(113 days)
-
The Trevo Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA). Endovascular therapy with the device should start within 6 hours of symptom onset.
-
The Trevo Retriever is intended to restore blood flow in the neurovasculature by removing thrombus in patients experiencing ischemic stroke within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.
-
The Trevo Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 segments with smaller core infarcts (0-50 cc for age < 80 years, 0-20 cc for age ≥ 80 years). Endovascular therapy with the device should start within 6-24 hours of time last seen well in patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy.
The Trevo Retriever family, including the Trevo ProVue and Trevo XP ProVue Retriever consists of a flexible, tapered core wire with a shaped section at the distal end. Platinum markers at the distal end allow fluoroscopic visualization. In addition, the shaped section is also radiopaque. Retriever dimensions are indicated on product label. The Retriever has a hydrophilic coating to reduce friction during use. The Retriever has a shaft marker to indicate proximity of Retriever tip relative to Microcatheter tip. A torque device is provided with the Retriever to facilitate manipulation. The torque device is used to lock the core wire to the microcatheter during the procedure. Locking of the torque device to the wire allows the microcatheter and Retriever to be retracted as a system during clot retrieval. An insertion tool is provided to introduce the Retriever into a Microcatheter. The Insertion Tool is a sheath in which the Retriever comes preloaded. Once half the retriever's length is inserted into the microcatheter, the insertion tool is removed. Retrievers have a modified proximal end that permits attachment of the Abbott Vascular DOC Guide Wire Extension (REF 22260). Joining Guide Wire Extension to Retriever facilitates removal or exchange of a catheter while maintaining Retriever position in anatomy. After exchange has been completed, the extension can be detached.
Here's a breakdown of the acceptance criteria and study information for the Trevo Retriever, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a bulleted or numbered list with specific thresholds. Instead, the study aims to demonstrate superior clinical outcomes for the treatment arm compared to the control arm across several endpoints. The success thresholds are defined within the study design.
| Performance Metric (Acceptance Criteria) | Reported Device Performance (Treatment Arm vs. Control Arm) |
|---|---|
| Primary Effectiveness: | |
| 90-day Utility Weighted Modified Rankin Scale (UW-mRS): Posterior probability the Trevo thrombectomy increases expected scores relative to medical management alone, with a threshold for success of at least 0.986. | Mean UW-mRS: 5.5 (Treatment) vs. 3.4 (Control) Posterior mean treatment benefit, core-adjusted: 2.0 (95% credible interval 1.1 to 3.0) Probability of superiority: > 0.9999 |
| 90-day Dichotomized mRS (0-2 vs. 3-6) (Functional Independence): Success based on the same model and hierarchical fashion as UW-mRS. | Functional Independence (mRS 0-2): 48.6% (Treatment) vs. 13.1% (Control) Posterior treatment benefit, core-adjusted: 32.8% (95% credible interval 21.1% to 44.1%) Probability of superiority: > 0.9999 |
| Primary Safety: | |
| Incidence of stroke-related mortality at 90 days: No significant difference between study arms. | Treatment Arm: 15.9% (17/107) vs. Control Arm: 18.2% (18/99) Difference: -2.3% [-12.6%, 8.0%] p-value = 0.7126 (No significant difference) |
| Secondary Effectiveness: | |
| Early Neurological Response (Day 5-7/Discharge): Defined as NIHSS drop of ≥ 10 points or NIHSS score of 0 or 1. | Treatment Arm: 47.7% vs. Control Arm: 19.2% Mean Absolute Difference: 28.5% (16.2%, 40.7%) Risk Ratio: 2.5 (1.6, 3.9) P-Value: <0.001 (Superiority for Treatment Arm) |
| Revascularization Rates at 24 Hours: Presence of partial or complete recanalization. | Treatment Arm: 76.6% (82/107) vs. Control Arm: 38.4% (38/99) Difference: 40.2% [27.1%, 51.5%] p-value: < 0.0001 (Superiority for Treatment Arm) |
| Secondary Safety: | |
| Incidence of sICH (by ECASS III definition) within 24 hours post-randomization: No statistical difference between arms. | Treatment Arm: 5.6% (6/107) vs. Control Arm: 3.0% (3/99) Difference: 2.6% [-2.9%, 8.1%] p-value = 0.5011 (No statistical difference) |
| Incidence of Neurological Deterioration (≥ 4-point increase in NIHSS from baseline through Day 5-7/Discharge): | Treatment Arm: 14.0% (15/107) vs. Control Arm: 26.3% (26/99) Difference: -12.2% [-23.1%, -1.4%] p-value = 0.0358 (Less frequently in Treatment Arm) |
| All-Cause Mortality at 90 days: No significant difference between study arms. | Treatment Arm: 18.7% (20/107) vs. Control Arm: 18.2% (18/99) Difference: 0.5% [-10.1%, 11.1%] p-value = 1.0000 (No statistical difference) |
| Serious Adverse Events (Procedure-related and Device-related): No new safety risks identified, comparable across treatment groups. | Vascular perforation: 0.9% (Treatment) Intramural arterial dissection: 1.9% (Treatment) Embolization to a new territory: 3.7% (Treatment) Full list in Table 11 & 12 No new safety risks identified, comparable risk profile to predicate. |
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: 206 subjects (107 in the Treatment Arm, 99 in the Control Arm).
- Data Provenance: The DAWN™ study (IDE G130223) was a "multi-center, ... conducted in multiple countries." The document doesn't specify the exact countries, but it indicates an international scope. The study was prospective, randomized, open, masked endpoint trial.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
The document mentions "masked endpoint trial" and "CEC adjudication" (Clinical Events Committee). While it confirms the involvement of a committee for adjudication, it does not specify the exact number of experts or their specific qualifications (e.g., number of years of experience, subspecialty) for establishing the ground truth.
4. Adjudication Method for the Test Set:
The exact adjudication method (e.g., 2+1, 3+1) is not explicitly stated. However, it refers to "CEC adjudication," indicating that a Clinical Events Committee independently reviewed and determined certain outcomes (e.g., sICH, neurological deterioration, all-cause mortality, serious adverse events). This typically implies a consensus-based approach among committee members.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
A multi-reader multi-case (MRMC) comparative effectiveness study was not performed as described in the document. The study was a randomized controlled trial comparing the Trevo thrombectomy device plus medical management to medical management alone. This is a direct patient outcome study, not a study of human readers' performance with or without AI assistance. The Trevo Retriever is a medical device for mechanical thrombectomy, not an AI diagnostic tool.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
This question is not applicable as the Trevo Retriever is a physical medical device (neurovascular mechanical thrombectomy device), not a standalone algorithm or AI. Its performance is directly measured in terms of patient outcomes and procedural metrics.
7. Type of Ground Truth Used:
The ground truth used in the DAWN study was based on patient outcomes data, specifically:
- Clinical Outcomes: Modified Rankin Scale (mRS) at 90 days (utility-weighted and dichotomized).
- Neurological Assessment: NIHSS scores (for early neurological response and deterioration).
- Imaging Data: Recanalization rates (CTA or MRA at 24 hours), core infarct volume (for inclusion criteria and statistical adjustment).
- Safety Endpoints: Stroke-related mortality, sICH (ECASS III definition), all-cause mortality, and adverse events (adjudicated by CEC).
8. Sample Size for the Training Set:
The document describes a clinical trial (DAWN study) to evaluate the device in general, not specifically an AI model with a separate training and test set. Therefore, there is no "training set" for an AI algorithm mentioned in the context of this device's premarket notification. The entire DAWN study cohort (206 subjects) served as the dataset for evaluating the device's effectiveness and safety.
9. How the Ground Truth for the Training Set Was Established:
As there is no "training set" for an AI algorithm, this question is not applicable. The clinical trial data was gathered through the rigorous protocol of the DAWN study, including masked endpoint assessment and CEC adjudication for relevant clinical and safety outcomes, which served as the "ground truth" for evaluating the device's performance in comparison to standard medical management.
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February 15, 2018
Concentric Medical, Inc. Rhoda M. Santos Senior Principal Regulatory Affairs Specialist 301 East Evelyn Avenue Mountain View, California 94041
Re: K173352
Trade/Device Name: Trevo ProVue Retriever and Trevo XP ProVue Retriever (Trevo Retriever) Regulation Number: 21 CFR 882.5600 Regulation Name: Neurovascular Mechanical Thrombectomy Device for Acute Ischemic Stroke Treatment Regulatory Class: Class II Product Code: POL, NRY Dated: January 12, 2018 Received: January 16, 2018
Dear Ms. Rhoda M. Santos:
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. 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 801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820);
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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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Carlos L. Pena -S
Carlos L. Peña, PhD, MS Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K173352
Device Name
Trevo ProVue Retriever and Trevo XP ProVue Retriever (Trevo Retriever)
Indications for Use (Describe)
-
The Trevo Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA). Endovascular therapy with the device should start within 6 hours of symptom onset.
-
The Trevo Retriever is intended to restore blood flow in the neurovasculature by removing thrombus in patients experiencing ischemic stroke within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.
-
The Trevo Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patient, proximal anterior circulation, large vessel occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 segments with smaller core infarcts (0-50 cc for age < 80 years, 0-20 cc for age ≥ 80 years). Endovascular therapy with the device should start within 6-24 hours of time last seen well in patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy.
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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510(k) Summary
| Trade Name: | Trevo ProVue Retriever and Trevo XP ProVue Retriever (Trevo Retriever) |
|---|---|
| Common Name: | Trevo Retriever |
| Classification Name: | Neurovascular Mechanical Thrombectomy Device for AcuteIschemic Stroke Treatment, 21 CFR 882.5600, Class II, POL -Percutaneous Catheter, 21CFR 870.1250, Class II, NRY |
| Product Code: | POL, NRY |
| Submitter: | Concentric Medical, Inc.301 E. Evelyn AvenueMountain View, CA 94041Tel 510-413-2269Fax 510-413-2558Facility Registration #2954917 |
| Contact: | Rhoda M. SantosSenior Principal Regulatory Affairs Specialist |
| Date Prepared: | February 6, 2018 |
| Predicate Device: | Trevo ProVue Retriever and Trevo XP ProVue Retriever(DEN150049) |
| Reference Predicate Device: | Trevo Retriever (K120961) |
Device Description
The Trevo Retriever family, including the Trevo ProVue and Trevo XP ProVue Retriever consists of a flexible, tapered core wire with a shaped section at the distal end. Platinum markers at the distal end allow fluoroscopic visualization. In addition, the shaped section is also radiopaque. Retriever dimensions are indicated on product label. The Retriever has a hydrophilic coating to reduce friction during use. The Retriever has a shaft marker to indicate proximity of Retriever tip relative to Microcatheter tip. A torque device is provided with the Retriever to facilitate manipulation. The torque device is used to lock the core wire to the microcatheter during the procedure. Locking of the torque device to the wire allows the microcatheter and Retriever to be retracted as a system during clot retrieval. An insertion tool is provided to introduce the Retriever into a Microcatheter. The Insertion Tool is a sheath in which the Retriever comes preloaded. Once half the retriever's length is inserted into the microcatheter, the insertion tool is removed. Retrievers have a modified proximal end that permits attachment of the Abbott Vascular DOC Guide Wire Extension (REF 22260). Joining Guide Wire Extension to Retriever facilitates removal or exchange of a catheter while maintaining Retriever position in anatomy. After exchange has been completed, the extension can be detached.
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Accessories
The Retriever is provided with two accessories: a torque device facilitates manipulation of the Retriever; and an insertion tool is used to introduce the Retriever into a microcatheter.
Indications for Use
The Indications for Use for the Trevo ProVue and Trevo XP ProVue Retrievers are as follows:
-
- The Trevo Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA). Endovascular therapy with the device should start within 6 hours of symptom onset.
-
- The Trevo Retriever is intended to restore blood flow in the neurovasculature by removing thrombus in patients experiencing ischemic stroke within 8 hours of symptom onset. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy are candidates for treatment.
-
- The Trevo Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 segments with smaller core infarcts (0-50 cc for age < 80 years, 0-20 cc for age ≥ 80 years). Endovascular therapy with the device should start within 6-24 hours of time last seen well in patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who fail IV t-PA therapy.
Technological Characteristics and Product Feature Comparison
The Trevo ProVue and Trevo XP ProVue Retriever subject devices are identical to the predicate devices and differ only by the expanded indications for use.
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| Feature | Reference PredicateDeviceTrevo Retriever(K120961) | Primary Predicate DeviceTrevo ProVue Retriever andTrevo XP ProVue Retriever(DEN150049) | Subject DeviceTrevo ProVue Retriever andTrevo XP ProVue Retrieverwith Expanded Indications | Rationale forModification (ifapplicable) |
|---|---|---|---|---|
| Intended Use | The Trevo Retriever isintended to restore bloodflow in theneurovasculature byremoving thrombus inpatients experiencingischemic stroke within 8hours of symptom onset.Patients who are ineligiblefor intravenous tissueplasminogen activator(IV-tPA) or who fail IV t-PA therapy are candidatesfor treatment. | Neurovascular mechanicalthrombectomy device for acuteischemic stroke treatment usedin the treatment of acuteischemic stroke to improveclinical outcomes. | Same | Not applicable. |
| Feature | Reference PredicateDeviceTrevo Retriever(K120961) | Primary Predicate DeviceTrevo ProVue Retriever andTrevo XP ProVue Retriever(DEN150049) | Subject DeviceTrevo ProVue Retriever andTrevo XP ProVue Retrieverwith Expanded Indications | Rationale forModification (ifapplicable) |
| Indications forUse | The Trevo Retriever isintended to restore bloodflow in theneurovasculature byremoving thrombus inpatients experiencingischemic stroke within 8hours of symptom onset.Patients who areineligible for intravenoustissue plasminogenactivator (IV-tPA) or whofail IV t-PA therapy arecandidates for treatment. | The Trevo Retriever isindicated for use to restoreblood flow in theneurovasculature by removingthrombus for the treatment ofacute ischemic stroke to reducedisability in patients with apersistent, proximal anteriorcirculation, large vesselocclusion, and smaller coreinfarcts who have first receivedintravenous tissue plasminogenactivator (IV-tPA).Endovascular therapy with thedevice should start within 6hours of symptom onset. | 1. The Trevo Retriever isindicated for use to restoreblood flow in theneurovasculature by removingthrombus for the treatment ofacute ischemic stroke to reducedisability in patients with apersistent, proximal anteriorcirculation, large vesselocclusion, and smaller coreinfarcts who have first receivedintravenous tissue plasminogenactivator (IV t-PA).Endovascular therapy with thedevice should start within 6hours of symptom onset.2. The Trevo Retriever isintended to restore blood flowin the neurovasculature byremoving thrombus in patientsexperiencing ischemic strokewithin 8 hours of symptomonset. Patients who areineligible for intravenoustissue plasminogen activator(IV t-PA) or who fail IV t-PAtherapy are candidates fortreatment.3. The Trevo Retriever isindicated for use to restoreblood flow in theneurovasculature by removingthrombus for the treatment ofacute ischemic stroke to reducedisability in patients with apersistent, proximal anteriorcirculation, large vesselocclusion of the internalcarotid artery (ICA) or middlecerebral artery (MCA)-M1segments with smaller coreinfarcts (0-50 cc for age < 80years, 0-20 cc for age ≥ 80years). Endovascular therapywith the device should startwithin 6-24 hours of time lastseen well in patients who areineligible for intravenoustissue plasminogen activator(IV t-PA) or who fail IV t-PAtherapy. | The results ofDAWN study(IDE G130223)demonstrate thatthe expandedindications do notraise any new ordifferentquestions ofsafety oreffectiveness. |
| REGULATORY INFORMATION | ||||
| RegulationNumber/Name/ Class/Product Code | 21 CFR 870.1250,Percutaneous Catheter,Class II, NRY | 21 CFR 882.5600,Neurovascular MechanicalThrombectomy Device forAcute Ischemic StrokeTreatment, Class II, POL | Same | Not applicable. |
| Feature | Reference PredicateDeviceTrevo Retriever(K120961) | Primary Predicate DeviceTrevo ProVue Retriever andTrevo XP ProVue Retriever(DEN150049) | Subject DeviceTrevo ProVue Retriever andTrevo XP ProVue Retrieverwith Expanded Indications | Rationale forModification (ifapplicable) |
| TargetPopulation | Patients experiencing acute ischemic stroke | Patients experiencing acute ischemic stroke | Same | Not applicable. |
| AnatomicalSites | Neurovasculature | Neurovasculature | Same | Not applicable. |
| TECHNOLOGICAL CHARACTERISTICS | ||||
| DeviceDescription | The Retriever consists ofa flexible, tapered corewire with a shaped sectionat the distal end. Aplatinum coil allowsfluoroscopic visualization.The Retriever has ahydrophilic coating toreduce friction. TheRetriever has a shaftmarker to indicateproximity of Retriever tiprelative to Microcathetertip. A torque device andinsertion tool are providedwith the Retriever. | The Retriever consists of aflexible, tapered core wire witha shaped section at the distalend. Platinum markers at thedistal end allow fluoroscopicvisualization. In addition, theshaped section is alsoradiopaque. Retrieverdimensions are indicated onproduct label. The Retriever hasa hydrophilic coating to reducefriction during use. TheRetriever has a shaft marker toindicate proximity of Retrievertip relative to Microcatheter tip.A torque device is providedwith the Retriever to facilitatemanipulation. The torque deviceis used to lock the core wire tothe microcatheter during theprocedure. Locking of thetorque device to the wire allowsthe microcatheter and Retrieverto be retracted as a systemduring clot retrieval. Aninsertion tool is provided tointroduce the Retriever into aMicrocatheter. The InsertionTool is a sheath in which theRetriever comes preloaded.Once half the retriever's lengthis inserted into themicrocatheter, the insertion toolis removed. Retrievers have amodified proximal end thatpermits attachment of theAbbott Vascular DOC GuideWire Extension (REF 22260).Joining Guide Wire Extensionto Retriever facilitates removalor exchange of a catheter whilemaintaining Retriever positionin anatomy. After exchange hasbeen completed, the extensioncan be detached. | Same | Not applicable. |
| Principle ofOperation | The Trevo Retriever is delivered to the thrombus using amicrocatheter. The microcatheter is then retracted to deploythe shaped section of the Retriever. The Retriever andMicrocatheter are pulled back to capture the thrombus. TheRetriever, thrombus and Microcatheter are then removed | Same | Not applicable. |
Table 1: Product Feature Comparison of Subject Device to Predicate Device
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| Feature | Reference PredicateDeviceTrevo Retriever(K120961) | Primary Predicate DeviceTrevo ProVue Retriever andTrevo XP ProVue Retriever(DEN150049) | Subject DeviceTrevo ProVue Retriever andTrevo XP ProVue Retrieverwith Expanded Indications | Rationale forModification (ifapplicable) | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sizes | 4x20mm | 3x20mm, 4x20mm, 4x30mm,6x25mm | Same | Not applicable. | ||||||||||||||||||||||
| AccessoryDevices | Insertion tool and torque device provided within productpackage | Same | Not applicable. | |||||||||||||||||||||||
| Microcatheter(MC)Compatibility | Retriever size Trevo 18MC Trevo ProVue4X20mm ✓ | Retrieversize TrevoPro14MC TrevoPro18MC Trevo XPProVue3X20mm ✓ ✓ Trevo XPProVue4X20mm ✓ TrevoProVue4X20mm ✓ Trevo XPProVue4X30mm ✓ Trevo XPProVue6X25mm ✓ | Excelsior® XT-27®Microcatheters(150cm x6cmstraightREF275081) | Not applicable. | ||||||||||||||||||||||
| Materials | ||||||||||||||||||||||||||
| Core Wire | Nitinol (nickel titanium alloy) | Same | Not applicable. | |||||||||||||||||||||||
| Shaped Section | Nitinol | Same | Not applicable. | |||||||||||||||||||||||
| Distal Coil | Platinum/Tungsten | Same | Not applicable. | |||||||||||||||||||||||
| Shaped SectionRadiopaqueWire | Not applicable. | Platinum/Tungsten | Same | Not applicable. | ||||||||||||||||||||||
| Proximal Coil | 304 Stainless Steel | Same | Not applicable. | |||||||||||||||||||||||
| Solder | Gold/Tin | Same | Not applicable. | |||||||||||||||||||||||
| HydrophilicCoating | Sodium hyaluronate mixture | Same | Not applicable. |
Risk Assessment
Risk assessment of the modifications has been conducted in accordance with EN ISO 14971:2012. Concentric Medical, Inc. has determined that the expanded indications raise no new questions of safety or effectiveness. Results of clinical testing are appropriate for use in determining that the subject device is substantially equivalent to the predicate device.
The expanded indications did not result in the identification of any new failure modes nor were there any changes to existing failure modes, including no change to severity or occurrence; and, therefore, no change to overall residual risk.
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Leveraged Non-Clinical Data
Performance testing for the subject device is leveraged from the predicate device cleared under reclassification order DEN150049 and the reference predicate device cleared under K120961. The subject device (Trevo ProVue and Trevo XP ProVue Retrievers with Expanded Indications) differs from the predicate devices (DEN150049, K120961) only by the indications for use. The technological characteristics and principles of operation remain unchanged. There are no changes in the device design, materials, manufacturing, packaging and sterilization methods, therefore biocompatibility data, bench-top data, sterilization and stability data from the predicate devices (DEN150049, K120961) are directly applicable and no additional testing is required or was performed.
Clinical Data
The DAWN™ study (IDE G130223) was a multi-center, Bayesian adaptive-enrichment, prospective, randomized, open, masked endpoint trial, conducted in multiple countries to evaluate the safety and effectiveness of the subject device with the expanded indications. The data from the DAWN study constitutes the premarket clinical data required to demonstrate substantial equivalence with the predicate device.
Study Design
The DAWN study was designed to evaluate the hypothesis that Trevo thrombectomy plus medical management leads to superior clinical outcomes at 90 days as compared to medical management alone in appropriately selected subjects experiencing an acute ischemic stroke when treatment is initiated within 6-24 hours after last seen well; 90-day disability assessed by modified Rankin scale (mRS) is the primary endpoint.
The first co-primary analysis, based on the utility weighted (UW)-mRS, evaluated the posterior probability the Trevo thrombectomy increases expected scores relative to medical management alone, using a statistical model that adjusts for baseline core infarct volume. The threshold for success was a posterior probability of at least 0.986, increased from 0.975 to account for the potential for enrichment and different final sample sizes. The second co-primary analysis based on the dichotomized mRS (0-2 vs. 3-6) was conducted in the same model and carried out in a hierarchical fashion. The trial had 86% power to detect a UW-mRS difference of 1.0 between the treatment arms. Study success was predicated on simultaneous success of the co-primary endpoint analyses.
Key Inclusion Criteria
Acute ischemic stroke with confirmed occlusion of intracranial ICA and/or M1, that failed or were contraindicated for IV t-PA, treatment within 6-24 hours after time last known well, baseline NIHSS > 10, informed consent given and age 18 or over; In patients younger than 80, a stroke score equal to or greater than 10 must be associated with a core volume less than 51 ml. In patients 80 or older, the stroke score must be greater than 10 and volume less than 21 ml. Clinical-core mismatch which is defined as the mismatch between baseline infarct volume (or core) on CT or MRI imaging and the extent of total brain tissue at risk.
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Key Exclusion criteria
Rapid improvement in neurological status to an NIHSS < 10 or evidence of vessel recanalization prior to randomization; Arterial blood pressure > 185/110 mmHg; laboratory evidence of electrolyte imbalance (i.e., sodium < 130 mmol/L, potassium < 3 mEq/L or > 6 mEq/L); laboratory evidence of renal failure (i.e., serum creatinine > 3.0 mg/dL (264 umol/L); laboratory evidence of coagulation abnormalities (i.e., platelet count < 50,000/uL, APTT > 3 times normal or INR > 3.0, if given factor Xa inhibitor 24-48 hours ago must have normal PTT); laboratory evidence of bleeding (i.e., hemoglobin < 7 mmol/L).
Primary Effectiveness Analysis
Study success was based on simultaneous success criteria of both the 90 day UW-mRS as well as the dichotomized 90 day mRS (0-2 vs. 3-6) of the ITT population. Table 2 shows the overall distribution and descriptive statistics of the 90 day mRS. In all analyses, outcomes for the Treatment arm were significantly better than the Control arm.
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| Modified Rankin Scale (mRS) | Treatment ArmN=107 | Control ArmN= 99 |
|---|---|---|
| 0 - No symptoms / UW = 10 | 9.3% (10/107) | 4.0% (4/99) |
| 1 - No significant disability / UW = 9.1 | 22.4% (24/107) | 5.1% (5/99) |
| 2 - Slight disability / UW = 7.6 | 16.8% (18/107) | 4.0% (4/99) |
| 3 - Moderate disability / UW = 6.5 | 13.1% (14/107) | 16.2% (16/99) |
| 4 - Moderately severe disability / UW= 3.3 | 13.1% (14/107) | 34.3% (34/99) |
| 5 - Severe disability / UW = 0 | 6.5% (7/107) | 18.2% (18/99) |
| 6 - Dead / UW = 0 | 18.7% (20/107) | 18.2% (18/99) |
| 90 Day mRS [0-2] | 48.6% (52/107) | 13.1% (13/99) |
| 90 Day Weighted mRS** | ||
| Mean $\pm$ SD (N) | 5.5 $\pm$ 3.8 (107) | 3.4 $\pm$ 3.2 (99) |
| Median (Q1, Q3) | 6.5 (0.0, 9.1) | 3.3 (0.0, 6.5) |
| Range(min, max) | (0.0, 10.0) | (0.0, 10.0) |
| [95% Conf. Interval]¹ | [4.8, 6.3] | [2.7, 4.0] |
| ¹ By normal approximation** mRS =(0,1,2,3,4,5,6) was assigned a corresponding numerical value =(10,9.1,7.6,6.5,3.3,0,0), whichrepresents its clinical utility |
Table 2: 90 Day Imputed Modified Rankin Scale ITT Population
Table 3 summarizes the co-primary outcomes. The mean value of UW-mRS was 5.5 in the Treatment group and 3.4 in the Control group. The core infarct adjusted posterior mean treatment benefit of the ITT analysis population was 2.04 with 95% Credible Interval 1.1 to 2.98. The Treatment arm had superior rates of functional independence at 90 days (48.6 % vs. 13.1%); core adjusted posterior treatment benefit of 32.8%, 95% Credible Interval 21.1% to 44.1%. The posterior probability of superiority for both coprimary endpoints was highly significant at > 0.9999.
Table 3: Co-Primary outcomes ITT population
| Outcome | TrevoArm(N=107) | ControlArm(N=99) | Mean AbsoluteDifference(95% CI) | Posterior meanbenefit,core-adjusted(95% credibleinterval) * | Probability ofsuperiority |
|---|---|---|---|---|---|
| Utility-Weighted mRS-mean (SD) | 5.5 (3.8) | 3.4 (3.1) | 2.1(1.2, 3.1) | 2.0(1.1, 3.0) | >0.99991 |
| Functional Independence (mRS 0-2) | 48.6% | 13.1% | 35.5%(23.9%, 47.0%) | 32.8%(21.1%, 44.1%) | >0.9999 |
*Estimated by Bayesian general linear model adjusting for Core Infarct
1The overall probability of a device benefit is then the average of the benefit probabilities for the imputed by the imputation probabilities of those data sets. This probability is 0.999986.
To provide additional context, the UW-mRS expected benefit of 2.04 represents 20.4% of the total value of preventing a single death and, instead, achieving a normal neurologic
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outcome for that individual patient. Accordingly, the number needed to treat to save one life is 10/2.04 = 4.9 (95% credible interval 3.4-9.1). This value indicates that 4.9 patients need to be treated with Trevo thrombectomy rather than medical care alone for the accrued benefit to equal saving one life with return to normal function. Additionally, the number needed to treat to achieve functional independence (90-day mRS 0-2) is 2.8.
Primary Endpoint by Time
The randomization stratification of the DAWN Trial included a stratification variable of 6-12 hours and 12-24 hours to ensure balance of randomization across time. The minimum and maximum TLSW were 6.1 to 23.9 hours demonstrating subjects across the entire intended time spectrum were enrolled.
Figure 1 below plots the unadjusted probability of 90 day functional independence (mRS 0-2) by TLSW, demonstrating durability of treatment benefit across the 12-24 hour time spectrum.
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Image /page/13/Figure/1 description: The image is a graph titled "Functional Independence (mRS 0-2) by Time Since Time Last Seen Well To Randomization". The x-axis is labeled "Time since time last seen well to randomization (hrs)" and ranges from 5 to 25. The y-axis is labeled "Estimated Probability" and ranges from 0.0 to 1.0. There are two lines on the graph, one blue and one red, representing different treatment assignments, MM and Trevo, respectively.
Figure 1: Functional Independence (mRS 0-2) by TLSW
Table 4 further sub-groups 90 day functional independence (mRS 0-2) by 3 hour intervals. Although some intervals (i.e. 18-21 and 21-24 hours) had small numbers, the benefit of thrombectomy as measured by absolute difference was observed in each subgroup.
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| TLSW Intervals | Treatment | Control | Difference | P-value |
|---|---|---|---|---|
| 6-9 hrs | 50.0% (9/18) | 14.3% (3/21) | 35.7%[ 8.2%, 63.2%] | 0.0346a |
| 9-12 hrs | 58.1 % (18/31) | 26.1%(6/24) | 33.1% [8.5%,57.6%] | 0.0273 a |
| 6-12 hrs Total | 55.1% (27/49) | 20.0% (9/45) | 35.1%[ 16.9%, 53.3%] | 0.0006a |
| 12-15 hrs | 37.5% (6/16) | 9.1% (2/22) | 28.4%[1.8%,55.0%] | 0.0498a |
| 15-18 hrs | 50.0% (13/26) | 5.3% (1/19) | 44.7%[ 23.1%, 66.4%] | 0.0025a |
| 18-21 hrs | 36.4% (4/11) | 0.0% (0/8) | 36.4%[ 7.9%, 64.8%] | 0.1032a |
| 21-24 hrs | 40.0% (2/5) | 20.0% (1/5) | 20.0%[-35.4%,75.4%] | 1.0000a |
| 12-24 Total* | 43.1% (25/58) | 7.4% (4/54) | 35.7%[ 21.2%, 50.2%] | < 0.0001a |
Table 4: Functional independence (90 Day mRS 0-2) Sub-grouped by Time
a.. Fisher's exact test
- Greater level of uncertainty in the results shown for subjects in the 18-24 hour time from last seen well. The p-value was not adjusted for multiplicity.
Secondary Effectiveness Outcome: Vessel Perfusion Rates
The proportion of subjects with early Neurological response at Day 5-7/Discharge (whichever was earlier), was also assessed. This endpoint was defined as a NIHSS drop of ≥ 10 points from baseline or an NIHSS score of 0 or 1. Table 5 exhibits this acute improvement in the NIHSS scores among Treatment Arm subjects when compared with Control Arm subjects.
| Table 5: Early Neurological Response at Dav 5-7/Discharge | ||
|---|---|---|
| Outcome | InterventionN=107 | ControlN=99 | Mean AbsoluteDifference(95% CI) | Risk Ratio(95% CI) | P-Value |
|---|---|---|---|---|---|
| Early Response† | 47.7% | 19.2% | 28.5% (16.2%, 40.7%) | 2.5 (1.6, 3.9) | <0.001 |
† Defined as NIHSS drop of ≥ 10 points from baseline or NIHSS 0 or 1 at day 5-7 or discharge (whichever was earlier)
The p-value was not adjusted for multiplicity.
Secondary Effectiveness Outcome: Revascularization Rates at 24 Hours
Recanalization of the qualifying occlusive lesion on the 24-hour follow-up CTA or MRA scans was also analyzed. Vessel occlusion status on CTA or MRA at 24 hours was characterized by the imaging core laboratory according to a scale ranging from 0 (no recanalization) to 1 (partial recanalization) to 2 (complete recanalization). Revascularization at 24 hours was defined as the presence of partial or complete recanalization. If the initially occluded MCA-M1 segment was found to be completely or partially recanalized on follow-up CTA or MRA but both MCA-M2 divisions remained occluded, recanalization was considered as unsuccessful. For reference, the Post
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procedure mTICI > 2b was 84.8% in the Treatment arm. Revascularization rates are shown in Table 6. The absolute difference in revascularization at 24 hours was 40.2% demonstrating superiority of Trevo thrombectomy compared to standard of care medical management (p<0.0001).
| TotalN=206 | TreatmentArmN=107 | ControlArmN= 99 | Difference[95% CI] | p-value | |
|---|---|---|---|---|---|
| Difference in revascularization ratesat 24 (-6/+24) hours fromrandomization | 58.7%(121/206) | 76.6%(82/107) | 38.4%(38/99) | 40.2%[27.1%, 51.5%] | < 0.0001a |
Table 6: Revascularization rates at 24 hours
Revascularization at 24 hours was defined as the presence of partial or complete recanalization. a. Fisher's exact test. The p-value was not adjusted for multiplicity.
Primary and Secondary Safety Outcomes
The primary safety endpoint was the incidence of stroke-related mortality at 90 days. The secondary safety outcomes for both Treatment and Control Arms are incidence of sICH, by ECASS III definition, within 24 (-6/+24) hours post randomization, and incidence of neurological deterioration from baseline NIHSS score through Day 5- 7/discharge (whichever is earlier) post randomization. Neurological deterioration was defined as ≥ 4 point increase in the NIHSS score from the baseline score.
Primary Safety Outcome: Incidence of Stroke-Related Mortality at 90 days The primary safety endpoint is incidence of stroke-related mortality at 90 days. In total, 17.0% (35/206) of the study subjects had stroke-related mortality within 90 days of enrollment into study: 15.9% (17/107) in the Treatment Arm and 18.2% (18/99) in the Control Arm. Stroke-related mortality rates at 90 days did not differ significantly (p= 0.7126) between study arms, as shown in Table 7.
Table 7: Stroke-Related Mortality at 90 Days
| TotalN=206 | Treatment ArmN=107 | Control ArmN= 99 | Difference[95% CI]¹ | p-value | |
|---|---|---|---|---|---|
| Incidence of all stroke-relatedmortality at 90 days | 17.0% (35/206) | 15.9% (17/107) | 18.2% (18/99) | -2.3%[-12.6%,8.0%] | 0.7126a |
¹ By normal approximation
a. Fisher's exact test. The p-value was not adjusted for multiplicity.
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Secondary Safety Outcome: Incidence of sICH
Incidence of sICH, by ECASS III definition, within 24 (-6/+24) hours post randomization (time zero) was assessed in both study arms. These results are shown in Table 8.
| TotalN=206 | TreatmentArmN=107 | Control ArmN= 99 | Difference[95% CI]1 | p-value | |
|---|---|---|---|---|---|
| sICH at 24 (-6/+24) hrs postrandomization | 4.4% (9/206) | 5.6% (6/107) | 3.0% (3/99) | 2.6%[-2.9%, 8.1%] | 0.5011a |
Table 8: Incidence of sICH by CEC Adjudication
¹ By normal approximation
a. Fisher's exact test. The p-value was not adjusted for multiplicity.
The CEC adjudicated sICH in 4.4% (9/206) of subject cases: 5.6% (6/107) in the Treatment Arm and 3.0% (3/99) in the Control Arm. There was no statistical difference in sICH rates between arms. There was also no difference in the occurrence of sICH relative to TLSW between the Treatment arm and Control arm. The average TLSW for Treatment arm subjects with sICH was 13.4 + 4.6 hours and 8.1 + 2.3 hours in the control arm (p=0.11). For reference, the published rates from a large meta-analysis of over 1200 patients, sICH rates within 6 hours of TLSW are 4.4% for thrombectomy and 4.3% for medical management.
Secondary Safety Outcome: Incidence of Neurological Deterioration
Incidence of neurological deterioration was defined as a ≥ 4 point increase in the NIHSS score from baseline through Day 5-7/Discharge post randomization.
As presented in Table 9. neurological deterioration was reported in 19.9% (41/206) of subject cases with 14.0% (15/107) of the cases in the Treatment Arm and 26.3% (26/99) in the Control Arm per CEC adjudication, with a p-value of 0.0358.
Table 9: Incidence of Neurological Deterioration by CEC Adjudication
| TotalN=206 | TreatmentArmN=107 | Control ArmN= 99 | Difference[95% CI]1 | p-value | |
|---|---|---|---|---|---|
| Incidence of neurologicaldeterioration between baselineand Day 5 to 7/Discharge | 19.9% (41/206) | 14.0% (15/107) | 26.3% (26/99) | -12.2%[-23.1%, -1.4%] | 0.0358a |
¹ By normal approximation
a. Fisher's exact test. The p-value was not adjusted for multiplicity.
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Secondary Safety Outcome: Difference of All-Cause Mortality by CEC Adjudication The difference between the two study arms in all-cause mortality rates up to and including 90 day follow-up was also assessed based upon CEC adjudication. Overall, in the study 18.4% (38/206) of subjects expired within 90 days of enrollment; 18.7% (20/107) in the Treatment Arm and 18.2% (18/99) in the Control Arm (p=1.0). These data are presented in Table 10.
| TotalN=206 | Treatment ArmN=107 | Control ArmN= 99 | Difference[95% CI]1 | p-value | |
|---|---|---|---|---|---|
| Incidence of all-causemortality at 90 days | 18.4% (38/206) | 18.7% (20/107) | 18.2% (18/99) | 0.5%[-10.1%, 11.1%] | 1.0000a |
Table 10: Incidence of All-Cause Mortality by CEC Adjudication
1 By normal approximation
a. Fisher's exact test. The p-value was not adjusted for multiplicity.
Secondary Safety Outcome: Serious Adverse Events
Additional secondary safety outcome were defined as the incidence of procedure-related and device-related serious adverse events (PRSAEs and DRSAEs) through 24 (-6/+24) hours post randomization (time zero). All events were adjudicated by the Clinical Events Committee (CEC). This Safety Outcome, in the Treatment Arm, is provided in Table 11.
| Device Related%(n/N)[95% Conf. Interval]2 | Procedure Related%(n/N)[95% Conf.Interval]2 | TotalN=107%(n/N)[95% Conf. Interval]2 | |
|---|---|---|---|
| Vascular perforation | 0.0% (0/107) [0.0%, 3.4%] | 0.9% (1/107) [0.0%,5.1%] | 0.9% (1/107) [0.0%, 5.1%] |
| Intramural arterial dissection | 0.0% (0/107) [0.0%, 3.4%] | 1.9% (2/107) [0.2%,6.6%] | 1.9% (2/107) [0.2%, 6.6%] |
| Access site complication requiringsurgical repair or blood transfusion | 0.0% (0/107) [0.0%, 3.4%] | 0.9% (1/107) [0.0%,5.1%] | 0.9% (1/107) [0.0%, 5.1%] |
| Intra-procedural mortality | 0.0% (0/107) [0.0%, 3.4%] | 0.0% (0/107) [0.0%,3.4%] | 0.0% (0/107) [0.0%, 3.4%] |
| Device failure (in vivo breakage) | 0.0% (0/107) [0.0%, 3.4%] | 0.0% (0/107) [0.0%,3.4%] | 0.0% (0/107) [0.0%, 3.4%] |
| Embolization to a new territory | 3.7% (4/107) [1.0%, 9.3%] | 3.7% (4/107) [1.0%,9.3%] | 3.7% (4/107) [1.0%, 9.3%] |
| Any other complications adjudicated bythe CEC to be related to the procedure1 | 0.0% (0/107) [0.0%, 3.4%] | 0.9% (1/107) [0.0%,5.1%] | 0.9% (1/107) [0.0%, 5.1%] |
Table 11: Safety Outcome in Treatment Arm by CEC adjudication
1 One event of pulmonary edema in one subject (19900226) occurred during the procedure and was unrelated to the device but the relatedness to procedure could not be determined by CEC. The event is counted as procedure related.
2 Exact Clopper Pearson confidence intervals
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Table 12 presents a summary of all serious and non-serious adverse events for all Control Arm and Treatment Arm subjects by MedDRA Dictionary System Organ Classes (SOC).
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| Treatment arm N= 107 | Control Arm N= 99 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MedDRA* System OrganClass | SAEs | SubjectswithSAEs | NonSAEs | Subjectswith NonSAEs | TotalAEs | SubjectswithTotal AEs | SAEs | SubjectswithSAEs | NonSAEs | Subjectswith NonSAEs | TotalAEs | Subjects withTotal AEs |
| Any Adverse Event(AE) | 65 | 41(38.3%) | 476 | 102(95.3%) | 541 | 103(96.3%) | 83 | 47(47.5%) | 473 | 91(91.9%) | 556 | 91 (91.9%) |
| Blood and lymphatic systemdisorders | 0 | 0 | 11 | 10 (9.3%) | 11 | 10 (9.3%) | 1 | 1 (1.0%) | 8 | 8 (8.1%) | 9 | 8 (8.1%) |
| Cardiac disorders | 8 | 7 (6.5%) | 37 | 29(27.1%) | 45 | 33(30.8%) | 6 | 5 (5.1%) | 29 | 24(24.2%) | 35 | 28 (28.3%) |
| Endocrine disorders | 0 | 0 | 1 | 1 (0.9%) | 1 | 1 (0.9%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Eye disorders | 1 | 1 (0.9%) | 0 | 0 | 1 | 1 (0.9%) | 0 | 0 | 2 | 2 (2.0%) | 2 | 2 (2.0%) |
| Gastrointestinal disorders | 7 | 6 (5.6%) | 42 | 30(28.0%) | 49 | 34(31.8%) | 12 | 11(11.1%) | 38 | 28(28.3%) | 50 | 34 (34.3%) |
| General disorders andadministration siteconditions | 0 | 0 | 22 | 18(16.8%) | 22 | 18(16.8%) | 0 | 0 | 17 | 15(15.2%) | 17 | 15 (15.2%) |
| Hepatobiliary disorders | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 (1.0%) | 1 | 1 (1.0%) |
| Immune system disorders | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 (1.0%) | 1 | 1 (1.0%) |
| Infections and infestations | 6 | 6 (5.6%) | 46 | 34(31.8%) | 52 | 38(35.5%) | 7 | 7 (7.1%) | 54 | 41(41.4%) | 61 | 43 (43.4%) |
| Injury, poisoning andprocedural complications | 2 | 2 (1.9%) | 8 | 7 (6.5%) | 10 | 9 (8.4%) | 2 | 2 (2.0%) | 8 | 6 (6.1%) | 10 | 7 (7.1%) |
| Investigations | 0 | 0 | 5 | 5 (4.7%) | 5 | 5 (4.7%) | 0 | 0 | 10 | 10(10.1%) | 10 | 10 (10.1%) |
| Metabolism and nutritiondisorders | 0 | 0 | 76 | 47(43.9%) | 76 | 47(43.9%) | 0 | 0 | 62 | 34(34.3%) | 62 | 34 (34.3%) |
| Musculoskeletal andconnective tissue disorders | 0 | 0 | 11 | 10 (9.3%) | 11 | 10 (9.3%) | 2 | 2 (2.0%) | 22 | 15(15.2%) | 24 | 16 (16.2%) |
| Neoplasms benign,malignant and unspecified | 0 | 0 | 1 | 1 (0.9%) | 1 | 1 (0.9%) | 0 | 0 | 0 | 0 | 0 | 0 |
| Nervous system disorders | 21 | 21(19.6%) | 95 | 63(58.9%) | 116 | 71(66.4%) | 34 | 30(30.3%) | 88 | 53(53.5%) | 122 | 66 (66.7%) |
| Psychiatric disorders | 1 | 1 (0.9%) | 26 | 24(22.4%) | 27 | 24(22.4%) | 2 | 2 (2.0%) | 30 | 27(27.3%) | 32 | 28 (28.3%) |
| Renal and urinary disorders | 0 | 0 | 18 | 15(15.2%) | 18 | 15(15.2%) | 1 | 1 (1.0%) | 19 | 14(14.1%) | 20 | 15 (15.2%) |
| MedDRA* System OrganClass | Treatment arm N= 107 | Control Arm N= 99 | ||||||||||
| SAEs | SubjectswithSAEs | NonSAES | Subjectswith NonSAES | TotalAEs | SubjectswithTotal AEs | SAEs | SubjectswithSAEs | NonSAES | SubjectswithNonSAES | TotalAEs | Subjects withTotal AEs | |
| Reproductive system andbreast disorders | 0 | 0 | 1 | 1 (0.9%)(14.0%) | 1 | 1 (0.9%)(14.0%) | 0 | 0 | 2 | 2 (2.0%)(14.1%) | 2 | 2 (2.0%) |
| Respiratory, thoracic andmediastinal disorders | 14 | 11(10.3%) | 33 | 28(26.2%) | 47 | 33(30.8%) | 11 | 9 (9.1%) | 42 | 34(34.3%) | 53 | 37 (37.4%) |
| Skin and subcutaneoustissue disorders | 0 | 0 | 3 | 3 (2.8%) | 3 | 3 (2.8%) | 0 | 0 | 10 | 7 (7.1%) | 10 | 7 (7.1%) |
| Surgical and medicalprocedures | 1 | 1 (0.9%) | 1 | 1 (0.9%) | 2 | 2 (1.9%) | 1 | 1 (1.0%) | 2 | 2 (2.0%) | 3 | 3 (3.0%) |
| Vascular disorders | 4 | 3 (2.8%) | 39 | 33(30.8%) | 43 | 34(31.8%) | 4 | 4 (4.0%) | 28 | 21(21.2%) | 32 | 23 (23.2%) |
Table 12: MedDRA SOC Categorization of all Adverse Events in Both Study Arms (Site Reported)
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*MedDRA v17.0 was used.
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Safety Summary
No differences were observed in 90-day stroke-related mortality, 90-day all-cause mortality, or sICH, while neurologic deterioration occurred less frequently in the thrombectomy than in the control group. All serious adverse events, were comparable across the treatment groups. The SOC of Nervous System Disorders had the highest rate of SAEs with 19.6% of subjects in the Treatment arm and was 30.3% of the subjects in the Control arm.
No new safety risks were identified in the DAWN Trial expanded indication population. The risks to health associated with the use of the Trevo Retrievers for this additional indication are similar to those associated with the use of the Trevo Retrievers for the currently cleared indications.
Conclusion
The results of the co-primary analysis and supporting data from this RCT demonstrate use of Trevo Retrievers to treat ischemic stroke by restoring blood flow and reducing the incidence of disability is safe and effective in patients treated 6-24 hours since TLSW. Furthermore, the UW-mRS expected benefit of 2.04 represents 20.4% of the total value of preventing a single death and, instead, achieving a normal neurologic outcome for that individual patient. Accordingly, the number needed to treat to save one life is 10/2.04 = 4.9 (95% credible interval 3.4-9.1). This value indicates that 4.9 patients need to be treated with Trevo thrombectomy rather than medical care alone for the accrued benefit to equal saving one life with return to normal function. The number needed to treat to achieve functional independence is 2.8, demonstrating a superior therapy for a patient population with very poor prognosis.
Summary of Substantial Equivalence
As supported by the DAWN study (IDE G130223), the data demonstrated that the expanded indications for use for the subject device do not raise any new or different questions of safety or effectiveness nor do they have the potential to significantly increase a safety or effectiveness concern raised by the predicate device. The subject and predicate device have identical principles of operations and technological characteristics. The Trevo ProVue and Trevo XP ProVue Retriever with expanded indications (subject device) is therefore substantially equivalent to the cleared predicate device.
§ 882.5600 Neurovascular mechanical thrombectomy device for acute ischemic stroke treatment.
(a)
Identification. A neurovascular mechanical thrombectomy device for acute ischemic stroke treatment is a prescription device used in the treatment of acute ischemic stroke to improve clinical outcomes. The device is delivered into the neurovasculature with an endovascular approach, mechanically removes thrombus from the body, and restores blood flow in the neurovasculature.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The patient contacting components of the device must be demonstrated to be biocompatible.
(2) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use, including:
(i) Mechanical testing to demonstrate the device can withstand anticipated tensile, torsional, and compressive forces.
(ii) Mechanical testing to evaluate the radial forces exerted by the device.
(iii) Non-clinical testing to verify the dimensions of the device.
(iv) Non-clinical testing must demonstrate the device can be delivered to the target location in the neurovasculature and retrieve simulated thrombus under simulated use conditions.
(v) Non-clinical testing must demonstrate the device is radiopaque and can be visualized.
(vi) Non-clinical testing must evaluate the coating integrity and particulates under simulated use conditions.
(vii) Animal testing must evaluate the safety of the device, including damage to the vessels or tissue under anticipated use conditions.
(3) Performance data must support the sterility and pyrogenicity of the patient contacting components of the device.
(4) Performance data must support the shelf-life of the device by demonstrating continued sterility, package integrity, and device functionality over the specified shelf-life.
(5) Clinical performance testing of the device must demonstrate the device performs as intended for use in the treatment of acute ischemic stroke and must capture any adverse events associated with the device and procedure.
(6) The labeling must include:
(i) Information on the specific patient population for which the device is intended for use in the treatment of acute ischemic stroke, including but not limited to, specifying time from symptom onset, vessels or location of the neurovasculature that can be accessed for treatment, and limitations on core infarct size.
(ii) Detailed instructions on proper device preparation and use for thrombus retrieval from the neurovasculature.
(iii) A summary of the clinical testing results, including a detailed summary of the device- and procedure-related complications and adverse events.
(iv) A shelf life.