The NMPA granted innovation approvals to Inari Medical’s FlowTriever Retrieval/ Aspiration System and issued a review report.
The published review reports like this one serve as important references for you to understand what the regulatory authorities are thinking and evaluating during their review process. We have been following the list for the past several years and review the relevant ones for our clients’ specific products to gain more clarity and be more efficient in their submission and approval process. As NMPA standardizes and streamlines the review process for fast-track approval, domestic and overseas players can benefit from our expertise and experience.
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Product overview
- Product structure and composition
- Intended use
This product is intended for catheter-directed thrombectomy treatment in patients with acute high-risk pulmonary embolism (PE) or intermediate-risk PE with clinical deterioration, under one of the following conditions:
The presence of thrombus in the main pulmonary artery or major branches, with a high risk of bleeding or contraindications to thrombolytic therapy;
The presence of thrombus in the main pulmonary artery or major branches, and the patient has failed thrombolysis or aggressive medical therapy.
- Model/Specification
- Working principle
FlowTriever Thrombectomy Device: Utilizes a nitinol disk-based FlowTriever device to remove and capture thrombi.
Triever Aspiration Catheter: A large-bore aspiration syringe applies vacuum pressure inside the Triever aspiration catheter to extract thrombi.
FlowSaver Blood Return System: Used in conjunction with the Triever aspiration catheter to filter and recover aspirated thrombi and blood.
FlowStasis Adjustable Venous Hemostasis Device: Intended for temporarily maintaining suture tension after percutaneous venous procedures.
Large-Bore Aspiration Syringe: Used for generating negative pressure to facilitate aspiration.
Pre-clinical
1. Performance study
A series of bench tests were carried out on the FlowTriever thrombectomy device and Triever aspiration catheter to verify performance. These included evaluations of:
- Appearance and Dimensions: Devices were found to meet all specifications.
- Corrosion Resistance: All parts showed resistance to corrosion under test conditions.
- Mechanical Integrity: Tests of release force, retraction force, sealing, and compatibility with guidewires confirmed proper function.
- Component Compatibility: All components operated cohesively under simulated procedural conditions.
These results verified the devices conform to intended use requirements and safety standards.
2. Biocompatibility Studies
Biocompatibility was evaluated in accordance with ISO 10993 standards. Tests included:
- Cytotoxicity
- Sensitization
- Intracutaneous reactivity
- Systemic toxicity (acute and subacute)
- Genotoxicity
- Hemocompatibility
All test outcomes confirmed that the materials used in the FlowTriever system are biologically safe for clinical use.
3. Sterility and Shelf Life
Sterilization processes (ethylene oxide or gamma irradiation) were validated per ISO 11135 and ISO 11137 standards. Packaging integrity, shelf life, and bacterial endotoxin limits met the necessary requirements, with a confirmed shelf life of at least two years under accelerated aging conditions.
4. Animal Studies
Animal testing using acute and subacute embolic models (e.g., in porcine subjects) was conducted to evaluate the thrombectomy efficacy and potential vascular injury. Findings confirmed the ability to retrieve clots effectively from large pulmonary arteries without inducing vessel trauma or downstream embolism. Histopathological analysis showed no significant vessel wall damage.
Clinical Studies
Two major clinical studies supported the FlowTriever system’s efficacy and safety: the FLARE trial and the FLASH registry. Both studies addressed treatment of intermediate-risk or high-risk acute pulmonary embolism (PE) without using thrombolytics.
The FLARE Trial
The FLARE (FlowTriever Pulmonary Embolectomy Clinical Study) was a prospective, multicenter, single-arm trial designed to assess the clinical performance of the FlowTriever system in patients presenting with acute intermediate-risk pulmonary embolism. Conducted across 18 leading medical centers in the United States, the study initially aimed to enroll 103 participants and ultimately recruited 106. Of these, 101 were included in the Full Analysis Set (FAS), while 94 patients comprised the Per Protocol Set (PPS), ensuring robust data analysis.
Eligible participants were adults aged between 18 and 75 years, who had experienced PE symptoms for no more than 14 days. CT angiography confirmed the presence of a proximal embolism, and all patients exhibited a right ventricular to left ventricular (RV/LV) ratio of at least 0.9, a common marker of right heart strain. Hemodynamic stability was a prerequisite, with systolic blood pressure maintained at or above 90 mmHg—or at least 80 mmHg if successfully supported by fluids. A resting heart rate below 130 beats per minute further defined eligibility.
Patients were excluded if they had received thrombolytic therapy within the prior 30 days, suffered from active malignancy, or had contraindications to anticoagulant use.
The primary efficacy endpoint was the change in RV/LV ratio at 48 hours post-procedure, measured via computed tomography angiography. Investigators sought a clinically meaningful reduction of at least 0.12. The primary safety endpoint was the occurrence of major adverse events (MAEs) within 48 hours, which encompassed device-related deaths, major bleeding episodes, and significant procedural complications.
The results were striking. The average RV/LV ratio dropped from 1.55 at baseline to 1.13 within 48 hours after intervention—a highly statistically significant improvement (p < 0.0001). Importantly, the major adverse event rate was low, recorded at only 3.8%. These events were primarily associated with vascular access and not with the device itself. There were no incidences of device-related death or stroke throughout the study.
In conclusion, the FLARE study demonstrated that the FlowTriever system could offer substantial and rapid relief from right heart strain in patients with intermediate-risk PE. Its strong safety profile, achieved without the need for thrombolytic agents, underscored its potential as a safer alternative to traditional pharmacologic interventions.
The FLASH Registry
Following the success of FLARE, the FLASH (FlowTriever All-Comers Registry for Pulmonary Embolism) study was launched as a real-world, post-market registry to evaluate the broader safety and performance of the FlowTriever system. This prospective, multicenter, single-arm study enrolled a significantly larger cohort of patients, encompassing 800 individuals across 50 hospitals throughout the United States. Of these, 799 were ultimately included in the analysis, representing one of the most comprehensive real-world data collections on mechanical thrombectomy in PE treatment to date.
Participants in the FLASH registry represented a spectrum of PE severity, including both intermediate- and high-risk patients. All patients exhibited symptoms consistent with acute PE and had evidence of proximal emboli confirmed by either CT angiography or echocardiography. The inclusion criteria required participants to be 18 years or older, while exclusions applied to those with contraindications to anticoagulation, chronic thrombus formation, or anatomical barriers to catheter access.
Patients in this registry were divided into two main procedural groups: 695 patients were treated using the aspiration catheter alone, while 104 received both the thrombectomy stent and aspiration catheter. This allowed for a detailed evaluation of outcomes across different device configurations.
The primary safety endpoint of the study was the rate of major adverse events within 48 hours, which included device-related mortality, major bleeding, hemodynamic instability, respiratory decline, or pulmonary and cardiac injury associated with the device. Secondary safety measures included all-cause mortality at 30 days, serious device-related complications, and access-site issues. In parallel, several effectiveness endpoints were assessed, such as improvements in hemodynamic parameters—namely, cardiac index (CI), mean pulmonary artery pressure (MPAP), stroke volume index (SVI), and right ventricular stroke work index (RVSWI)—as well as changes in RV/LV ratio and clot burden reduction on imaging.
The findings from FLASH were both reassuring and impressive. The major adverse event rate was remarkably low at just 1.8% (14 out of 799 patients), with none of these events deemed directly related to the device. Mortality within 48 hours of treatment was 0%, and the 30-day mortality rate remained very low. Major bleeding was observed in only 1.4% of cases, again indicating a favorable safety profile, especially in comparison to thrombolytic-based strategies.
From an effectiveness standpoint, the device provided prompt and meaningful hemodynamic improvement. Among the 770 patients with available hemodynamic data, the mean pulmonary artery pressure decreased by 23.2 mmHg, while cardiac output, as reflected by the cardiac index, improved from 1.69 to 1.85 L/min/m². Stroke volume index increased by 9.56 mL/m² per beat, and total pulmonary vascular resistance (TPVR) declined significantly. The RV/LV ratio also showed consistent and sustained improvement: from a baseline value of 1.23, it fell to 0.98 within 48 hours, dropped further to 0.78 at 30 days, and remained favorable at 0.80 after six months.
A notable subgroup analysis focused on the FlowSaver blood reinfusion device, which was used in 81 patients. There were no adverse events related to reinfusion, such as infection or transfusion-related complications, underscoring the feasibility and safety of integrating this adjunct component.
Overall, the FLASH registry confirmed that the FlowTriever system could achieve rapid stabilization of cardiopulmonary function and sustain these improvements over time in a wide and diverse patient population. Its favorable safety profile, combined with the absence of thrombolytic drugs, further highlights its clinical value.
Overall Evaluation
From the comprehensive preclinical validations to robust clinical trial outcomes, the FlowTriever system has demonstrated:
- High safety margins with minimal MAEs
- Effective removal of pulmonary emboli
- Sustained cardiac and hemodynamic benefits
- Reduced need for thrombolytics, thereby minimizing bleeding risks
