results of the burst trial
TRANSCRIPT
Results of the Burst Trial: A Prospective, Randomized, Controlled Trial
Assessing Burst Stimulation for the Treatment of Chronic Pain
Timothy R. Deer, MD
Peter S. Staats, MD
Representing the Burst investigators
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Disclosures• Timothy Deer is a consultant for Axonics, Bioness, St Jude Medical,
Saluda, Medtronic, Nevro, Nuvectra, Flowonix, Vertos, and Jazz – Minority Stock options: Axonics, Bioness, Nevro, Vertos, Saluda
– Previous stock options: Spinal Modulation
– Funded research by St Jude Medical, Nevro, Jazz, and Saluda
• Peter Staats is a consultant for St Jude, Medtronic Nevro, Boston Scientific – Board of Director and minority ownership: ElectroCore Medical
– Research funded by Medtronic, St Jude Medical, Boston Scientific, Saluda, Grunenthal, Nevro, and Bioness
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Caution: The Burst waveform is investigational and not available in the U.S.
Burst Investigators and Steering Committee
Principal Investigators
Kasra Amirdelfan, MD
Allen Burton, MD
Vu Dang, MD
Bart Edmiston, MD
Alain Fabi, MD
Steven Falowski, MD
Timothy Houden, MD
Rafael Justiz, MD
Christopher Kim, MD
Camden Kneeland, MD
Carroll Mcleod, MD
Gregory Phillips, MD
Julie Pilitsis, MD
Phillip Smith, DO
Alexander Taghva, MD
Edward Tavel, MD
Jacob Vella, MD
Derron Wilson, MD
Thomas Yearwood, MD
Steering Committee:
Timothy Deer, MD
Richard North, MD
Konstantin Slavin, MD
Peter Staats, MD
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Background
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Current Neuromodulation Dynamics
• Increasing stigma and negative outcomes from long-term opioid use in chronic pain
– Diversion
– Abuse
– Overdose
• Growing evidence for improved outcomes and healthcare economics with earlier intervention
– Kumar’s last work
– NACC
• Significant opportunities for growth of Patient access:– SCS innovation– Novel stimulation modes and new anatomical targets provide
differentiation from our previous therapies
Burst Stimulation Mimics Natural Neuronal Signaling
• Burst firing is a naturally occurring signaling modality in human physiology and is interpreted differently by the nervous system1,2,3.
• Thalamic cells can fire in tonic and burst modes1.
• Thalamic burst firing considered a more potent activator of the cortex2,3
.
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1. Jahnsen H, Llinás R. : Voltage-dependent Burst-to-tonic switching of thalamic cell activity: an in vitro study. Arch Ital Biol. 1984 Mar;122(1):73-82.
2. Harvey A. Swadlow1 & Alexander G. Gusev : The impact of 'Bursting' thalamic impulses at a neocortical synapse. Nature Neuroscience 4, 402 - 408 (2001).
3. Sherman SM : A wake-up call from the thalamus. Nature neuroscience, 2001
Current Hypothesis: Burst stimulation may exert its main effect through an ability to modulate both lateral & medial pathways4
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Burst Stimulation
4. De Ridder D, et al. World Neurosurgery 2013.
Lateral Pathway Medial Pathway
(Ongoing Burst sub-study using PET and EEG to identify pathways during stimulation)
Artistic representation of the neuron/synapse
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Burst Trial Design
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Objectives• Demonstrate the safety and effectiveness of a
neurostimulation system that delivers both Burst and tonic stimulation
• Demonstrate non-inferiority of overall pain with Burst versus tonic stimulation
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Trial Design
• Multi-center, prospective
• Randomized (1:1)
• Crossover design (each subject was their own control)
• 76 subjects required to perform primary endpoint analysis
• Each patient had a device that could deliver both tonic and Burst stimulation
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Burst(12 weeks)
Tonic (12 weeks)
Tonic (12 weeks)
Burst(12 weeks)
Randomization
Key Exclusion Criteria:
• More than mild depression symptoms (BDI>24)
• History of substance abuse
Key Inclusion Criteria:
• Successful SCS tonic trial (>50% pain relief) system evaluation
• Chronic, intractable pain of trunk and/or limb
• Average 7-day VAS of 60 mm or higher prior to SCS tonic trial
• Stable pain medications
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Inclusion/Exclusion
Endpoints
Secondary Endpoint
• Superiority of Overall VAS
• Superiority of Trunk VAS
• Superiority of Limb VAS
• Paresthesia coverage
• Preference15
Primary Endpoint:
• Non-inferiority of Burst: Difference in overall VAS (mm) between Burst and Tonic (within subject controls)
Consented (N=173)
Completed Tonic Evaluation (N = 121)
Randomized (N = 100)
Burst / Tonic (N = 55)
Tonic / Burst (N = 45)
Completed 24 Week Visit
(N = 85)
52 Did not meet Inclusion/Exclusion
9 Failed Tonic Trial12 Exited for Other Reasons
Consort
Subjects• Age 59.1 (± 13.5) years• 12.8 (± 10.9) years of pain• 60% Female• Conditions:
– 42% FBSS– 37% Radiculopathies
• Overall baseline VAS = 75.1 mm • Mental Health:
– Mean BDI 10.1.(±6.0) with 75% having no depression– Not clinically meaningful catastrophizing
Mean PCS 20.2 (±11.8)
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Results
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InferiorNon-inferioritySuperiority
Primary Endpoint: Pain Intensity
-10 -8 -6 -4 -2 0 2 4 6 8
Mean Difference of Burst VAS - Tonic VAS (mm)
Overall VAS p = 0.035; Superiority
Trunk VAS p = 0.024; Superiority
Limb VAS p = 0.044; Superiority
Preferred Therapy Type:Percentage of Patients
A significantly higher proportion of patients preferred Burst (p<0.001).
69.4%
21.2%
9.4%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Burst (n=59) Tonic (n=18) No Preference (n=8)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Eliminated or reduced No reduction
SUNBurst™ Secondary Endpoint 100% of subjects reported
paresthesia during tonic stimulation
91% of subjects reported a decrease in paresthesia during Burst relative to
tonic
65% of subjects had no paresthesia while using
Burst9%
91%
65%Eliminated
26%Reduced
Paresthesia Reduction:Burst Compared With Tonic
Reasons for Preference
1.4%
10.3%
1.4%
10.3%
3.8%
1.5%
37.5%
33.7%
0% 5% 10% 15% 20% 25% 30% 35% 40%
Other
Preferred Paresthesia
Lack of Paresthesia
Better Pain Relief
Percentage of Patients
Preferred Burst (n=59) Preferred Tonic (n=18)
Adverse Events
• No unanticipated adverse events were reported
• Similar adverse event profile to other SCS studies
• Rates similar for both stimulation modes
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Adverse Events
Description Number of events
% Subjects
Unanticipated 0 0%
Serious Events Related to the Device or Procedures
2 1.1%
Procedure-Related 4 2.3%
Device- or Stimulation-Related 27 16.2%
Key Takeaways• Burst Stimulation provided superior pain relief vs. tonic for overall,
trunk, and limb pain
• Burst stimulation was preferred by the majority of patients (69%)
• Burst stimulation eliminated or reduced paresthesia in 91% of subjects
• There are patients who prefer paresthesia
• Each patient experienced both stimulation modes (tonic and Burst) and chose their preferred mode
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Thank you
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