HF-Stimulation: Aktuelle Studienlage und eigene Ergebnisse J.Kraschl 1, M.C. Spendel 1 1 Klinikum Klagenfurt am Wörthersee
Disclosures No disclosures
Agenda Einleitung Derzeitige Studienlage SENZA-Studie Eigene Daten Diskussion Fazit
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Einleitung Traditionelles SCS HF 10 Therapie Ziel ist die Überdeckung der Schmerzareale mit Paresthesien Elektroden meist Höhe TH6- TH10 ( Leg und Back Pain) Implantation erfordert intraoperative Patientenmitarbeit Paresthesia mapping ist nicht erforderlich Elektroden an anatomischer Position ( TH8-TH11) intraoperative Patientenmitarbeit nicht erforderlich
Studienlage Study System Patient Schultz 2012 Medtronic Restore Sensor Predom Leg Pain Study System Patient North 2005 Kumar 2008 Medtronic Itrel Medtronic Synergy Predom Leg Pain Predom Leg Pain Leg Pain (VAS, Response, N) Back Pain (VAS, Response, N) Trial Leg Pain (VAS, Response, N) Back Pain (VAS, Response, N) Success Base 6m 12m 24m Base 6m 12m 24m Trial Success Base 6m 12m 24m Base 6m 12m 24m NA 17/24 71% VAS 5.9 4.3 NR NR NR NR NR NR Response NR NR NR NR NR NR NR N 76 71 NR NR NR NR NR NR VAS NR NR NR NR NR NR NR NR Response NR NR 47% NR NR NR NR N 24 24 NR 19 NR NR NR NR 43/52 VAS 7.6 4 4.4 4.4 5.5 4.1 4.5 4.8 83% Response 48% 38% 40% NR NR NR N 52 50 42 42 52 50 42 42
SENZA-Studie COMPARATIVE, FEASIBILITY 5 centers, 24 patients trialed with both traditional SCS and HF10 therapy Demonstrated safety and efficacy in humans (acute follow-up) 88% of patients preferred highfrequency SCS Published in Neuromodulation 2009 U.S. Feasibility Study PROSPECTIVE, LONG-TERM 2 centers, 72 patients implanted Demonstrated long-term safety and efficacy for both back pain and leg pain (24-month followup) Published in Pain Medicine 2013 EUROPEAN MULTICENTER, 24-MONTH STUDY (SENZA-EU) RANDOMIZED, CONTROLLED 10 U.S. centers, 241 enrolled, 198 randomized, 171 implanted Randomized, controlled trial compared HF10 therapy with traditional SCS Demonstrated superiority at all primary and secondary endpoints vs. traditional SCS (24-month follow-up) Published in Anesthesiology and Neurosurgery 2015 U.S. PIVOTAL STUDY (SENZA-RCT)
SENZA-Studie SENZA-RCT (registered in ClinicalTrials.gov - NCT01609972) Traditionelle SCS HF 10 Therapie Boston Scientific Precision Plus system delivering traditional SCS (2-1200 Hz) Nevro Senza SCS system delivering HF10 therapy (10 khz stimulation)
SENZA-Studie Characteristics Gender n (%) Test (HF10 therapy) Control (Traditional SCS) Female 57 (62.0%) 51 (58.6%) Male 35 (38.0%) 36 (41.4%) Age (years) at Enrollment Mean ± SD 54.6 ± 12.4 55.2 ± 13.4 Range 32.8 to 82.2 19.2 to 82.3 Years Since Diagnosis Mean ± SD 13.0 ± 10.4 14.2 ± 12.2 Range 1.0 to 52.0 1.0 to 62.0 Previous Back Surgery n (%) 80 (87.0%) 75 (86.2%) Baseline Use of Opioids n (%) 83 (90.2%) 75 (86.2%)
SENZA-Studie 241 Participants Assessed for Eligibility 198 Randomized 43 Excluded (43 Screen Failures) 101 Assigned to HF10 therapy 97 trialed with SCS system 90 successful SCS trial 7 unsuccessful SCS trial 4 not trialed 2 medical contraindication 1 withdrew consent 1 lost to follow-up 97 Assigned to traditional SCS 92 trialed with SCS system 81 successful SCS trial 11 unsuccessful SCS trial 5 not trialed 4 withdrew consent 1 medical contraindication 90 reported at 12 months 81 reported at 12 months 85 included through 24 months 4 not included in 24 month analysis 1 withdrew consent 1 required an MRI 1 death 1 lost to follow-up 71 included through 24 months 9 not included in 24 month analysis 4 lost to follow-up 2 death 2 did not consent to the study extension 1 required an MRI
SENZA-Studie Test (HF10 therapy) Control (Traditional) Month 3 Month 12 Month 3 Month 12 Frequency Hz Minimum mean ± SD 10,000 10,000 39.3 ± 14.2 39.2 ± 15.0 Maximum mean ± SD 10,000 10,000 77.3 ± 133.5 66.4 ± 43.6 Amplitude ma Minimum mean ± SD 1.6 ± 1.1 2.0 ± 0.7 3.7 ± 2.7 3.9 ± 3.0 Maximum mean ± SD 3.4 ± 0.7 3.4 ± 1.0 7.7 ± 3.7 8.5 ± 4.0 Pulse width µs Minimum mean ± SD 30.0 30.0 363.4 ± 146.1 346.5 ± 148.4 Maximum mean ± SD 30.0 30.0 575.3 ± 216.2 591.3 ± 214.0
SENZA-Studie Adverse Events HF10 therapy (n=101) Traditionelles SCS (n=97) Lokale Schmerzen 10(9.9%) 10(10.3%) Störende Paresthesien 0 (0.0%) 11(11.3%) Elektrodendislokation 3(3.0%) 5(5.2%)
VAS (cm) SENZA-Studie Back Pain 10 9 8 7 HF10 Therapie Traditionelles SCS 6 5 4.5 41% 4 3 2 1 2.4 67% 0 0 3 6 9 12 15 18 21 24 Untersuchung (mo)
VAS (cm) SENZA-Studie Leg Pain 10 9 8 7 6 HF10 Therapie Traditionelles SCS 5 4 3.9 46% 3 2 1 2.4 65% 0 0 3 6 9 12 15 18 21 24 Untersuchung (mo) P=0.027
SENZA-Studie Back Pain Responderrate 76% 49% Leg Pain Responderrate 73% 49% p<0.001 p<0.003
SENZA-Studie HF10 Therapie Traditionelles SCS 2.5 VAS Back Pain Pat. [%] Pat. [%] 100% p=0.001 100% 2.5 VAS Leg Pain p=0.001 75% 68.5% 65.9% 75% 67.4% 65.9% 50% 25% 36.3% 31.0% 50% 25% 42.5% 39.4% 0% 12 24 Auswertung (m) 0% 12 24 Auswertung (m) 2/3 der implantierten Patienten zeigte eine sehr gute Langzeitwirkung mit HF10 Therapie
% Pat. ODI Level SENZA-Studie Langzeiteffekt 100% 80% 60% 40% 20% 39% 49% 41% 65% 10% 24% Baseline 24 months Baseline 24 months CONTROL (TRADITIONELLES SCS) TEST (HF10 THERAPIE) Crippled Severe Moderate Minimal P=0.015 ODI = Oswestry Disability Index
Eigene Daten n=28 SCS Kein SCS
Eigene Daten Andere 20% Back Pain 27% Back + Leg Pain 53%
Eigene Daten Responderrate Trial Dauer [%] 90% [d] 25 80% 70% 20 60% 50% 81% 15 20 d 40% 30% 10 20% 10% 5 0% Trail Success Rate 0 Tage (median)
Diskussion Schmerzbesserung bei bisherigen prospektiven SCS Studien 1. Al-Kaisy A, et. al. Sustained effectiveness of 10 khz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study. Pain Med. 2014;15:347-354. 2. Kapural, Leonardo et. al. Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology Vol. 123 No 4. October 2015. 3. Kumar, K. The effects of spinal cord stimulation in neuropathic pain are sustained: A 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery 2008. 4. Pope, J. Clinical Evidence: Burst. Presented at NANS-NIC Congress, June 25, 2016.
Diskussion SCS Studien Große prospektive & veröffentlichte Studien nach Waveform Technology Key Studies Key Findings Traditionelles SCS (40-60 Hz) HF10 Therapie Burst Waveforms Experimentelle Waveforms (High Density, 1,000-1,200 Hz) North (2005) Kumar: PROCESS (2008) Schultz (2012) Kapural: SENZA-EU (2014) Kapural: SENZA-RCT (12-month: 2014, 24-month: 2016) SUNBURST (Unpublished, presented NANS 2015) No prospective, published evidence SCS zeigt eine verbesserte Schmerzwirkung im Vergleich zu CMM allein 1 SCS ist eine Alternative zur Reoperation bei Leg Pain 2 Es konnte kein effect bzgl. Back Pain gezeigt werden 1,2 HF10 therapie ist zur Therapie von Leg und Back Pain 4,5 HF10 therapie verbessert den Back Pain 3,4,5 HF10 therapie verursacht keine Parästhesien 3,4,5 Die Resporderrate war bei HF10 therapie höher als bei traditionellen SCS 4,5 Schmerzbesserung für zumindest 24 Monate 3,5 Ähnlich,jedoch keine klinische Verbesserung der Leg Pain wirkung im Vergleich zu traditionellen SCS 6 Geringe Paresthesieverbesserung im Vergleich zu traditionellen SCS 6 Es konnte keine Besserung bei Back Pain gezeigt werden 6 1. North, et al. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56(1):98-106 2. Kumar K, et al. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery. October 2008;63(4):762-770 3. Al-Kaisy, et al. Sustained Effectiveness of 10 khz High-Frequency Spinal Cord Stimulation for Patients with Chronic, Low Back Pain: 24-Month Results of a Prospective Multicenter Study. Pain Medicine. 2014; 15: 347-354 4. Kapural L., et al. Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain. Anesthesiology, 123(4) 5. Kapural L, et al. Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-month Results from a Multicenter, Randomized, Controlled Pivotal Trial. Neurosurgery. Published 09 2016 [Epub ahead of Print]. 6. Deer, T. Presented at NANS 2015, Las Vegas, NV. Late Breaking Data
Fazit HF 10 Therapie ist eine gute Methode zur Behandlung von Back und Leg Pain. Es entstehen keine störenden Parästhesien Die Implantation ist in Narkose möglich Durch RCT Studie hoher Evidenzgrad