n = 14)	42-µs group (n = 10)
Subjects completed study, n	13	13	9
Compliance, hours (±SD)	46.7 (16.96)	49.7 (14.51)	57.2 (4.38)
Lumbar NPRS, mean PI, baseline, Day 0 (SD)	5.1 (0.96)	5.5 (1.79)	4.9 (1.94)
Lumbar NPRS, mean PI, end of treatment, Day 60 (SD)	3.8 (1.58)	4.2 (1.63)	2.9 (1.66)
Lumbar mean PI, absolute mean change	−1.3	−1.3	−2
Lumbar % change from baseline in mean PI at Day 60 (SD)	−25.6 (24.81)	−18.6 (39.47)	−40.2 (26.35)
Lumbar mean PI 95% CI	(39.1, −12.1)	(−40.1, 2.9)	(−57.4, −23.0)
	(n = 12)	(n = 10)	(n = 8)
Radiating leg NPRS, mean PI, baseline, Day 0 (SD)	4.3 (1.78)	5.4 (1.6)	5.1 (1.83)
Radiating leg NPRS, mean PI, end of treatment, Day 60 (SD)	3.3 (2.29)	4.3 (1.6)	2.8 (1.60)
Radiating leg mean PI, absolute mean change	−1	−1.1	−2.3
Radiating leg % change from baseline in mean PI at Day 60 (SD)	−24.5 (33.79)	−17.0 (31.15)	−45.0 (29.39)
Radiating leg mean PI 95% CI	(−44.5, −4.5)	(−36.3, 2.3)	(−65.4, −24.6)

Abbreviations: PI, pain intensity; NPRS, numerical pain rating scale.

Table 4 Secondary outcome measures at 60 days

	Sham group	38-µs group	42-µs group
Responder analysis: percentage of patients with a 30% reduction in NPRS (Days 56–60)	(n = 13)	(n = 13)	(n = 9)
Lumbar (% of n)
30% change in mean PI (%)	30.77	46.15	55.56
30% change in worst PI (%)	23.08	38.46	55.56
Radiating leg (% of n)	(n = 12)	(n = 10)	(n = 8)
30% change in mean PI (%)	41.67	40.00	50.00
30% change in worst PI (%)	41.67	40.00	37.50
Percentage change from baseline in worst PI (n)	(n = 13)	(n = 13)	(n = 9)
Lumbar NPRS, worst PI, baseline, Day 0 (SD)	6.5 (1.43)	7.0 (1.75)	6.3 (1.46)
Lumbar NPRS, worst PI, end of treatment, Day 60 (SD)	5.4 (1.93)	5.7 (2.39)	4.3 (2.28)
Lumbar worst PI mean change	−1.1	−1.3	−2
Lumbar % change from baseline in worst PI at Day 60 (SD)	−17.9 (24.22)	−19.6 (24.35)	−33.8 (31.89)
Lumbar worst PI 95% CI	(−31.1, −4.7)	(−32.8, −6.4)	(−54.6, −13.0)
	(n = 12)	(n = 10)	(n = 8)
Radiating leg NPRS, worst PI, baseline, Day 0 (SD)	5.9 (2.38)	6.5 (1.98)	6.5 (1.64)
Radiating leg NPRS, worst PI, end of treatment, Day 60 (SD)	4.9 (3.00)	5.3 (2.05)	4.4 (1.73)
Radiating leg worst PI mean change	−1	−1.2	−2.1
Radiating leg % change from baseline in worst PI at Day 60 (SD)	−19.2 (37.07)	−14.6 (36.45)	−29.5 (27.57)
Radiating leg worst PI 95% CI	(−41.1, 2.7)	(−37.2, 8.0)	(−48.6, −10.4)
Oswestry Disability Index	(n = 13)	(n = 13)	(n = 10)
Mean baseline (SD)	33.8 (14.73)	39.7 (17.94)	32.4 (9.65)
Mean visit Day 61 (SD)	28.8 (13.85)	33.1 (18.97)	27.0 (13.64)
Percentage difference (95% CI)	−14.9 (−24.9, −4.9)	−17.7 (−33.5, −1.9)	−15.2 (−42.0, 11.6)
Beck Depression Inventory (responders with >5 point decrease)	23.08%	30.77%	10%
hsCRP levels (mg/L)	(n = 13)	(n = 11)	(n = 9)
Baseline (SD)	2.3 (2.11)	2.1 (2.59)	3.2 (2.72)
Day 61 (SD)	4.5 (6.27)	2.8 (2.60)	2.7 (2.32)
Difference (95% CI)	2.2 (−1.3, 5.7)	0.7 (−0.4, 1.8)	−0.5 (−1.8, 0.8)
Patient global impression of change (% patients, Day 60)
Minimally worse	0 (0.0)	1 (11.1)	0 (0.0)
No change	5 (45.5)	4 (44.4)	2 (25.0)
Minimally improved	4 (40.0)	2 (22.2)	3 (37.5)
Much improved	1 (9.1)	2 (22.2)	3 (37.5)
Very much improved	1 (9.1)	0 (0.0)	0 (0.0)
Time to 30% decrease in mean PI, days	(n = 14)	(n = 14)	(n = 12)
Lumbar (95% CI)	22.0 (12.00, 41.00)	19.00 (6.00, 32.00)	8.00 (6.00, 32.00)
Radiating leg (95% CI)	10.00 (1.00, 23.00)	16.00 (2.00, 36.00)	6.00 (3.00, 14.00)
Time to 30% decrease in worst PI, days	(n = 14)	(n = 14)	(n = 12)
Lumbar (95% CI)	22.0 (3.00, 55.00)	17.00 (8.00, 25.00)	8.00 (3.00, 21.00)
Radiating leg (95% CI)	20.00 (2.00, 43.00)	32.00 (3.00, 32.00)	9.00 (1.00, 30.00)
Post hoc analysis-pain (AUC)	(n = 14)	(n = 14)	(n = 12)
Lumbar mean integrated pain (SD)	246.9 (74.07)	251.4 (120.86)	186.5 (84.17)
(95% CI)	(208.1, 285.7)	(188.1, 314.7)	(138.9, 234.1)
Lumbar mean integrated change from baseline (SD)	−45.1 (54.03)	−50.7 (71.38)	−56.8 (88.80)
(95% CI)	(−73.4, −16.8)	(−88.1, −13.3)	(−107.0, −6.6)
Radiating leg mean integrated pain (SD)	215.1 (101.05)	238.1 (126.62)	173.5 (70.77)
(95% CI)	(160.2, 270.0)	(163.3, 312.9)	(131.7, 215.3)
Radiating leg mean integrated change from baseline (SD)	−29.4 (55.67)	−48.2 (86.28)	−69.7 (91.10)
(95% CI)	(−59.7, 0.9)	(−99.2, 2.8)	(−123.5, −15.9)

Notes: Data reported as mean ± SD (device usage, end-of-treatment PI and ODI scores, end-of-treatment hsCRP levels, % change in PI), mean with 95% CIs (time to 30% decrease in PI, % change in ODI, change in hsCRP), percentage of subjects analyzed (responder analyses, PGIC, BDI), and mean AUC score with percentage change from baseline (post hoc AUC). Summary statistics reported are for the PP population, except for time to 30% decrease in PI and AUC analyses, which are reported for the ITT population. For PP population analyses, only subjects reporting data at end of treatment were included in the analysis. Some subjects reported only lumbar or radial pain. Data for all of these subjects are included in the summary statistics for lumbar and radiating leg PI scores reported. For percentage change from baseline for PI, AUC, and ODI, improvement is denoted by a negative value. For baseline scores, see Table 4. For all analyses using PI scores, mean PI scores were used. End-of-treatment PI scores refers to the average of scores for Days 56–60. End of treatment for ODI and hsCRP refers to the Day 61 Interim Visit. PGIC data are reported for Day 60. BDI data are reported for Day 60.

Abbreviations: PI, pain intensity; AUC, area under the curve; ODI, Oswestry Disability Index; PGIC, Patient Global Impression of Change; BDI, Beck Depression Inventory; hsCRP, high-sensitivity C-reactive protein; n, number of subjects; PP, per protocol.

Figure 5 Time to 30% reduction in pain score is the time to response. Figures show the time to 30% reduction, which was evaluated using Kaplan–Meier statistics.

Notes: (A) Lumbar pain, median time to response-Interval 5 (21–25 days) for 42 µs and Interval 9 (41–45 days) for sham (p = 0.33, log-rank test). (B) Radiating leg pain, median time to response-Interval 5 (21–25 days) for 42 µs and Interval 13 (61–65 days) for sham (p = 0.32, log-rank test).

Table S1 Titles of participating sites:

01 – AOC Research, Birmingham, AL, USA [Dr R Sorrell]

02 – Injury Care, Boise, ID, USA [Dr R Radnovich]

03 – Danville Orthopedic Clinic, Danville, VA, USA [Dr L Abram]

04 – Upstate Clinical Trials, Spartanburg, SC, USA [Dr Y Mironer]

05 – Coastal Orthopedics, Bradenton, FL, USA [Dr R Bundschu]

06 – Tarheel Clinical Research, Raleigh, NC, USA [Dr W Harper]

07 – Millennium Pain Center, Bloomington, IL, USA [Dr R Benyamin]

08 – HOPE Research Institute, Phoenix, AZ, USA [Dr M Doust]

09 – HOPE Research Institute, Las Vegas, NV, USA [Dr W Le]

10 – Navarro Research Group, Chula Vista, CA, USA [Dr R Navarro]

11 – Washington Center for Pain Management, Everett, WA, USA [Dr P Mambalam]

12 – Physicians’ Research Options (PRO), Sandy, UT, USA [Dr A Krull]

13 – Physicians’ Research Options (PRO), Las Vegas, NV, USA [Dr W Muir]