(129 days)
ClearGuard HD Antimicrobial Barrier Cap is indicated for use with hemodialysis catheter hubs.
Using in vitro methods, the antimicrobial treatment on the ClearGuard HD Antimicrobial Barrier Cap has been shown to be effective at reducing microbial colonization in hemodialysis catheter hubs against the following microorganisms: Enterococcus faecium (VRE), Enterococus faecalis (VRE), Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus (MRSA), Staphylococcus aureus, Staphylococcus epidermidis (MRSE), Pseudomonas aeruginosa, Candida albicans and Candida parapsilosis and has not been shown to be effective against Candida paratropicalis and Klebsiella pneumoniae.
Using post-market clinical surveillance data, use of the ClearGuard HD Antimicrobial Barrier Cap has been shown to reduce the incidence of central-line associated bloodstream infections (CLABSI) in hemodialysis patients. Note: CLABSI was defined as a positive blood culture (PBC) not related to an alternative source of infection per the National Healthcare Safety Network (NHSN) surveillance definition. Alternative sources were excluded if dialysis sites attributed the PBC to vascular access on the dialysis event form. The actual reduction in CLABSI rates may be less substantial as the evaluation for alternative PBC sources was not pre-specified, nor standardized between pafients and clinical sites, and supplemental data evaluating for alternative sources were not available for review.
The subject device is not intended to be used for the treatment of existing infections. The antimicrobial is only present within the hub of the catheter and does not migrate to distal portions of the catheter.
The ClearGuard HD Antimicrobial Barrier Cap (hereinafter also referred to as the ClearGuard HD cap) is a single-use male luer lock cap that incorporates an antimicrobial treatment on its surfaces.
The ClearGuard HD cap consists of 1) a polypropylene polymer plug, which has a rod extending from the luer region that is coated with the antimicrobial agent chlorhexidine acetate (CHA) and 2) a nylon lock ring with threads that are also coated with CHA. When a ClearGuard HD cap is inserted into a liquid-filled catheter, CHA elutes from the rod into the catheter lock solution. This CHA solution is designed to kill microorganisms in the hemodialysis catheter hub, which results in a reduction in Central Line-Associated Bloodstream Infection (CLABSI) rates.
The catheter extension line pinch clamps are used to maintain the lock solution within the catheter lumens to minimize the risk of air embolism and maintain catheter patency. These clamps, which are closed when the catheter is not in use, mechanically confine the CHA and prevent diffusion of CHA toward the catheter tip and the patient's bloodstream.
The ClearGuard HD Antimicrobial Barrier Cap is designed to reduce microbial colonization in hemodialysis catheter hubs and, based on clinical surveillance data, to reduce the incidence of Central-Line Associated Bloodstream Infections (CLABSI) in hemodialysis patients.
Here's an analysis of the provided information:
1. Table of acceptance criteria and the reported device performance
| Acceptance Criteria / Performance Aspect | Reported Device Performance (ClearGuard HD) |
|---|---|
| Antimicrobial Effectiveness (In Vitro) | Shown to be effective at reducing microbial colonization in hemodialysis catheter hubs against: Enterococcus faecium (VRE), Enterococcus faecalis (VRE), Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus (MRSA), Staphylococcus aureus, Staphylococcus epidermidis (MRSE), Pseudomonas aeruginosa, Candida albicans, and Candida parapsilosis. Not shown to be effective against Candida paratropicalis and Klebsiella pneumoniae. These results were consistent "initially, and after 3 years real time shelf life." |
| Biocompatibility | Non-hemolytic, non-cytotoxic, non-irritating, non-sensitizing, non-mutagenic, non-toxic, and non-pyrogenic under intended use conditions. |
| Device Integrity | Met requirements for liquid leakage, disassembly torque, plug, shield and pouch integrity, and for antimicrobial quantity, elution, and solubility. |
| PBC Rate Reduction (Clinical) | ClearGuard HD: 0.28 per 1,000 CVC-days |
| Control (Tego+Curos): 0.75 per 1,000 CVC-days | |
| Incidence Rate Ratio (IRR): 0.37 | |
| Reduction in PBC Rate: 63% | |
| P-value: 0.001 (statistically significant reduction) | |
| CLABSI Rate Reduction (Clinical) | ClearGuard HD: 0.17 per 1,000 CVC-days |
| Control (Tego+Curos): 0.50 per 1,000 CVC-days | |
| Incidence Rate Ratio (IRR): 0.34 | |
| Reduction in CLABSI Rate: 66% (This was an exploratory ad-hoc analysis, not a pre-specified primary endpoint, and has limitations as noted in the document.) | |
| Safety | No device-associated adverse events reported during the clinical study or a previous study via the FDA's medical device reporting (MDR) system. |
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: For the clinical study, 1,671 subjects participated in the primary and exploratory analyses, accruing approximately 183,000 CVC-days in the primary analysis.
- ClearGuard HD Arm: 826 subjects
- Control Arm (Tego® Connector with Curos™ Disinfecting Cap): 845 subjects
- Data Provenance: The clinical study was a prospective, cluster-randomized, multi-arm, unblinded clinical study conducted at 40 dialysis facilities throughout the United States only.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the clinical study's test set. However, it notes that:
- "As is standard policy at the participating facilities, blood culture results were reported into the electronic health record in automated fashion and to the National Healthcare Safety Network (NHSN) Dialysis Event (DE) Form, from which they were abstracted for analysis."
- CLABSI was defined per the National Healthcare Safety Network (NHSN) surveillance definition.
- "All cultures were processed by a single clinical laboratory."
This suggests that the ground truth for PBCs and CLABSIs was established through standard clinical laboratory procedures and adherence to NHSN surveillance definitions, rather than through a panel of independent experts reviewing cases.
4. Adjudication method for the test set
The document does not describe a formal adjudication method (e.g., 2+1, 3+1) for the clinical study's test set. The determination of Positive Blood Cultures (PBCs) and CLABSIs appears to be based on laboratory results and the NHSN surveillance definition, with physicians at the dialysis sites making preliminary attributions of the PBC source on the Dialysis Event form.
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
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The device is an antimicrobial barrier cap, not an AI software intended for human interpretation improvement. The clinical study directly compared the effectiveness of two devices (ClearGuard HD vs. Tego+Curos) in reducing infection rates.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This question is not applicable as the ClearGuard HD Antimicrobial Barrier Cap is a physical medical device, not an algorithm or AI system.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- For antimicrobial effectiveness (in vitro tests): The ground truth was based on microbiological assays, specifically measuring reduction in microbial colonization.
- For biocompatibility: Ground truth was established through standardized biological evaluation tests (e.g., cytotoxicity, irritation, sensitization, toxicity, pyrogenicity).
- For clinical efficacy (PBC and CLABSI rates): The ground truth was based on outcomes data (positive blood cultures and CLABSI events) derived from patient medical records, laboratory results, and reported according to the National Healthcare Safety Network (NHSN) surveillance definition. Physicians at varying clinical sites attributed the PBC to a vascular access on the dialysis event form if no alternative source was identified. It is important to note the caveat regarding CLABSI: "The actual reduction in CLABSI rates may be less substantial as the evaluation for alternative PBC sources was not pre-specified, nor standardized between patients and clinical sites, and supplemental data evaluating for alternative sources were not available for review."
8. The sample size for the training set
This question is not applicable. The ClearGuard HD Antimicrobial Barrier Cap is a physical medical device and does not involve a "training set" in the context of machine learning or AI.
9. How the ground truth for the training set was established
This question is not applicable for the reasons stated above.
§ 876.5540 Blood access device and accessories.
(a)
Identification. A blood access device and accessories is a device intended to provide access to a patient's blood for hemodialysis or other chronic uses. When used in hemodialysis, it is part of an artificial kidney system for the treatment of patients with renal failure or toxemic conditions and provides access to a patient's blood for hemodialysis. The device includes implanted blood access devices, nonimplanted blood access devices, and accessories for both the implanted and nonimplanted blood access devices.(1) The implanted blood access device is a prescription device and consists of various flexible or rigid tubes, such as catheters, or cannulae, which are surgically implanted in appropriate blood vessels, may come through the skin, and are intended to remain in the body for 30 days or more. This generic type of device includes various catheters, shunts, and connectors specifically designed to provide access to blood. Examples include single and double lumen catheters with cuff(s), fully subcutaneous port-catheter systems, and A-V shunt cannulae (with vessel tips). The implanted blood access device may also contain coatings or additives which may provide additional functionality to the device.
(2) The nonimplanted blood access device consists of various flexible or rigid tubes, such as catheters, cannulae or hollow needles, which are inserted into appropriate blood vessels or a vascular graft prosthesis (§§ 870.3450 and 870.3460), and are intended to remain in the body for less than 30 days. This generic type of device includes fistula needles, the single needle dialysis set (coaxial flow needle), and the single needle dialysis set (alternating flow needle).
(3) Accessories common to either type include the shunt adaptor, cannula clamp, shunt connector, shunt stabilizer, vessel dilator, disconnect forceps, shunt guard, crimp plier, tube plier, crimp ring, joint ring, fistula adaptor, and declotting tray (including contents).
(b)
Classification. (1) Class II (special controls) for the implanted blood access device. The special controls for this device are:(i) Components of the device that come into human contact must be demonstrated to be biocompatible. Material names and specific designation numbers must be provided.
(ii) Performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(A) Pressure versus flow rates for both arterial and venous lumens, from the minimum flow rate to the maximum flow rate in 100 milliliter per minute increments, must be established. The fluid and its viscosity used during testing must be stated.
(B) Recirculation rates for both forward and reverse flow configurations must be established, along with the protocol used to perform the assay, which must be provided.
(C) Priming volumes must be established.
(D) Tensile testing of joints and materials must be conducted. The minimum acceptance criteria must be adequate for its intended use.
(E) Air leakage testing and liquid leakage testing must be conducted.
(F) Testing of the repeated clamping of the extensions of the catheter that simulates use over the life of the device must be conducted, and retested for leakage.
(G) Mechanical hemolysis testing must be conducted for new or altered device designs that affect the blood flow pattern.
(H) Chemical tolerance of the device to repeated exposure to commonly used disinfection agents must be established.
(iii) Performance data must demonstrate the sterility of the device.
(iv) Performance data must support the shelf life of the device for continued sterility, package integrity, and functionality over the requested shelf life that must include tensile, repeated clamping, and leakage testing.
(v) Labeling of implanted blood access devices for hemodialysis must include the following:
(A) Labeling must provide arterial and venous pressure versus flow rates, either in tabular or graphical format. The fluid and its viscosity used during testing must be stated.
(B) Labeling must specify the forward and reverse recirculation rates.
(C) Labeling must provide the arterial and venous priming volumes.
(D) Labeling must specify an expiration date.
(E) Labeling must identify any disinfecting agents that cannot be used to clean any components of the device.
(F) Any contraindicated disinfecting agents due to material incompatibility must be identified by printing a warning on the catheter. Alternatively, contraindicated disinfecting agents must be identified by a label affixed to the patient's medical record and with written instructions provided directly to the patient.
(G) Labeling must include a patient implant card.
(H) The labeling must contain comprehensive instructions for the following:
(
1 ) Preparation and insertion of the device, including recommended site of insertion, method of insertion, and a reference on the proper location for tip placement;(
2 ) Proper care and maintenance of the device and device exit site;(
3 ) Removal of the device;(
4 ) Anticoagulation;(
5 ) Management of obstruction and thrombus formation; and(
6 ) Qualifications for clinical providers performing the insertion, maintenance, and removal of the devices.(vi) In addition to Special Controls in paragraphs (b)(1)(i) through (v) of this section, implanted blood access devices that include subcutaneous ports must include the following:
(A) Labeling must include the recommended type of needle for access as well as detailed instructions for care and maintenance of the port, subcutaneous pocket, and skin overlying the port.
(B) Performance testing must include results on repeated use of the ports that simulates use over the intended life of the device.
(C) Clinical performance testing must demonstrate safe and effective use and capture any adverse events observed during clinical use.
(vii) In addition to Special Controls in paragraphs (b)(1)(i) through (v) of this section, implanted blood access devices with coatings or additives must include the following:
(A) A description and material characterization of the coating or additive material, the purpose of the coating or additive, duration of effectiveness, and how and where the coating is applied.
(B) An identification in the labeling of any coatings or additives and a summary of the results of performance testing for any coating or material with special characteristics, such as decreased thrombus formation or antimicrobial properties.
(C) A Warning Statement in the labeling for potential allergic reactions including anaphylaxis if the coating or additive contains known allergens.
(D) Performance data must demonstrate efficacy of the coating or additive and the duration of effectiveness.
(viii) The following must be included for A-V shunt cannulae (with vessel tips):
(A) The device must comply with Special Controls in paragraphs (b)(1)(i) through (v) of this section with the exception of paragraphs (b)(1)(ii)(B), (b)(1)(ii)(C), (b)(1)(v)(B), and (b)(1)(v)(C), which do not apply.
(B) Labeling must include Warning Statements to address the potential for vascular access steal syndrome, arterial stenosis, arterial thrombosis, and hemorrhage including exsanguination given that the device accesses the arterial circulation.
(C) Clinical performance testing must demonstrate safe and effective use and capture any adverse events observed during clinical use.
(2) Class II (performance standards) for the nonimplanted blood access device.
(3) Class II (performance standards) for accessories for both the implanted and the nonimplanted blood access devices not listed in paragraph (b)(4) of this section.
(4) Class I for the cannula clamp, disconnect forceps, crimp plier, tube plier, crimp ring, and joint ring, accessories for both the implanted and nonimplanted blood access device. The devices subject to this paragraph (b)(4) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.