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Trial registered on ANZCTR


Registration number
ACTRN12615000713594
Ethics application status
Approved
Date submitted
25/06/2015
Date registered
9/07/2015
Date last updated
7/01/2020
Date data sharing statement initially provided
30/08/2019
Date results information initially provided
30/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and performance of Saluda Medical's EvokeTM with feedback control in patients with chronic pain to treat their upper or lower limb pain
Scientific title
A prospective study evaluating the safety and performance of Saluda Medical’s EvokeTM Spinal Cord Stimulation System incorporating feedback control to treat patients with chronic pain of the trunk and limbs
Secondary ID [1] 286965 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic upper and lower limb pain 295426 0
Condition category
Condition code
Anaesthesiology 295680 295680 0 0
Pain management
Neurological 295769 295769 0 0
Other neurological disorders
Surgery 295770 295770 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a prospective study examining the safety and performance of using neural stimulation incorporating feedback to treat patients with chronic pain. Patients will be diagnosed with chronic pain. All patients will be candidates for stimulation and be scheduled to undergo implantation of a trial lead followed by a trial evaluation. Up to 110 patients will be enrolled (trialled). The assessment of performance against the criterion will be performed at visit 1 (1 month post implant), safety will be assessed by analysis of AEs throughout the study period. The performance criterion defined by the sponsor is based upon successful delivery of neuromodulation in feedback mode in 80% of implanted patients (i.e. patients who have successfully passed the trial phase and proceed to surgery for the fully implanted system).
After eligible patients have signed informed consent and baseline data will be collected. They will be enrolled in the study when they undergo implantation of trial stimulation leads. This procedure, performed by pain specialist, will be followed by a trial of stimulation (7- 10 days period) using the EvokeTM External Closed Loop Stimulator (eCLS). During this period various parameters will be tested and ECAPSs will be recorded. Feedback will be assessed and may be used. Patients who have had a successful trial, success is determined by a 40% reduction in pain using the visual analogue scale, will then be implanted with the EvokeTM Closed Loop Stimulator (CLS).
Patients will return to the clinic for evaluations 1 month + 7 days, 3 months + 14 days, 6 months + 14 days, 12 months + 21 days, 15 months + 28 days, 18 months + 28 days, 21 months + 28 days, and 24 months + 28 days post implantation. Evaluations will include measures of pain, functional disability, quality of life, patient satisfaction and paresthesia characteristics. All adverse events will be recorded. Patients may be asked to have their evaluations videotaped. This will involve the patient signing an additional consent.
At the end of the study, patient may be able to continue Spinal Cord Stimulation with his implanted device if it is found to be of benefit to him in treating his pain. This decision will be made in consultation between patient and his treating doctor.
Intervention code [1] 292172 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295383 0
Programmability in feedback controlled stimulation mode is defined as the systems ability to automatically adjust stimulation output to maintain a desired ECAP setting determined by the FCE/coordinator or clinician with the subject.
Timepoint [1] 295383 0
Data will be collected at the trial assessment and following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [1] 315479 0
All reported adverse events.
The adverse event can be any change, undesired, noxious or
pathological in a patient or participant illustrated by signs, symptoms
and /or laboratory changes that occur during a clinical trial, whether or
not considered drug/treatment related.
If adverse experiences occur, the first concern will be the safety of the
patient. Appropriate medical intervention will be made. Any device
related adverse experiences or complications observed by the
investigator or reported by the patients will be recorded in the
appropriate section of the patient's case report forms in accordance with NSW Health GL2010_014
Timepoint [1] 315479 0
Clinic Visit (from day 1 to 24 month post-implant)
Secondary outcome [2] 315480 0
Brief pain inventory: pain relief, pain quality and patient perception of pain collected using 0 to 10 numeric scale.
Timepoint [2] 315480 0
Data will be collected at the baseline, trial assessment and following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [3] 315481 0
Oswestry Disability Index: The Oswestry Disability Index contains topics concerning intensity of pain, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel. Each topic category is followed by 6 statements describing different potential scenarios in the subject's life relating to the topic. The subject then checks the statement which most closely resembles their situation. Each question is scored on a scale of 0-5 with the first statement being zero and indicating the least amount of disability and the last statement being 5 indicating most severe disability. The final score ranges from 0 to 100, where 0 is equated with no disability and 100 corresponds to maximum disability.
Timepoint [3] 315481 0
Data will be collected at the baseline and following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [4] 315483 0
Pittsburgh Sleep Quality Index (PSQI): is a self-rated questionnaire, which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score.
Timepoint [4] 315483 0
Data will be collected at the baseline and following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [5] 315485 0
Visual Analogue scale: is a measure of pain. patient will be asked to
score his pain on a 10-cm line from no pain to worst pain by drawing a mark on the line.
Timepoint [5] 315485 0
Data will be collected at the baseline, trial assessment and following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [6] 315486 0
EQ-5D: The EQ-5D questionnaire captures health-related quality of life data in five key areas.
Timepoint [6] 315486 0
Data will be collected at the baseline and following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [7] 315487 0
Comparison of pain and paresthesia maps.
Data on the area of pain and paresthesia coverage will be collected by asking patient to highlight the areas on body map drawing.
The comparison between these two maps show the percentage of pain coverage by paresthesia and any changes on the followup visits.
Timepoint [7] 315487 0
Data will be collected at the baseline and following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [8] 315488 0
Neural response to changes in stimulation frequency, amplitude, pulse
width, pulse shape, pulse sequence and electrode configuration. The
Patient threshold, comfort and maximum level of stimulation as well as
parethesia sensation and pain coverage will be collected in a form for
each experiment for further research.
Timepoint [8] 315488 0
these experiments can be done in any of the follow-up visits or during the one week trialing the external device. Follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [9] 315489 0
posture changes: Subject will be asked to do some postural changes and report the stimulation strength and location of the stimulation.
Timepoint [9] 315489 0
Data will be collected following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.
Secondary outcome [10] 315490 0
Paresthesia Quality: The subject will be asked to rate from 0 to 4 the relevance of a series of words in regards to their feeling of the paresthesia.
Timepoint [10] 315490 0
Data will be collected following the permanent implant on follow-up visits. follow-up visits will be after one, three, six, twelve, fifteen, eighteen, twenty one and twenty four months after permanent implant.

Eligibility
Key inclusion criteria
Patients selected for this study must meet the following inclusion criteria:
1. Have been diagnosed with chronic, intractable pain (VAS = 6 for the past week), which has been refractory to conservative therapy for a minimum of 3 months.
2. Have been approved to undergo a trial of neural stimulation. Neural stimulation can include cervical or thoracic spinal cord stimulation.
3. Be an appropriate candidate for the surgical procedures required in this study based on the clinical judgment of the implanting physician
4. Be on a stable dose (no new, discontinued, or changes in dose) of all prescribed pain medication for at least 4 weeks prior to the trial
5. Be 18 years of age or older at the time of enrolment
6. Be willing and capable of giving written informed consent
7. Be willing and able to comply with study-related requirements, procedures, and visits.
8. Females of childbearing age must have a negative urine pregnancy test at baseline
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients selected for this study must not meet the following exclusion criteria:
1. Have a medical condition or pain in area(s) that could interfere with study procedures, accurate pain reporting, and/or confound evaluation of study endpoints, as determined by the Investigator
2. Have evidence of an active disruptive psychological or psychiatric disorder or other known condition significant enough to impact perception of pain, compliance with of intervention and/or ability to evaluate treatment outcomes
3. Are not a surgical candidate due to a diagnosis of an uncontrolled coagulation disorder, bleeding diathesis, progressive peripheral vascular disease or uncontrolled diabetes mellitus
4. Have an implanted pacemaker and/or another SCS system that may interfere with the Saluda system.
5. Have a condition currently requiring or likely to require the use of MRI or diathermy
6. Have a life expectancy of less than 1 year
7. Have an active systemic or local infection
8. Be allergic, or have shown hypersensitivity, to any materials of the neurostimulation system which come in contact with the body
9. Be pregnant or nursing (if female and sexually active, participant must be using a reliable form of birth control, be surgically sterile or be at least 2 years post-menopausal)
10. Have within 6 months of enrolment a significant untreated addiction to dependency-producing medications or have been a substance abuser (including alcohol and/or illicit drugs)
11. Be concomitantly participating in another clinical study
12. Be involved in an injury claim under current litigation

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Each patient complying with the inclusion/exclusion criteria, who is willing to participate in the study, and signs the informed consent, and have a trial procedure will be enrolled. Once enrolled, patient names will be entered into a patient enrolment log and given a patient number for the duration of the study. All patients will receive the same treatment and there will be no masking required.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nil
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The performance criterion defined by the sponsor is based upon successful delivery of neuromodulation in feedback mode in 80% of implanted patients (i.e. patients who have successfully passed the trial phase and proceed to surgery for the fully implanted system).

In order to demonstrate statistically that this threshold is achieved in this study, a non-inferiority test will be conducted utilizing a non-inferiority margin of 10%. Therefore, the following hypothesis statements will be employed:

H0: P= 0.80-d
H1: P>0.8- d; where d=0.10

It is anticipated that the true success rate associated with feedback capture is at least 90%. In order to have 85% power to determine that an observed rate of 90% can be considered non-inferior to the target of 80%, with a d=10%, a minimum of 28 subjects are required. This calculation assumes a 1-sided significance level of 0.05 and is based on an exact testing methodology.

This statistical test will be conducted on data from visit 1 (1-month post implantation of the permanent system), no assumptions will be made for missing data but we will include a conservative 15% attrition rate to ensure enough data samples are captured. As such up to 32 subjects who receive the fully implanted system will be required.

Secondary Endpoints and Baseline Measures
The subject demographics, diagnosis and previous treatments will be tabulated and descriptive statistics will be estimated. These include means (or medians) and standard deviations (or inter-quartile ranges) for continuous or ordinal variables and proportions for categorical variables. Questionnaire instruments will be analysed consistent with their validated methodology but at a minimum will include complete summary statistics and 95% confidence intervals.
Exploratory subgroup analyses will be conducted to determine if there exist relationships suggestive of enhanced effectiveness. Such findings will be used to generate hypotheses for future studies In addition, a number of multivariate techniques may be employed to address the impact of baseline covariates on score over time including repeated measures analysis and general estimating equations (GEE).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3964 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 3966 0
Lingard Private Hospital - Merewether
Recruitment hospital [3] 4369 0
Hamilton Day Surgery Centre - Hamilton South
Recruitment hospital [4] 5955 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [5] 5956 0
Glenferrie Private Hospital - Hawthorn

Funding & Sponsors
Funding source category [1] 291527 0
Commercial sector/Industry
Name [1] 291527 0
Saluda Medical Pty Ltd
Address [1] 291527 0
Saluda Medical Pty Ltd
Level1
407 Pacific Highway Artarmon NSW 2064
Country [1] 291527 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Saluda Medical Pty Ltd
Address
Saluda Medical Pty Ltd
Level1
407 Pacific Highway Artarmon NSW 2064
Country
Australia
Secondary sponsor category [1] 290208 0
None
Name [1] 290208 0
Address [1] 290208 0
Country [1] 290208 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293068 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 293068 0
Level 13
Kolling Building
Royal North Shore Hospital
St Leonard 2065 NSW
Ethics committee country [1] 293068 0
Australia
Date submitted for ethics approval [1] 293068 0
Approval date [1] 293068 0
22/06/2015
Ethics approval number [1] 293068 0
HREC/15/HAWKE/101
Ethics committee name [2] 295228 0
Bellberry Human research ethics committee
Ethics committee address [2] 295228 0
129 Glen Osmond rd Eastwood SA 5063
Ethics committee country [2] 295228 0
Australia
Date submitted for ethics approval [2] 295228 0
12/08/2015
Approval date [2] 295228 0
12/10/2015
Ethics approval number [2] 295228 0
2015-08-563
Ethics committee name [3] 295229 0
Macquarie University Human Research Etchics Committee
Ethics committee address [3] 295229 0
Research Office
Research Hub, Building C5C East
Macquarie University
NSW 2109
Ethics committee country [3] 295229 0
Australia
Date submitted for ethics approval [3] 295229 0
17/11/2015
Approval date [3] 295229 0
02/03/2016
Ethics approval number [3] 295229 0
5201500950

Summary
Brief summary
The primary objective of this study is demonstrating the performance and safety of EvokeTM spinal cord stimulation with feedback control on neural stimulation in patients with chronic pain with regard to pain relief and stimulation side effects.
A new technique has been developed to measure Evoked Compound
Action Potentials (ECAPs) or neural responses to neural stimulation, on the
same lead that delivers the stimulation.
This research will help advance neurostimulation technology.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58326 0
Prof Michael Cousins
Address 58326 0
Pain Management and Research Institute Douglas Building Royal North
Shore Hospital St Leonard NSW 2065
Country 58326 0
Australia
Phone 58326 0
+61 2 94631638
Fax 58326 0
Email 58326 0
Michael.Cousins@health.nsw.gov.au
Contact person for public queries
Name 58327 0
Ms Linda Critchley
Address 58327 0
Pain Management & Research Institute Royal North Shore Hospital St
Leonards NSW 2065
Country 58327 0
Australia
Phone 58327 0
+61 2 94631533
Fax 58327 0
Email 58327 0
Linda.Critchley@health.nsw.gov.au
Contact person for scientific queries
Name 58328 0
Dr Nastaran Hesam Shariati
Address 58328 0
Saluda Medical Level 1 407 Pacific Highway Artarmon NSW 2064
Country 58328 0
Australia
Phone 58328 0
+61 2 84058707
Fax 58328 0
Email 58328 0
nastaran.shariati@saludamedical.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 4448 0
1/Jul/2017
Marc Russo, Michael J. Cousins , …, Nastaran Hesam Shariati, John Parker. Effective Relief of Pain and Associated Symptoms with Closed-Loop Spinal Cord Stimulation System: Preliminary Results of the Avalon Study. Neuromodulation: Technology at the Neural Interface. July 2017. http://onlinelibrary.wiley.com/doi/10.1111/ner.12684/full
Attachments [1] 4448 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary