Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial

Abstract

Objective: The PROCO RCT is a multicenter, double-blind, crossover, randomized controlled trial (RCT) that investigated the effects of rate on analgesia in kilohertz frequency (1-10 kHz) spinal cord stimulation (SCS).

Materials and methods: Patients were implanted with SCS systems and underwent an eight-week search to identify the best location ("sweet spot") of stimulation at 10 kHz within the searched region (T8-T11). An electronic diary (e-diary) prompted patients for pain scores three times per day. Patients who responded to 10 kHz per e-diary numeric rating scale (ED-NRS) pain scores proceeded to double-blind rate randomization. Patients received 1, 4, 7, and 10 kHz SCS at the same sweet spot found for 10 kHz in randomized order (four weeks at each frequency). For each frequency, pulse width and amplitude were titrated to optimize therapy.

Results: All frequencies provided equivalent pain relief as measured by ED-NRS (p ≤ 0.002). However, mean charge per second differed across frequencies, with 1 kHz SCS requiring 60-70% less charge than higher frequencies (p ≤ 0.0002).

Conclusions: The PROCO RCT provides Level I evidence for equivalent pain relief from 1 to 10 kHz with appropriate titration of pulse width and amplitude. 1 kHz required significantly less charge than higher frequencies.

Keywords: Chronic pain; PROCO; double-blind; high frequency; high frequency SCS; kilohertz SCS; randomized controlled trial; sub-perception SCS.

Figure 1

Study design. Patients followed standard of care (green) until rate randomization when they experienced four different frequencies. After rate randomization, the best rate was selected for three month follow‐up.

Figure 2

Patient flowchart.

Figure 3

Pain relief and charge required across frequencies. Error bars denote standard error. a. Back pain. b. Leg pain. c. Overall pain. d. Mean charge per second. ***p ≤ 0.001, ***** p ≤ 0.00001.

Figure 4

Quality of life metrics across frequencies. Error bars denote SEM. a. ODI summary score. b. EQ‐5D‐5L summary score. c. PSQI total score. d. PGIC.

Figure 5

Pain relief three months after completion of rate randomization and rate selected for three month follow‐up. a. Back pain. b. Leg pain. c. Overall pain. d. Distribution of rates selected for three month follow‐up.

Figure 6

Comparison of variance in ED‐NRS during titration and three month follow‐up. Each symbol represents one patient's variance during titration (ED‐NRS Var_titration) divided by variance during the three month follow‐up (ED‐NRS Var_{3 month follow‐up}). The patients are ordered in increasing ratio of ED‐NRS Var_titration to ED‐NRS Var_{3 month follow‐up}. Seventeen of 20 patients had larger variance in ED‐NRS during titration, indicating that ED‐NRS was more stable on the optimal setting used during three month follow‐up.

Figure 7

Comparison of responder rate during trial using in‐clinic assessment and ED‐NRS. While the responder rate based on in‐clinic verbal report was 97% (33/34), the responder rate for the same patients based on ED‐NRS was 62% (21/34).