The NovaCross CTO Microcatheter is intended to facilitate the intraluminal placement of conventional and steerable guidewires beyond the stenotic lesions, including chronic total occlusions (CTOs), and prior to PTCA or stent intervention. It is also intended to be used in conjunction with a steerable guidewire to access discrete regions of the coronary and peripheral vasculature and for guidewire exchange.

Device Description

The NovaCross™ CTO Microcatheter is a sterile, single-use, single lumen, over-the-wire, disposable percutaneous support catheter designed to facilitate the intraluminal placement of conventional and steerable guidewires beyond stenotic lesions (including chronic total occlusions) prior to PTCA or stent intervention and to be used in conjunction with a steerable guidewire to access discrete regions of the coronary and peripheral vasculature. The NovaCross™ CTO Microcatheter consists of stainless steel shaft, Over Tube, and a proximal Handle Body that allows for manual device manipulation and a means for flushing the catheter lumen. A key element of the device is a temporarily deployable and collapsible distal Nitinol Scaffold, which is visible through fluoroscopy when deployed by the user, and expands to the width of the artery to provide an anchoring to aid the user in establishing greater support near the treatment site.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the NovaCross™ CTO Microcatheter, based on the provided FDA 510(k) submission:

1. Table of Acceptance Criteria and Reported Device Performance

Category	Acceptance Criteria	Reported Device Performance
Primary Safety Endpoint (MI Rate)	Implied: MACE rate observed in the combined analysis of cohort A and B should be within an acceptable range, with an upper 97.5% confidence interval below a specific threshold (not explicitly stated, but derived from the p-value against some null hypothesis).	12.3% for the ITT population, with an upper 97.5% CI of 19.41%
Primary Effectiveness Endpoint (Technical Success)	Implied: Technical success rate should be above a predefined threshold (not explicitly stated, but derived from the reported 75.3% success rate meeting the endpoint).	75.3% for the ITT population (140/186)

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: 186 subjects across two cohorts (Cohort A: 145, Cohort B: 41).
Data Provenance: Not explicitly stated, but the submission mentions "10 investigational sites," implying the study was conducted at various clinical locations. The document refers to the submitter's location as Israel, and the regulatory consultant in the US, but the study locations are not detailed. It is a prospective study as it's an "IDE Clinical Study" and a "pivotal study" conducted to assess safety and efficacy.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the document. The study involved subjects undergoing Percutaneous Cardiac Intervention (PCI) for CTO, and the endpoints were clinical outcomes (MI rate, technical success). The determination of these outcomes would have been based on standard clinical practices, lab results (CK-MB), and interventional cardiologist assessment, but the specific number and qualifications of "experts" for ground truth adjudication are not detailed.

4. Adjudication Method for the Test Set

This information is not explicitly detailed for the clinical endpoints. Clinical trial data typically involves a Clinical Events Committee (CEC) for endpoint adjudication, but the specific method (e.g., 2+1, 3+1) is not mentioned in this summary.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The study described is a single-arm clinical trial assessing the device's safety and effectiveness, not comparing human readers with and without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This device is a physical medical device (microcatheter) and not an AI algorithm. Therefore, the concept of a "standalone" algorithm performance study is not applicable here. The study assesses the performance of the device in a clinical setting with human operators.

7. The Type of Ground Truth Used

For the primary safety endpoint (MI rate): Outcomes data based on clinical events and objective biomarker measurement (CK-MB > 3X ULN) and urgent revascularization.
For the primary effectiveness endpoint (technical success): Expert assessment/outcomes data based on the ability to successfully facilitate guidewire placement beyond the CTO in the true vessel lumen, as determined by the interventional cardiologists performing the procedure.

8. The Sample Size for the Training Set

This information is not applicable as the NovaCross™ CTO Microcatheter is a physical medical device and not an AI/machine learning algorithm that requires a training set. The "training" for this device would refer to its design, engineering tolerances, and preclinical testing.

9. How the Ground Truth for the Training Set Was Established

This information is not applicable for the same reason as above. The "ground truth" for the device's development and preclinical validation would involve engineering specifications, material properties, and various bench testing results (e.g., dimensional, torque response, tensile strength, scaffold durability) against predefined design criteria.

Summary

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April 2, 2020

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and then the word "ADMINISTRATION" in a smaller font size below.

Nitiloop Ltd. % Wanda Carpinella VP Regulatory Affairs Boston Biomedical Associates, LLC One Crowley Drive, Suite 216 Marlborough, Massachusetts 01752

Re: K193322

Trade/Device Name: NovaCross CTO Microcatheter Regulation Number: 21 CFR 870.1250 Regulation Name: Percutaneous Catheter Regulatory Class: Class II Product Code: DQY Dated: March 3, 2020 Received: March 4, 2020

Dear Wanda Carpinella:

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

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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-regulatory-assistance/contact-usdivision-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,

for Lydia Glaw Assistant Director DHT2C: Division of Coronary and Peripheral Intervention Devices OHT2: Office of Cardiovascular Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K193322

Device Name NovaCross CTO Microcatheter

Indications for Use (Describe)

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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Traditional Premarket Notification Submission - 510(k) NovaCross™ CTO Microcatheter 510(k) Number K193322

Date Prepared: April 1, 2020

I. SUBMITTER

Nitiloop Ltd. 1 Tidhar Street P.O Box 1040, Pardes Hana 3711001 Israel Tel: +972-(0)4- 9874202

Contact Person

Wanda Carpinella Company Regulatory Consultant Boston Biomedical Associates 100 Crowley Drive, Suite 216 Marlborough MA 01752 Cell: +1(781) 799-4572 wcarpinella@boston-biomedical.com

Back-up Company Contact:

Orly Maor 25 Sirkin Street Kfar Saba 44421 Israel Tel: +972-9-7453607 oram.ma@gmail.com

II. DEVICE

Name of Device: NovaCross™ CTO Microcatheter Common or Usual Name: NovaCross™ CTO Microcatheter Classification Name: Percutaneous catheter (21 CFR 870.1250) Regulatory Class: II Product Code: DOY

PREDICATE DEVICE III.

Nitiloop Ltd. believes that the NovaCross™ CTO microcatheter, which is the subject of this notification, is substantially equivalent to the following predicate device:

Boston Scientific; BridgePoint Medical system cleared under K102725
ASAHI® Cosair and Cosair Pro Microcatheter cleared under K171933

In addition, the following reference device is used:

. Nitiloop Ltd. NovaCross™ Microcatheter cleared under K143608 and K160389.

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IV. DEVICE DESCRIPTION

Subsequent to conventional guidewire placement, therapeutic devices such as atherectomy devices, PTCA catheters, and/or stents may be used to provide therapeutic benefit. The NovaCross™ CTO Microcatheter by itself does not provide therapeutic benefit beyond simple facilitation of guidewire support. The NovaCross™ CTO Microcatheter is similar in its design and it achieves its intended use by means of the same mechanisms as the predicate devices.

V. INDICATIONS FOR USE

The NovaCross™ CTO Microcatheter device is intended to facilitate the intraluminal placement of conventional and steerable guidewires beyond stenotic lesions, including chronic total occlusions (CTO), prior to PTCA or stent intervention. It is also intended to be used in conjunction with a steerable guidewire to access discrete regions of the coronary and peripheral vasculature and for guidewire exchange.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE VI. PREDICATE DEVICE AND REFERENCE DEVICE

The NovaCross™ CTO and the BridgePoint medical system and the ASAHI® Cosair / Cosair Pro Microcatheter have the same intended use. The NovaCross™ CTO and the BridgePoint Medical (the CrossBoss element), are both manufactured with stainless steel shafts with a lumen which is compatible for 0.014 guidwires. Also, both have stabilization systems - the BridgePoint system has an inflated balloon (Stingray) and the NovaCross™ CTO uses a nitinol scaffold. The ASAHI Corsair / Corsair Pro Microcatheters are also composed of a stainless steel shaft that supports placement of the guidewire beyond the chronic total occlusion.

The reference device, the cleared NovaCross™ MicroCatheter, and the NovaCross™ CTO have the same operating principles. Both use a Nitinol element (the superelasticity of the Nitinol is used), as the material to provide support to the guidewire and both include the same delivery system although the NovaCross™ CTO includes minor design modifications compared to the NovaCross™ device.

Questions related to clinical performance have been evaluated for the NovaCross™ CTO Microcatheter through extensive design verification and validation testing. including an IDE Clinical Study.

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VII. PERFORMANCE DATA

The following performance data were provided in support of the substantial equivalence determination:

Biocompatibility testing

An evaluation of biocompatibility for the NovaCross™ CTO microcatheter was conducted in accordance with FDA guidance, Use of International Standard ISO 10993-1. Testing included cytotoxicity, sensitization, intracutaneous study, pyrogenicity, SC5b-9 complement activation assay and hemolysis. All materials and processes of the NovaCross™ CTO device were shown to be biocompatible.

Sterilization, Packaging and Shelf Life Testing

The NovaCross™ CTO Microcatheter will be sterilized by EO gas. The sterilization cycle has been validated in compliance with ISO 11135:2014. In addition, shelf life and packaging testing were performed to support the labeled shelf life. All tests were successfully completed.

Mechanical Testing

Mechanical bench testing that has been performed on the NovaCross™ Microcatheter included the following:

Dimensional .
Simulated use ●
. Tip flexibility
. Torque response
Tensile strength .
. Fluid leak
Air leakage into hub assembly during aspiration ●
Pushability and retractability
. Scaffold durability

All tests met the predefined acceptance criteria and demonstrate substantial equivalence to the predicate NovaCross device and support a one year shelf life for the NovaCross™ Microcatheter.

Particulate and lubricity and corrosion testing were leveraged from the predicate NovaCross™ Microcatheter.

VIII. CLINICAL DATA

A multicenter, non-randomized, open label, single arm pivotal study was conducted to assess the safety and efficacy of the NovaCross™ CTO Microcatheter device in subjects undergoing Percutaneous Cardiac Intervention for Chronic Total Occlusion. The study was performed in two cohorts, and included 186 subjects that were recruited in 10 investigational sites.

Primary Safety Endpoint

The primary safety endpoint of the study was the rate of post-procedure MI rate, defined as > X3 upper normal limit of CK-MB cardiac biomarker. the overall MACE rate observed in the combined analysis of cohort A and cohort B was 12.3% for the ITT population, with an upper confidence interval of 19.41% (97.5% Cl). The following tables summarize the MACE rate according to each definition and for the ITT population for both device- related and not related events.

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Category	Statistics	Cohort A(N=145)	Cohort B(N=41)	Cohort A + B(N=186)	97.5% Upper CI1	P-Value1
MACE	% (n/N)	14.0% (16/114)	7.3% (3/41)	12.3% (19/155)	19.41%	0.0020
Death	N	0	0	0
Protocol definition of MI	N	16	3	19
Urgent revascularization	N	0	0	0

MACE events composite for ITT population

MACE defined as the composite of death, protocol definition of MI (CK-MB>3X ULN), or urgent revascularization (target vessel revascularization (TVR) or urgent coronary artery bypass surgery (CABG)).

Primary Effectiveness Analysis

Primary effectiveness endpoint was set as a technical success, which was defined as the ability of the NovaCross™ CTO Microcatheter to successfully facilitate placement of a guidewire beyond a native coronary chronic total occlusion (CTO) in the true vessel lumen. The results of the study showed a technical success of 75.3%.

Summary of Primary Effectiveness Endpoint for ITT Population:

Category	Statistics	Cohort A(N=145)	Cohort B(N=41)	Cohort A + B(N=186)
Technical success	% (n/N)	75.9% (110/145)	73.2% (30/41)	75.3% (140/186)

The results of this pivotal study show that the device has met both the primary safety endpoint and the primary effectiveness endpoint. It also met the secondary endpoints, associated with both the effectiveness and safety of the device. It was therefore concluded that the device is safe, effective and easily used and handled by interventional cardiologists.

IX. CONCLUSIONS

The NovaCross™ CTO Microcatheter was determined to be substantially equivalent to the predicate device.

Regulation Number and Section

§ 870.1250 Percutaneous catheter.

(a)
Identification. A percutaneous catheter is a device that is introduced into a vein or artery through the skin using a dilator and a sheath (introducer) or guide wire.(b)
Classification. Class II (performance standards).