(91 days)
The DENALI® Filter System - Femoral and Jugular/Subclavian Delivery Kits are indicated for use in the prevention of recurrent pulmonary embolism via placement in the vena cava in the following situations:
- Pulmonary thromboembolism when anticoagulants are contraindicated. .
- . Failure of anticoagulant therapy for thromboembolic disease.
- . Emergency treatment following massive pulmonary embolism where anticipated benefits of conventional therapy are reduced.
- . Chronic, recurrent pulmonary embolism where anticoagulant therapy has failed or is contraindicated.
DENALI® Filter may be removed according to the instructions supplied under the section labeled: Optional Procedure for Filter Removal.
The DENALI® Filter consists of twelve Nitinol appendages emanating from a central snareable tip. These twelve appendages (six legs and six arms) form two levels of filtration for emboli: the legs provide the lower level of filtration and the arms provide the upper level of filtration. Four out of the six legs have cranial anchors and the remaining two legs have caudal anchors. In addition, all of the legs have penetration limiters. The anchors have been designed to resist cranial and caudal migration, while allowing the filter to be percutaneously removed. The DENALI® Filter is intended to be used in the inferior vena cava with diameters less than or equal to 28 mm.
The DENALI® Delivery Systems consist of an introducer sheath and dilator, and a preloaded DENALI® Filter in a storage tube with a pusher. The dilator accepts a 0.035" guidewire and allows for an 800 psi maximum pressure contrast power injection. Radiopaque marker bands are on the end of the dilator to aid in measuring the maximum indicated IVC diameter. They are spaced at a distance of 28 mm (outer-to-outer). The 55 cm, 8.4 French I.D. introducer sheath contains a radiopaque marker band at the distal tip and hemostasis valve with a side port. The pusher advances the filter through the introducer sheath to the pre-deployment mark and is then used to fix the filter in place while the filter is unsheathed.
The DENALI® Filter System's acceptance criteria and performance are detailed across various tests, including in-vitro, in-vivo animal studies, and a clinical study.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria Category | Specific Criteria/Endpoint | Acceptance Goal | Reported Device Performance |
|---|---|---|---|
| Clinical Efficacy (CSP) | Clinical Success Placement (CSP) | Lower bound of the 95% confidence interval for CSP was greater than 80%. | CSP was 96.1%, and the lower bound of the 95% confidence interval was 91.2%. Goal Met. |
| Clinical Efficacy (TSP) | Technical Success of Placement (TSP) | Not explicitly quantified as a percentage goal, but satisfactory deployment. | TSP was 100%. Goal Met. |
| Filter Retrieval | Retrieval Success Rate | All filters successfully removed with acceptable retrieval force (in animal study). | Animal Study: All 12 filters successfully removed with acceptable retrieval force. Clinical Study: 97.7% (86/88) retrieval success rate. Goal Met. |
| Safety (Animal Study) | Caval occlusion/thrombosis | No observed. | No observed caval occlusion/thrombosis. Goal Met. |
| IVC penetrations/perforations | No definitive. | No definitive IVC penetrations/perforations. Goal Met. | |
| Contrast extravasation | No extravasation from VC after filter removal. | No contrast extravasation from the VC after filter removal. Goal Met. | |
| Significant filter tilting | No significant. | No significant filter tilting. Goal Met. | |
| Hemodynamically significant caval stenosis | No. | No hemodynamically significant caval stenosis. Goal Met. | |
| Safety (Clinical Study) | Recurrent PE | Low incidence, non-fatal. | 2 / 139 (1.4%) symptomatic PEs, neither caused patient death. Goal Met. |
| Caval Occlusion | 0% | 0 / 137 (0%). Goal Met. | |
| Filter Fracture | 0% | 0 / 137 (0%). Also, no findings of filter fracture in the clinical study. Goal Met. | |
| Cranial Migration | 0% | 0 / 137 (0%). Also, no findings of cranial migration in the clinical study. Goal Met. | |
| Caudal Migration | 0% | 0 / 137 (0%). | |
| Filter Tilt at Placement | 0% | 0 / 175 (0%). Also, no findings of filter tilt at placement in the clinical study. Goal Met. | |
| Filter Tilt at Retrieval | 0% | 0 / 88 (0%). Also, no findings of filter tilt at retrieval in the clinical study. Goal Met. | |
| Filter Penetration | Low incidence, no clinical sequelae (asymptomatic). | 3 / 175 (1.7%) at placement, 2 / 88 (2.3%) at retrieval. Five total cases of asymptomatic penetration; none had clinical sequelae. Goal Met. | |
| New/Worsening DVT | Monitored, incidence reported. | New DVT: 10 / 137 (7.3%). Worsening DVT: 3 / 137 (2.2%). All new DVTs were in patients with active disease, hypercoagulable states, or orthopedic procedures. | |
| Delivery System Attributes | Various (Visibility, Trackability, Pushability, Deployment, Centering, Entanglement) | Acceptable performance as assessed by clinical evaluator (in animal study). | All assessed attributes (dilator visibility, marker band visibility, introducer sheath/marker band visibility, dilator/introducer trackability, dilator/introducer pushability, aspiration, delivery system trackability, delivery system pushability, ease of deployment, deployment accuracy, filter centering, arm/leg entanglement, filter visibility under fluoroscopy, snare tip visibility, and pusher assembly visibility) were found acceptable. Goal Met. |
| In-Vitro Tests | (Fatigue, Corrosion, Migration, Penetration, Tensile, Removal Force, Clot Trapping, Radiopacity, MRI Compatibility, Deployment Force/Accuracy, etc.) | Successful completion of testing as per risk assessment. | All acceptance criteria were met. Goal Met. |
| Biocompatibility | (Cytotoxicity, Sensitization, Irritation, Acute Systemic Toxicity, Subacute Toxicity, Genotoxicity, Hemocompatibility) | Compliant with ISO 10993. | All acceptance criteria were met. Goal Met. |
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
-
Clinical Study (Test Set):
- Sample Size: 175 patients (107 males, 68 females).
- Data Provenance: Prospective, multi-center clinical study conducted at 20 investigational sites across the United States.
-
Animal Studies (Test Set for In-Vivo Performance):
- Filter Assessment: 12 filter retrievals (ovine animal model).
- Delivery System Assessment: 12 Femoral and 12 Jugular/Subclavian DENALI® Filter Systems (acute ovine animal model).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
-
Clinical Study:
- Independent Clinical Events Committee (CEC): Responsible for adjudicating patient deaths, all site-reported adverse events, and abnormalities from venacavograms. Specific number of experts and their detailed qualifications (e.g., years of experience) are not explicitly provided, but they are described as an "independent Clinical Events Committee."
- Clinical Evaluators: Assessed "ease of removal" in the animal study and deemed various delivery system attributes acceptable. Qualifications are not further specified.
- Pathologist: Confirmed findings in the animal study (e.g., no caval occlusion/thrombosis) and determined the cause of a death. Qualifications are not further specified.
-
Animal Studies:
- Clinical Evaluator: Assessed ease of removal, delivery system attributes.
- Pathologist: Confirmed findings for cava wall damage, caval occlusion/thrombosis, etc.
- Attending Veterinarian: Determined the cause of a death in the animal study.
- Specific number and detailed qualifications of these individuals are not explicitly provided.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
-
Clinical Study: An Independent Clinical Events Committee (CEC) was used to adjudicate:
- Patient deaths.
- All site-reported adverse events.
- Abnormalities from venacavograms related to the device.
The specific method (e.g., 2+1, 3+1 for consensus) is not detailed, but the involvement of a committee implies a form of expert adjudication.
-
Animal Study: Adjudication involved clinical evaluators, a pathologist, and an attending veterinarian for various aspects. The specific method for dispute resolution or consensus is not detailed.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No MRMC comparative effectiveness study was done, and no AI component is mentioned. This submission is for a medical device (vena cava filter) and its associated delivery system, not an AI-based diagnostic or assistive software. Therefore, the questions related to human reader improvement with/without AI assistance are not applicable.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This submission is for a physical medical device (vena cava filter system), not an algorithm or AI.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- Clinical Study:
- Outcomes Data: Primary ground truth for clinical efficacy (CSP, TSP), recurrent PE, DVT, migration, fracture, tilt, and penetration were derived from patient follow-up visits, imaging (venacavograms), and clinical assessments.
- Expert Adjudication (CEC): Played a crucial role in establishing ground truth for adverse events, device-relatedness, and complex clinical outcomes.
- Animal Studies:
- Gross Evaluation and Histopathology: Used to assess cava wall damage, intimal irregularities, penetration, perforation, and thrombus.
- Venography: Used to assess cava wall damage.
- Clinical Evaluation: Used to assess ease of removal and various delivery system attributes.
8. The sample size for the training set
- Not explicitly mentioned as a distinct "training set" in the context of machine learning. For this physical device, the "training" equivalent would be the extensive in-vitro testing and prior experience with predicate devices that informed the DENALI® design.
- The "training" for the device's design and manufacturing processes would be based on years of experience and data from previous iterations like the ECLIPSE® Filter System.
- Performance testing is conducted on the final device to confirm its safety and efficacy, not to "train" an algorithm.
9. How the ground truth for the training set was established
- Not applicable in the AI/machine learning sense. The ground truth for the development of the physical device design (if one were to consider it "training") would be based on:
- Engineering principles and design specifications.
- Pre-clinical (in-vitro and animal) test results for predicate devices and earlier prototypes.
- Regulatory standards and guidance documents.
- Clinical experience and literature for the medical need and prior devices.
§ 870.3375 Cardiovascular intravascular filter.
(a)
Identification. A cardiovascular intravascular filter is an implant that is placed in the inferior vena cava for the purpose of preventing pulmonary thromboemboli (blood clots generated in the lower limbs and broken loose into the blood stream) from flowing into the right side of the heart and the pulmonary circulation.(b)
Classification. Class II. The special controls for this device are:(1) “Use of International Standards Organization's ISO 10993 ‘Biological Evaluation of Medical Devices Part I: Evaluation and Testing,’ ” and
(2) FDA's:
(i) “510(k) Sterility Review Guidance and Revision of 2/12/90 (K90-1)” and
(ii) “Guidance for Cardiovascular Intravascular Filter 510(k) Submissions.”