(114 days)
Not Found
No
The description focuses on electrical stimulation and user control via a mobile app, with no mention of AI/ML algorithms for treatment personalization, prediction, or analysis.
Yes
The device is intended for the acute treatment of migraine with or without aura, and its description details how it delivers low-energy electrical pulses to the upper arm for therapeutic effect (pain relief and symptom reduction). The performance studies also assess its clinical efficacy in relieving migraine headache pain and associated symptoms.
No
The device is intended for the acute treatment of migraine, not for diagnosing it. It delivers electrical pulses to alleviate symptoms.
No
The device description explicitly states that the Nerivio is a "wearable, battery-powered device" with "device hardware" consisting of an armband containing electronic circuitry, a battery, and electrodes. While it is controlled by software, it is not solely software.
Based on the provided information, the Nerivio device is not an In Vitro Diagnostic (IVD).
Here's why:
- Intended Use: The intended use clearly states that the Nerivio is for the "acute treatment of migraine." This indicates a therapeutic purpose, not a diagnostic one.
- Device Description: The description details a wearable device that delivers electrical pulses to the upper arm for pain relief. This is a physical intervention, not a test performed on biological samples.
- Lack of IVD Characteristics: The description does not mention any of the typical characteristics of an IVD, such as:
- Analyzing biological samples (blood, urine, tissue, etc.)
- Detecting or measuring substances in biological samples
- Providing information for diagnosis, monitoring, or screening of diseases or conditions.
The Nerivio is a therapeutic device used to treat a medical condition, not a device used to diagnose or provide information about a medical condition based on in vitro testing.
N/A
Intended Use / Indications for Use
The Nerivio is intended for acute treatment of migraine with or without aura in patients 18 years of age or older. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura.
Product codes
QGT
Device Description
The Nerivio is a wearable, battery-powered device that is controlled by a mobile application. The system delivers low energy electrical pulses to the upper arm for 45 minutes per treatment, after which the device turns off automatically.
The device hardware consists of an armband intended to be worn on a user's upper arm. The armband contains the electronic circuitry and the battery in a plastic storage case as well as two electrodes that are attached to the interior of the armband and placed against the user's skin.
The device is operated and controlled via software that is installed and run on a user's personal mobile device such as a mobile phone or tablet. The device hardware communicates with the mobile application through a Bluetooth protocol. This mobile application software allows the user to control the stimulation intensity from 0 to 100% (representing intensity levels of 0- 40mA), to start or stop the stimulation program, and to view device status such as the device's connection state, a progress bar for stimulation duration, battery level, and user notifications.
The patient is instructed to adjust the intensity to the strongest stimulation level below the perceived pain level. Treatments with Nerivio are intended to be self-administered by the user immediately after the onset of migraine headache or aura.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Upper arm
Indicated Patient Age Range
18 years of age or older
Intended User / Care Setting
prescription use, self-administered device for use in the home environment
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Two clinical studies of the Nerivio device in chronic migraine patients were performed to assess the Nerivio safety and clinical efficacy in the chronic migraine population. Specifically, it assessed the capability of the Nerivio device to relieve migraine headache pain and associated migraine symptoms in patients with chronic migraine. All studies were in compliance with 21 CFR parts 50, 56, and 812
The first study was a prospective, open-label, single arm, multicenter study conducted at 2 sites. 42 patients were recruited in this study. Eligible participants were adults (18–75 years old) who met the International Classification of Headache Disorders (ICHD-3) criteria for chronic migraine (at least 15 headache days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine).
Participants treated their migraine attacks at home for 4 weeks (treatment phase), within one hour from migraine symptom onset. Participants were instructed to avoid taking rescue medications prior or within two hours post-treatment. Pain scores, absence/presence of associated migraine symptoms, and functional disability were recorded at baseline. 2- and 24-hours post-treatment using the electronic diary application installed on the participants' smartphones.
The primary efficacy endpoint was the proportion of participants who achieved pain relief at 2 hours post-treatment in the test treatment, defined as improvement from severe or moderate pain to mild or none, or, improvement from mild pain to none.
38 participants completed at least one treatment in response to a migraine. A total of 296 qualifying migraine headaches were treated with Nerivio. Pain relief and pain-free at 2 hours were achieved by 50.0% (19/38; Cl95% 33.4-66.6%) and 26.3% (10/38; Cl95% 13.4-43.1%) participants, respectively. Pain relief was sustained for 24 hours in 83.3% (10/12; C195% 51.6-97.9%) of the participants (7 participants did not report pain level at 24 hours and were thus excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 58.8% (10/17; Cl95% 32.9-81.6%)), 37.5% (9/24; Cl95% 18.8-59.4%), and 50.0% (8/16; Cl95% 24.7-75.3%) participants, respectively. Furthermore, 46.7% (14/30; Cl95% 28.3-65.7%) participants experienced improvement in functional ability at 2 hours and 72.7% (16/22; C/95% 49.8-89.3%) participants experienced improvement in functional ability at 24 hours (8 participants with missing data at 24 hours were excluded from the analysis). Consistency analyses across all attacks (excluding the training treatment) demonstrated that 73.7% (28/38) of the participants experienced pain relief in at least 50% of their treated attacks
The second study was also a prospective, open-label, single arm, multicenter study conducted at 9 sites in the USA. Eligible participants were adults (18–75 years old) who met the International Classification of Headache Disorders (ICHD-3) criteria for chronic migraine (at least 15 headache days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine).
Following a 4 weeks "Run-in" phase, eligible participants were asked to treat their migraine attacks at home for 4 weeks with their optimal stimulation intensity, as soon as possible after migraine headache began and always within one hour of attack onset. Participants were instructed to avoid taking rescue medications prior or within the first two hours post-treatment. Pain scores, absence/presence of migraine associated symptoms, and functional disability were recorded at baseline, 2- and 24-hours post-treatment using the electronic diary application.
The primary efficacy endpoint was the proportion of participants who achieved pain relief at 2 hours post-treatment in the test treatment, defined as improvement from severe or moderate pain to mild or none, or, improvement from mild pain to none.
97 participants completed at least one treatment of a qualifying migraine headache (the training treatment) and 91 participants completed the test treatment with evaluable data at baseline and at 2 hours, forming the final analysis set (5 participants did not have qualifying migraine headaches and 3 participants had missing data in the test treatment at baseline or at 2 hours).
A total of 493 evaluable treatments (excluding the training treatment) of qualifying migraine headaches were conducted by the 91 participants included in the analyses, with an average of 5.4±2.8 evaluable treatments per patient per 4 weeks.
The primary, secondary, and exploratory endpoints of a single attack were conducted on the test treatment of the final analysis set of 91 participants. Pain relief and pain-free at 2 hours were achieved by 59.3% (54/91; Clss% 48.5-69.5%) and 20.9% (19/91; Clss% 13.0-30.6%) of the participants, respectively. Pain relief was sustained for 24 hours in 71.1% (32/45; C195% 51.6-97.9%) of the participants (9 participants did not report pain level at 24 hours and were thus excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 48.8% (20/41; Cl9s% 32.8-64.8%), 40.5% (30/74; Clos% 29.2-52.5%), and 44.6% (29/65; Clg5% 32.2-57.4%) participants, respectively.
Furthermore, 59.4% (19/32; Clos% 40.6-76.3%) of the participants experienced improvement in functional ability at 2 hours (participants with missing data at baseline or at 2 hours were excluded from the analysis) and 50.0% (7/14: Clg5% 23.0-76.9%) of the participants experienced improvement in functional ability at 24 hours (participants with missing data at baseline or at 24 hours were excluded from the analysis).
Consistency analyses across all attacks (excluding the training treatment) demonstrated that 57.1% (52/91) of the participants experienced pain relief in at least 50% of their treated attacks.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 882.5899 Trunk and limb electrical stimulator to treat headache.
(a)
Identification. A trunk and limb electrical stimulator to treat headache is a device intended to treat headache through the application of electrical stimulation anywhere on the body of the patient apart from the patient's head or neck through electrodes placed on the skin. The stimulation may be provided transcutaneously or percutaneously.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. This testing must include:
(i) Characterization of the electrical stimulation, including the following: Waveforms; output modes; maximum output voltage and maximum output current (at 500Ω, 2kΩ, and 10kΩ loads); pulse duration; frequency; net charge per pulse; and maximum phase charge, maximum current density, maximum average current, and maximum average power density (at 500Ω);
(ii) Characterization of the impedance monitoring system; and
(iii) Characterization of the electrode performance including the electrical performance, adhesive integrity, shelf-life, reusability, and current distribution of the electrode surface area.
(2) The patient-contacting components of the device must be demonstrated to be biocompatible.
(3) Performance testing must demonstrate electromagnetic compatibility and electrical, mechanical, and thermal safety in the intended use environment.
(4) Software verification, validation, and hazard analysis must be performed.
(5) Labeling must include the following:
(i) Instructions for use, including the typical sensations experienced during treatment;
(ii) A detailed summary of the electrical stimulation output, and the device technical parameters, including any wireless specifications;
(iii) A shelf life for the electrodes and reuse information; and
(iv) Instructions on care and cleaning of the device.
0
Image /page/0/Picture/0 description: The image shows the logo for the U.S. Food and Drug Administration (FDA). The logo consists of two parts: on the left is the Department of Health and Human Services logo, and on the right is the FDA logo. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. Food & Drug Administration".
10/23/2020
Theranica Bio-Electronics LTD. % Janice Hogan Hogan Lovells US LLP 1735 Market Street, Floor 23 Philadelphia, Pennsylvania 19103
Re: K201824
Trade/Device Name: Nerivio Regulation Number: 21 CFR 882.5899 Regulation Name: Trunk and limb electrical stimulator to treat headache Regulatory Class: Class II Product Code: QGT Dated: September 28, 2020 Received: September 28, 2020
Dear Janice Hogan:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part
1
801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Xiaorui Tang -S
Xiaorui Tang Acting Assistant Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K201824
Device Name
Nerivio
Indications for Use (Describe)
The Nerivio is intended for acute treatment of migraine with or without aura in patients 18 years of age or older. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) SUMMARY
Theranica Bio-Electronics LTD.'s Nerivio
Submitter
Theranica Bio-Electronics LTD. 4 Ha-Omanut St. Netanya, ISRAEL, 4250438
Phone: +972-72-3909755
Facsimile: +972-72-3909762
Contact Person: Dagan Harris
Date Prepared: October 22, 2020
Name of Device: Nerivio
Common or Usual Name: Nerivio
Classification Name: Trunk and limb electrical stimulator to treat headache
Regulatory Class: Class II
Product Code: QGT
Predicate Device:
Device Name: Nerivio Migra Manufacturer: Theranica Bio-Electronics LTD. 510(K) Number: DEN180059
Device Description:
The Nerivio is a wearable, battery-powered device that is controlled by a mobile application. The system delivers low energy electrical pulses to the upper arm for 45 minutes per treatment, after which the device turns off automatically.
The device hardware consists of an armband intended to be worn on a user's upper arm. The armband contains the electronic circuitry and the battery in a plastic storage case as well as two electrodes that are attached to the interior of the armband and placed against the user's skin.
The device is operated and controlled via software that is installed and run on a user's personal mobile device such as a mobile phone or tablet. The device hardware communicates with the mobile application through a Bluetooth protocol. This mobile application software allows the user to control the stimulation intensity from 0 to 100% (representing intensity levels of 0- 40mA), to start or stop the stimulation program, and to view device status such as the device's connection state, a progress bar for stimulation duration, battery level, and user notifications.
The patient is instructed to adjust the intensity to the strongest stimulation level below the perceived pain level. Treatments with Nerivio are intended to be self-administered by the user immediately after the onset of migraine headache or aura.
4
Intended Use / Indications for Use
The Nerivio is intended for acute treatment of migraine with or without aura in patients 18 years of age or older. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura.
Summary of Technological Characteristics
Both the device and the predicate device function as remote electrical neuromodulation (REN) devices that utilize electro-stimulation that relieves migraine headache, using equivalent output parameters. The basic pulse structure is biphasic, with symmetrical interleaving phases and rectangular shape. The amplitude shift signal alternates between a nominal maximum and a nominal minimum of the amplitude signal. The maximal output current is 40mA. The assumed impedance is 1K ohm +/- 500 ohms.
| Characteristic | Subject Device | Predicate Device | Comparison |
|---|---|---|---|
| Submission Number | K201824 | DEN180059 | N/A |
| Device Name | Nerivio | Nerivio Migra | Minor modification |
| for marketing | |||
| Manufacturer | Theranica Bio- | ||
| Electronics LTD. | Theranica Bio- | ||
| Electronics LTD. | Same | ||
| Indications for Use | The Nerivio is intended | ||
| for acute treatment of | |||
| migraine with or without | |||
| aura in patients 18 | |||
| years of age or older. It | |||
| is a prescription use, | |||
| self-administered | |||
| device for use in the | |||
| home environment at | |||
| the onset of migraine | |||
| headache or aura. | The Nerivio Migra is | ||
| indicated for acute | |||
| treatment of migraine | |||
| with or without aura in | |||
| patients 18 years of age | |||
| or older who do not | |||
| have chronic migraine. | |||
| It is a prescription use, | |||
| self-administered | |||
| device for use in the | |||
| home environment at | |||
| the onset of migraine | |||
| headache or aura. | Modified to | ||
| remove limitation | |||
| for the treatment | |||
| of chronic | |||
| migraine | |||
| Prescription or OTC | Prescription | Prescription | Same |
| Electrical waveform | Biphasic rectangular, | ||
| modulated | Biphasic rectangular, | ||
| modulated | Same | ||
| Electrical output | |||
| Max output voltage | |||
| 500 Ω | |||
| 2 KΩ | |||
| 10 ΚΩ | 20V (measured) | ||
| 60V (measured) | |||
| 60V (measured) | 20V (measured) | ||
| 60V (measured) | |||
| 60V (measured) | Same | ||
| Max output current | |||
| 500 Ω | |||
| 2 KΩ | |||
| 10 KΩ | 40 mA | ||
| 30 mA | |||
| 6mA | 40 mA | ||
| 30 mA | |||
| 6mA | Same | ||
| Maximum phase charge | 8µC | 8µC | Same |
| Maximum average | |||
| current (500Ω) | 1.76mA | 1.76mA | Same |
| Maximum current | |||
| density (peak) (500Ω) | 1.6mA/cm2 | 1.6mA/cm2 | Same |
| Maximum current | |||
| density (r.m.s) (500Ω) | 0.34mA/cm | 0.34mA/cm | Same |
| Maximum average | |||
| current density (abs | |||
| value) (500Ω) | 0.07mA/cm2 | 0.07mA/cm2 | Same |
| Maximum average | |||
| power density (500Ω) | 1.41mW/cm2 | 1.41mW/cm2 | Same |
| Frequency | |||
| Primary phase duration | |||
| [µSec] | 200 | 200 | Same |
| Pulse Duration [µSec] | 400 | 400 | Same |
| Electrode Area | 25 cm2 | 25 cm2 | Same |
| Treatment location | Upper arm | Upper arm | Same |
| Treatment duration | 45 min. | 45 min. | Same |
| Reusable | Yes | Yes | Same |
| # of treatments per one | |||
| device | 12 treatments | 8 treatments | Allows for more |
| treatments prior to | |||
| replacement. | |||
| Does not raise | |||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Power source | LiMnO2 cell battery | Lithium-Ion battery | Does not raise |
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| On/off button | Power push-button | ON/OFF switch | Does not raise |
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Dimensions | Device - 12.0 x 7.5 x 1.5 | ||
| cm | |||
| Armband - 48.0 x 10.0 | |||
| x 0.3 cm | Device+Armband = | ||
| 49.0 X 11.0 X 3.0 cm | Does not raise | ||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Weight | Device - 50 gr | ||
| Armband - 33 gr | 125 gr (device + | ||
| armband) | Does not raise | ||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Shelf life | 24 months | 9 months | Does not raise |
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Mobile Application | Yes | Yes | Same function for |
| Different GUI. | |||
| Does not raise | |||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Biocompatibility | Yes. | Yes | Different armband |
| coating material. | |||
| Does not raise | |||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Sterile | No | No | Same |
| Processor control | Yes. | Yes | Same |
| Wireless control | Yes. | Yes | Same |
| Automatic | |||
| overload trip | Yes. | Yes | Same |
| Automatic no | |||
| load trip | Yes. | Yes | Same |
| Automatic shut | |||
| off | Yes. | Yes | Same |
| Stimulation | |||
| intensity control | Yes. | Yes | Same |
5
6
Table 1 provides a comparison between the key functional features of the Nerivio and predicate device.
| Characteristic | Subject Device | Predicate Device | Comparison |
|---|---|---|---|
| Submission Number | K201824 | DEN180059 | N/A |
| Device Name | Nerivio | Nerivio Migra | Minor modification |
| for marketing | |||
| Manufacturer | Theranica Bio- | ||
| Electronics LTD. | Theranica Bio- | ||
| Electronics LTD. | Same | ||
| Indications for Use | The Nerivio is intended | ||
| for acute treatment of | |||
| migraine with or without | |||
| aura in patients 18 | |||
| years of age or older. It | |||
| is a prescription use, | |||
| self-administered | |||
| device for use in the | |||
| home environment at | |||
| the onset of migraine | |||
| headache or aura. | The Nerivio Migra is | ||
| indicated for acute | |||
| treatment of migraine | |||
| with or without aura in | |||
| patients 18 years of age | |||
| or older who do not | |||
| have chronic migraine. | |||
| It is a prescription use, | |||
| self-administered | |||
| device for use in the | |||
| home environment at | |||
| the onset of migraine | |||
| headache or aura. | Modified to | ||
| remove limitation | |||
| for the treatment | |||
| of chronic | |||
| migraine | |||
| Prescription or OTC | Prescription | Prescription | Same |
| Electrical waveform | Biphasic rectangular, | ||
| modulated | Biphasic rectangular, | ||
| modulated | Same | ||
| Electrical output | |||
| Max output voltage | Same | ||
| 500 Ω | 20V (measured) | 20V (measured) | |
| 2 KΩ | 60V (measured) | 60V (measured) | |
| 10 KΩ | 60V (measured) | 60V (measured) | |
| Max output current | Same | ||
| 500 Ω | 40 mA | 40 mA | |
| 2 KΩ | 30 mA | 30 mA | |
| 10 KΩ | 6mA | 6mA | |
| Maximum phase charge | 8µC | 8µC | Same |
| (500Ω) | |||
| Maximum average | |||
| current (500Ω) | 1.76mA | 1.76mA | Same |
| Maximum current | |||
| density (peak) (500Ω) | 1.6mA/cm2 | 1.6mA/cm2 | Same |
| Maximum current | |||
| density (r.m.s) (500Ω) | 0.34mA/cm | 0.34mA/cm | Same |
| Maximum average | |||
| current density (abs | |||
| value) (500Ω) | 0.07mA/cm2 | 0.07mA/cm2 | Same |
| Maximum average | |||
| power density (500Ω) | 1.41mW/cm2 | 1.41mW/cm2 | Same |
| Frequency | |||
| Primary phase duration | |||
| [µSec] | 200 | 200 | Same |
| Pulse Duration [µSec] | 400 | 400 | Same |
| Electrode Area | 25 cm² | 25 cm² | Same |
| Treatment location | Upper arm | Upper arm | Same |
| Treatment duration | 45 min. | 45 min. | Same |
| Reusable | Yes | Yes | Same |
| # of treatments per one | |||
| device | 12 treatments | 8 treatments | Allows for more |
| treatments prior to | |||
| replacement. | |||
| Does not raise | |||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Power source | LiMnO2 cell battery | Lithium-Ion battery | Does not raise |
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| On/off button | Power push-button | ON/OFF switch | Does not raise |
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Dimensions | Device – 12.0 x 7.5 x 1.5 | ||
| cm | |||
| Armband - 48.0 x 10.0 | |||
| x 0.3 cm | Device+Armband = | ||
| 49.0 X 11.0 X 3.0 cm | Does not raise | ||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Weight | Device - 50 gr | ||
| Armband - 33 gr | 125 gr (device + | ||
| armband) | Does not raise | ||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Shelf life | 24 months | 9 months | Does not raise |
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Mobile Application | |||
| software | Yes | Yes | Same function for |
| treatment control. | |||
| Different GUI. | |||
| Does not raise | |||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Biocompatibility | Yes. | Yes | Different armband |
| coating material. | |||
| Does not raise | |||
| different questions | |||
| of safety and | |||
| effectiveness. | |||
| Sterile | No | No | Same |
| Processor control | Yes. | Yes | Same |
| Wireless control | Yes. | Yes | Same |
| Automatic | |||
| overload trip | Yes. | Yes | Same |
| Automatic no | |||
| load trip | Yes. | Yes | Same |
| Automatic shut | |||
| off | Yes. | Yes | Same |
| Stimulation | |||
| intensity control | Yes. | Yes | Same |
7
8
Table 1 – Comparison between subject and predicate devices
Performance Data
Non-Clinical Tests:
Nerivio non-clinical bench tests addressed verification and validation of the hardware and software. Device performance testing is summarized in Table 2.
9
| Test | Test description | |
|---|---|---|
| Safety tests | According to ANSI AAMI ES60601-1, IEC 60601-1-11 and IEC60601-2-10 | |
| EMC and radio tests | According to EN IEC 60601-1-2 | |
| Wireless coexistence | According to ANSI C63.27 | |
| FCC | According to 47CFR | |
| part 15.347 | ||
| part 15.205 | ||
| part 15.207 part 15.209 | ||
| Biocompatibility | According to ISO 10993 |
Table 2 – Nerivio non-clinical tests list
In addition, the company conducted internal bench tests to verify and validate the device battery's lifetime and safety, firmware testing, system testing, mobile application software testing and usability testing. In all instances, the Nerivio functioned as intended and expected.
Clinical Tests:
Two clinical studies of the Nerivio device in chronic migraine patients were performed to assess the Nerivio safety and clinical efficacy in the chronic migraine population. Specifically, it assessed the capability of the Nerivio device to relieve migraine headache pain and associated migraine symptoms in patients with chronic migraine. All studies were in compliance with 21 CFR parts 50, 56, and 812
The first study was a prospective, open-label, single arm, multicenter study conducted at 2 sites. 42 patients were recruited in this study. Eligible participants were adults (18–75 years old) who met the International Classification of Headache Disorders (ICHD-3) criteria for chronic migraine (at least 15 headache days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine).
Participants treated their migraine attacks at home for 4 weeks (treatment phase), within one hour from migraine symptom onset. Participants were instructed to avoid taking rescue medications prior or within two hours post-treatment. Pain scores, absence/presence of associated migraine symptoms, and functional disability were recorded at baseline. 2- and 24-hours post-treatment using the electronic diary application installed on the participants' smartphones.
The primary efficacy endpoint was the proportion of participants who achieved pain relief at 2 hours post-treatment in the test treatment, defined as improvement from severe or moderate pain to mild or none, or, improvement from mild pain to none.
38 participants completed at least one treatment in response to a migraine. A total of 296 qualifying migraine headaches were treated with Nerivio. Pain relief and pain-free at 2 hours were achieved by 50.0% (19/38; Cl95% 33.4-66.6%) and 26.3% (10/38; Cl95% 13.4-43.1%) participants, respectively. Pain relief was sustained for 24 hours in 83.3% (10/12; C195% 51.6-97.9%) of the participants (7 participants did not report pain level at 24 hours and were thus excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 58.8% (10/17; Cl95% 32.9-81.6%)), 37.5% (9/24; Cl95% 18.8-59.4%), and 50.0% (8/16; Cl95% 24.7-75.3%) participants, respectively. Furthermore, 46.7% (14/30; Cl95% 28.3-65.7%) participants experienced improvement in functional
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ability at 2 hours and 72.7% (16/22; C/95% 49.8-89.3%) participants experienced improvement in functional ability at 24 hours (8 participants with missing data at 24 hours were excluded from the analysis). Consistency analyses across all attacks (excluding the training treatment) demonstrated that 73.7% (28/38) of the participants experienced pain relief in at least 50% of their treated attacks
One device-related adverse event was reported (1.8% of patients [1/42] or 0.003% of treatments [1/296]). This adverse event included bilateral tingling in the temples, disturbed and double vision. The event resolved within 48 hours following drug therapy. There were no device-related serious adverse events and none of the participants withdrew from the study due to device-related adverse events.
The second study was also a prospective, open-label, single arm, multicenter study conducted at 9 sites in the USA. Eligible participants were adults (18–75 years old) who met the International Classification of Headache Disorders (ICHD-3) criteria for chronic migraine (at least 15 headache days a month, with at least eight days a month on which their headaches and associated symptoms meet diagnostic criteria for migraine).
Following a 4 weeks "Run-in" phase, eligible participants were asked to treat their migraine attacks at home for 4 weeks with their optimal stimulation intensity, as soon as possible after migraine headache began and always within one hour of attack onset. Participants were instructed to avoid taking rescue medications prior or within the first two hours post-treatment. Pain scores, absence/presence of migraine associated symptoms, and functional disability were recorded at baseline, 2- and 24-hours post-treatment using the electronic diary application.
The primary efficacy endpoint was the proportion of participants who achieved pain relief at 2 hours post-treatment in the test treatment, defined as improvement from severe or moderate pain to mild or none, or, improvement from mild pain to none.
97 participants completed at least one treatment of a qualifying migraine headache (the training treatment) and 91 participants completed the test treatment with evaluable data at baseline and at 2 hours, forming the final analysis set (5 participants did not have qualifying migraine headaches and 3 participants had missing data in the test treatment at baseline or at 2 hours).
A total of 493 evaluable treatments (excluding the training treatment) of qualifying migraine headaches were conducted by the 91 participants included in the analyses, with an average of 5.4±2.8 evaluable treatments per patient per 4 weeks.
The primary, secondary, and exploratory endpoints of a single attack were conducted on the test treatment of the final analysis set of 91 participants. Pain relief and pain-free at 2 hours were achieved by 59.3% (54/91; Clss% 48.5-69.5%) and 20.9% (19/91; Clss% 13.0-30.6%) of the participants, respectively. Pain relief was sustained for 24 hours in 71.1% (32/45; C195% 51.6-97.9%) of the participants (9 participants did not report pain level at 24 hours and were thus excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 48.8% (20/41; Cl9s% 32.8-64.8%), 40.5% (30/74; Clos% 29.2-52.5%), and 44.6% (29/65; Clg5% 32.2-57.4%) participants, respectively.
Furthermore, 59.4% (19/32; Clos% 40.6-76.3%) of the participants experienced improvement in functional ability at 2 hours (participants with missing data at baseline or at 2 hours were excluded
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from the analysis) and 50.0% (7/14: Clg5% 23.0-76.9%) of the participants experienced improvement in functional ability at 24 hours (participants with missing data at baseline or at 24 hours were excluded from the analysis).
Consistency analyses across all attacks (excluding the training treatment) demonstrated that 57.1% (52/91) of the participants experienced pain relief in at least 50% of their treated attacks.
One device-related adverse event was reported (1.0% (1/99) in which pain in the arm was felt following the use of the device on that arm. The device-related adverse event was mild, resolved within 24 hours without medication.
Based on the clinical performance that was documented in these studies, the Nerivio has a safety and effectiveness profile that is similar to the predicate device.
Conclusions
The Nerivio has the same intended use and similar indications (with the modification to remove the limitation for the treatment of chronic migraine patients), technological characteristics, and principles of operation as its predicate device. The minor differences in the indications do not alter the intended therapeutic use of the device and do not affect its safety and effectiveness when used as labeled. In addition, the minor technological differences between the Nerivio and its predicate devices raise no different questions of safety, efficacy, or usability. Performance data demonstrate that the Nerivio is as safe and effective as the Nerivio Migra. Thus, the Nerivio is substantially equivalent to its predicate.