(291 days)
The Cool Line Catheter Model CL-2295A when used with the ZOLL Thermal Regulation System is indicated for use in fever reduction, as an adjunct to antipyretic therapy, in adult patients with cerebral infarction and intracerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated.
The ZOLL ICY Intravascular Heat Exchange Catheter Model IC-3893-A, connected to the ZOLL CoolCard 3000/ Thermogard XP Thermal Regulation System, is indicated for use:
- · In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
- · To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.
The ZOLL Quattro Catheter Model IC-4593, connected to a ZOLL Thermal Regulation System, is indicated for use:
- · In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
- · To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.
The Start-Up Kit (SUK) is intended to control patient core temperature using heat exchange fluid in conjunction with CoolGard 3000 or Thermogard XP system and ZOLL Heat Exchange Catheters, but does not have a specific independent indications for use.
The ZOLL Intravascular Heat Exchange Catheters (Cool Line, ICY, and Quattro - ZOLL Catheters) are sterile, single use heparin coated flexible catheters designed for placement in the femoral, jugular, or subclavian veins. The Cool Line Catheter contains two heat exchange balloons, the ICY Catheter contains three heat exchange balloons, and the Quattro Catheter contains four heat exchange balloons.
The ZOLL Catheters are connected to a single use, disposable Start-Up Kit (SUK) and the CoolGard 3000® or Thermogard XP® Console. The catheters connect to the console coolant well via tubing integral to the SUK. The catheter is connected to the SUK by connecting the male outflow Luer of the SUK to the female inflow Luer of the catheter and the female inflow Luer of the SUK to the male outflow Luer of the catheter. Both SUK Luers, in turn, are connected via tubing to a heat exchange coil through which saline circulates. The coil is placed in a coolant well located in the console. The controlled temperature saline is circulated through the closed-loop circuit of the SUK and catheter using the console pump, after which the saline is then returned within the SUK to the console heater and chiller coolant well via the catheter's outflow lumen.
The Catheters. SUK and the CoolGard 3000 or Thermogard XP Console are supplied separately. The ZOLL Intravascular Heat Exchange System is also designed for use with an off-the-shelf temperature probe, which is supplied separately and not manufactured by ZOLL.
This document is a 510(k) premarket notification for a medical device (ZOLL Intravascular Heat Exchange Catheters and Start-Up Kit). It primarily focuses on demonstrating substantial equivalence to previously cleared predicate devices after minor modifications (specifically, changes to Luer designs and materials, and the addition of a deflation syringe to the SUK).
The FDA's review letter (pages 1-3) does mention a historical randomized controlled trial (RCT) for the Cool Line Intravascular Heat Exchange Catheter to support a specific warning label regarding its use for fever reduction in certain patient populations. However, this study was not conducted specifically to validate the modified devices described in this 510(k) submission, but rather to establish safety and effectiveness of the original Cool Line Catheter's indications for use. The current 510(k) submission states that "Clinical evaluations were not performed for the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters because such evaluations were not necessary to demonstrate substantial equivalence of the modified devices to the predicate devices."
Therefore, for the current submission's modified devices, there is no acceptance criteria or study that proves the modified device meets new such criteria, as the submission claims substantial equivalence to predicate devices based on non-clinical testing. The provided tables are for non-clinical performance tests (packaging, bench performance, biocompatibility, usability) to ensure the modifications do not negatively impact the device's original performance.
However, since the initial request asks for acceptance criteria and a study that proves the device (referring to the Cool Line Catheter in general, based on the warning label content) meets acceptance criteria, I will address the randomized controlled trial mentioned in the FDA letter for the Cool Line Intravascular Heat Exchange Catheter's general performance as it relates to the specified warning.
Acceptance Criteria and Study for the Cool Line Intravascular Heat Exchange Catheter (as presented in the FDA warning and 510(k) summary)
It's important to clarify that the provided document outlines the process for demonstrating substantial equivalence of modified devices (Cool Line Intravascular Heat Exchange Catheter, ICY Intravascular Heat Exchange Catheter, Quattro Intravascular Heat Exchange Catheter, Start-Up Kit) to their predicate versions. The extensive details about "acceptance criteria" and "study results" within the 510(k) application itself (like in Tables 3-7) refer to non-clinical tests (packaging, bench performance, biocompatibility, and usability/human factors) conducted to confirm that the modifications do not adversely affect the device's established safety and effectiveness.
The only "study" mentioned that relates to clinical effectiveness for the Cool Line Catheter is a randomized controlled trial (RCT), which is cited to support a Warning label on the device regarding specific patient populations. This RCT examined the safety and effectiveness of the Cool Line Catheter for fever reduction, but the results led to a limitation on its indications for use rather than specific "acceptance criteria" being met for those populations. The effectiveness of the device for fever reduction in Cerebral Infarction (CI) and Intracerebral Hemorrhage (ICH) patients is implied by its indication for use in these groups, but the detailed acceptance criteria for this specific clinical efficacy are not provided in this document. Instead, the document provides mortality data from a historical trial.
1. A table of acceptance criteria and the reported device performance
For the Cool Line Intravascular Heat Exchange Catheter as it relates to the FDA's warning:
| Acceptance Criteria Category | Specific Criteria (Implicit from FDA Warning) | Reported Device Performance (Mortality Rates from RCT) |
|---|---|---|
| Clinical Effectiveness | No demonstrated safety for fever reduction in patients with subarachnoid hemorrhage (SAH) or primary traumatic brain injury (PTBI), specifically concerning mortality. | Cool Line Group:CI: 18.8% (3/16)ICH: 24.2% (8/33)PTBI: 22.7% (10/44)SAH: 21.3% (13/61)Control Group:CI: 21.4% (3/14)ICH: 25.9% (7/27)PTBI: 10.5% (4/38)SAH: 11.1% (7/63) |
| Statistical Significance | P-value for mortality differences between Cool Line and Control groups should ideally show non-inferiority or superiority for indicated uses, and lack thereof for non-indicated uses. | P-values (Fischer's exact test):CI: 0.74ICH: 1.00PTBI: 0.24SAH: 0.15(Note: P-values > 0.05 generally indicate no statistically significant difference, which in this context means the Cool Line did not show a statistically significant benefit in mortality compared to standard care for any of the tested populations, and for PTBI and SAH, mortality was numerically higher, leading to the warning.) |
For the modified devices in this 510(k) submission, the "acceptance criteria" are product design specifications met through non-clinical testing. Examples include:
| Acceptance Criteria Category | Specific Criteria (Example from Non-Clinical Tests) | Reported Device Performance (Example from Non-Clinical Tests) |
|---|---|---|
| Packaging Validation (SUK) | All package seals and tray seals are undamaged. | All package seals and tray seals were undamaged (Table 3). |
| Bench Performance (SUK) | No leaks below specified acceptance criteria during high pressure leak test. | No leaks were noted below the specified pressure (Table 4). |
| Bench Performance (Catheter) | All Luers meet requirements after alcohol resistance test (no crazing/cracking). | No Luers showed evidence of crazing or cracking after being soaked in alcohol (Table 5). |
| Biocompatibility | No cytotoxicity (reactivity grade "0"). | Reactivity grade of all test article extract samples was "0" (Table 7). |
| Biocompatibility | No sensitization reactions caused by test article extracts. | The test article extracts did not cause sensitization reactions under the conditions of the assay (Table 7). |
| Usability/Human Factors (Summative) | 100% of users pass critical tests regarding device connection and saline aspiration. | All participants passed critical tests (100% successful completion rate) (page 16). |
Regarding the Randomized Controlled Trial for the Cool Line Catheter (cited for the warning):
2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size: 296 patients
- Data Provenance: The document does not specify the country of origin of the data. It was a prospective randomized controlled trial.
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)
- This information is not provided in the document. The trial focused on mortality outcomes, which are typically objectively measured without expert consensus on diagnostic classifications for the "ground truth" of the test set itself, though diagnoses for patient inclusion (CI, ICH, PTBI, SAH) would have been established clinically by treating physicians.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- This information is not provided in the document.
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, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted, nor is the device an AI device. This study was a clinical trial comparing patient outcomes (mortality) between a device treatment arm and a control arm, not an imaging interpretation study.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- No, this device is a physical catheter for thermal regulation, not an algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
- The ground truth in the randomized controlled trial was outcomes data, specifically mortality. Patient diagnoses (CI, ICH, PTBI, SAH) were also used for stratification and analysis.
8. The sample size for the training set
- Since this was a randomized controlled trial for clinical outcomes, it does not have a "training set" in the context of machine learning or AI. The 296 patients constituted the study population for evaluating the device's effects.
9. How the ground truth for the training set was established
- Not applicable, as there was no "training set" in the machine learning sense. Clinical diagnoses for patient enrollment and the objective outcome of mortality were used.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 30, 2015
ZOLL Circulation, Inc. Mr. Sam Nanavati V.P., Quality Assurance and Regulatory Affairs 2000 Ringwood Avenue San Jose, California 95131
Re: K150046
Trade/Device Name: Cool Line Intravascular Heat Exchange Catheter, ICY Intravascular Heat Exchange Catheter, Quattro Intravascular Heat Exchange Catheter, Start-Up Kit (SUK) Regulation Number: 21 CFR 870.5900 Regulation Name: Thermal Regulating System Regulatory Class: Class II Product Code: NCX Dated: September 30, 2015
Received: October 2, 2015
Dear Mr. Sam Nanavati:
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 and the limitations described below. 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.
The Office of Device Evaluation has determined that there is a reasonable likelihood that the Cool Line Intravascular Heat Exchange Catheter will be used for an intended use not identified in the proposed labeling and that such use could cause harm. Therefore, in accordance with Section 513(i)(1)(E) of the Act, the following limitation must appear in the Warnings section of the device's labeling as a box warning immediately following the indications for use statement:
The safety of this device has not been demonstrated for fever reduction in patients presenting with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled,
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are presented in the table below (CI - cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH - subarachnoid hemorrhage).
| Cool Line | Control | ||||||
|---|---|---|---|---|---|---|---|
| n | N | % | n | N | % | p* | |
| CI | 3 | 16 | 18.8 | 3 | 14 | 21.4 | 0.74 |
| ICH | 8 | 33 | 24.2 | 7 | 27 | 25.9 | 1.00 |
| PTBI | 10 | 44 | 22.7 | 4 | 38 | 10.5 | 0.24 |
| SAH | 13 | 61 | 21.3 | 7 | 63 | 11.1 | 0.15 |
| Mortality by Diagnosis (ITT analysis) | ||||
|---|---|---|---|---|
| --------------------------------------- | -- | -- | -- | -- |
*Fischer's exact test
For more details on the clinical trial results please refer to Physician's Manual - "Normothermia for the Neuro-critically Ill stroke patient" PN 8700-0634-01.
Please note that the above labeling limitation is required by Section 513(i)(1)(E) of the Act. Therefore, a new 510(k) is required before these limitations are modified in any way or removed from the device's labeling. This limitation does not apply to the ICY and Quattro Intravascular Heat Exchange Catheters.
The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and permits your device to proceed to the market. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification if the limitation statement described above is added to your labeling.
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 (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part
{2}------------------------------------------------
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.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Jonette R. Foy -S
William H. Maisel, MD, MPH Director (Acting) Office of Device Evaluation Deputy Center Director for Science Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K150046
Device Name
Cool Line Intravascular Heat Exchange Catheter, ICY Intravascular Heat Exchange Catheter, Quattro Intravascular Heat Exchange Catheter, Start-Up Kit (SUK)
Indications for Use (Describe)
The Cool Line Catheter Model CL-2295A when used with the ZOLL Thermal Regulation System is indicated for use in fever reduction, as an adjunct to antipyretic therapy, in adult patients with cerebral infarction and intracerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated.
WARNING - Fever Reduction
The safety of this device has not been demonstrated for fever reduction with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled, are presented in the table below (CI - cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH subarachnoid hemorrhage).
| Mortality by Diagnosis (ITT analysis). |
|---|
| -------------------------------------------- |
| Cool Line | |||||||
|---|---|---|---|---|---|---|---|
| n | N | % | n | N | % | p* | |
| CI | 3 | 16 | 18.8 | 3 | 14 | 21.4 | 0.74 |
| ICH | 8 | 33 | 24.2 | 7 | 27 | 25.9 | 1.00 |
| PTBI | 10 | 44 | 22.7 | র্ব | 38 | 10.5 | 0.24 |
| SAH | 13 | 61 | 21.3 | 7 | 63 | 11.1 | 0.15 |
*Fischer's exact test
For more details on the clinical trial results planial is Manual - "Normothermia for the Neuro-critically III stoke patient" PN 8700-0634-01.
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The ZOLL ICY Intravascular Heat Exchange Catheter Model IC-3893-A, connected to the ZOLL CoolCard 3000/ Thermogard XP Thermal Regulation System, is indicated for use:
- · In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
- · To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.
The ZOLL Quattro Catheter Model IC-4593, connected to a ZOLL Thermal Regulation System, is indicated for use:
- · In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
- · To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.
The Start-Up Kit (SUK) is intended to control patient core temperature using heat exchange fluid in conjunction with CoolGard 3000 or Thermogard XP system and ZOLL Heat Exchange Catheters, but does not have a specific independent indications for use.
| 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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PREMARKET NOTIFICATION 510(K) SUMMARY
| Date Prepared: | September 25, 2015 |
|---|---|
| Submitter: | ZOLL Circulation, Inc. |
| Address: | 2000 Ringwood AvenueSan Jose, CA 95131 |
| Phone: | 408-419-2950 |
| Fax: | 408-541-1030 |
| Contact Person: | Sam Nanavati, VP, Quality and Regulatory Affairs |
| Trade Name/ProprietaryName: | Cool Line® Intravascular Heat Exchange CatheterICY® Intravascular Heat Exchange CatheterQuattro™ Intravascular Heat Exchange CatheterStart-Up Kit (SUK) |
| Common Name: | Central Venous Catheter (short term) and Thermal RegulatingSystem |
| Classification/Name: | Class II; System, Hypothermia, Intravenous, Cooling |
| Regulation: | 21 CFR 870.5900, Thermal Regulating System |
| Product Code: | NCX |
| Legally marketed devices towhich substantialequivalence is claimed: | Cool Line Catheter Kit Model CL-2295A (K101987); ICYCatheter Kit Model IC-3893A (K101987); Quattro Catheter KitModel IC-4593 (K101987); Start-Up Kit Model CG-500D andModel CG-500D EX (K014241) |
I. Device Description
The ZOLL Intravascular Heat Exchange Catheters (Cool Line, ICY, and Quattro - ZOLL Catheters) are sterile, single use heparin coated flexible catheters designed for placement in the femoral, jugular, or subclavian veins. The Cool Line Catheter contains two heat exchange balloons, the ICY Catheter contains three heat exchange balloons, and the Quattro Catheter contains four heat exchange balloons.
The ZOLL Catheters are connected to a single use, disposable Start-Up Kit (SUK) and the CoolGard 3000® or Thermogard XP® Console. The catheters connect to the console coolant well via tubing integral to the SUK. The catheter is connected to the SUK by connecting the male outflow Luer of the SUK to the female inflow Luer of the catheter and the female inflow Luer of the SUK to the male outflow Luer of the catheter. Both SUK Luers, in turn, are connected via tubing to a heat exchange coil through which saline circulates. The coil is placed in a coolant well located in the console. The controlled temperature saline is circulated through the closed-loop circuit of the SUK and catheter using the console pump, after which the saline is then returned within the SUK to the console heater and chiller coolant well via the catheter's outflow lumen.
The Catheters. SUK and the CoolGard 3000 or Thermogard XP Console are supplied separately. The ZOLL Intravascular Heat Exchange System is also designed for use with an off-the-shelf temperature probe, which is supplied separately and not manufactured by ZOLL.
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II. Indications for Use
The intended use / indications for use of the modified Cool Line, ICY, and Quattro Catheters are identical to the intended use / indications for use of the predicate Cool Line, ICY, and Quattro Catheters [cleared by FDA on October 12, 2010 under 510(k) K101987], which is as follows:
Cool Line Intravascular Heat Exchange Catheter
The Cool Line Catheter Model CL-2295A when used with the ZOLL Thermal Regulation System is indicated for use in fever reduction, as an adjunct to antipyretic therapy, in adult patients with cerebral infarction and intracerebral hemorrhage who require access to the central venous circulation and who are intubated and sedated.
Warning - Fever Reduction
The safety of this device has not been demonstrated for fever reduction in patients presenting with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled, are presented in the table below (CI - cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH - subarachnoid hemorrhage).
| Cool Line | Control | ||||||
|---|---|---|---|---|---|---|---|
| n | N | % | n | N | % | p* | |
| CI | 3 | 16 | 18.8 | 3 | 14 | 21.4 | 0.74 |
| ICH | 8 | 33 | 24.2 | 7 | 27 | 25.9 | 1.00 |
| PTBI | 10 | 44 | 22.7 | 4 | 38 | 10.5 | 0.24 |
| SAH | 13 | 61 | 21.3 | 7 | 63 | 11.1 | 0.15 |
Mortality by Diagnosis (ITT analysis)
*Fischer's exact test
For more details on the clinical trial results please refer to Physician's Manual - "Normothermia for the Neuro-critically III stroke patient" PN 8700-0634-01.
ICY Intravascular Heat Exchange Catheter
The ZOLL ICY Intravascular Heat Exchange Catheter Model IC-3893-A, connected to the ZOLL CoolGard 3000/Thermogard XP Thermal Regulation System, is indicated for use:
- . In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
- . To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.
Quattro Intravascular Heat Exchange Catheter
The ZOLL Quattro Catheter Model IC-4593, connected to a ZOLL Thermal Regulation System, is indicated for use:
- . In cardiac surgery adult patients to achieve and/or maintain normothermia during surgery and recovery/intensive care, and
- . To induce, maintain and reverse mild hypothermia in neurosurgery adult patients in surgery and recovery/intensive care.
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The SUK is intended to control patient core temperature using heat exchange fluid in conjunction with CoolGard 3000 or Thermogard XP system and ZOLL Heat Exchange Catheters, but does not have a specific independent indications for use.
III. Technological Characteristics of the Device Compared to the Predicate Device
The modified SUK and the modified Cool Line. ICY, and Quattro Intravascular Heat Exchange Catheters are substantially equivalent to the 510(k) cleared Cool line, ICY and Quattro Catheters (SUK: K072234; Catheters: K101987), with regard to intended use / indications for use, technological characteristics, and principles of operation. Table 2 provide a comparison of the similarities and differences in technological characteristics between the modified SUK and Cool Line, ICY, and Quattro Catheters, to the cleared SUK and Cool Line, ICY, and Quattro Catheters.
| Characteristic | PREDICATE DEVICESZOLL Cool Line, ICY and QuattroCatheters with ZOLL Standard Luers | SUBJECT DEVICESZOLL Cool Line, ICY and QuattroCatheters with ZOLL Custom Luers(modified) |
|---|---|---|
| 510(k) Number | K101987 | K150046 |
| Class | II | Same |
| Classification/Regulation Name | System, Hypothermia, Intravenous,Cooling/Thermal Regulating System | Same |
| RegulationNumber | 21 CFR 870.5900 | Same |
| Product Code | NCX | Same |
| Insertion Site | Cool Line – femoral vein, jugular vein,subclavian veinICY – femoral veinQuattro – femoral vein | Same |
| Heparin Coating | SurModics Applause Heparin Coating | Same |
| Luer Designs | Inflow and Outflow Luers: ZOLL Standard LuersInfusion Luers: ZOLL Standard LuersVent Caps: ZOLL Standard Vent Caps | Inflow and Outflow Luers: ZOLL CustomLuersInfusion Luers: ZOLL Standard LuersVent Caps: ZOLL Custom Vent Caps |
| Luer Materials | Base material is polyurethane (for all luersexcept for vent caps)Inflow and outflow Luers: Polyurethane:TecoplastOP-770-321 Teal GreenDistal infusion Luer: Polyurethane:TecoplastOP-770-477 BrownMedial infusion Luer: Polyurethane:Tecoplast | SameInflow and outflow Luers: Polyurethane:TecoplastOP-770-164 OrangeDistal infusion Luer: Same as predicate(except pad printing has changed from blackink to white ink)Medial infusion Luer: Same as predicate |
| Characteristic | PREDICATE DEVICESZOLL Cool Line, ICY and QuattroCatheters with ZOLL Standard Luers | SUBJECT DEVICESZOLL Cool Line, ICY and QuattroCatheters with ZOLL Custom Luers(modified) |
| OP-770-White | ||
| Proximal infusion Luer: Polyurethane:TecoplastOP-770-541 Dark Blue | Proximal infusion Luer: Same as predicate(except pad printing has changed from blackink to white ink) | |
| Male vent cap: ABS: (purchasedcomponent)Merit Medical (P/N 101031001) | Male vent cap: ABS: Ineos Lustran (P/N 348-012002) | |
| Female vent cap: Polypropylene:(purchased component) Merit Medical(P/N 101030002) | Female vent cap: ABS: Ineos Lustran (P/N348-012002) | |
| Catheter workinglength (tip tomanifold) | Cool Line - 22 cmICY - 38 cmQuattro - 45 cm | Same |
| Shaft diameter | 9.3 Fr | Same |
| Number of lumens | 5 lumens: 2 infusion, 1 guidewire (plusinfusion), 1 inflow, 1 outflow | Same |
| GuidewireCompatibility | 0.032" | Same |
| Heat ExchangeBalloons | Cool Line - 2 (straight/ coaxial)ICY - 3 (straight/coaxial)Quattro - 4 (straight/coaxial) | Same |
| Flow Rate (bylumen) | Cool LineDistal - 2100 mL/hrMedial - 1200 mL/hrProximal - 1400 mL/hrICYDistal – 1700 mL/hrMedial - 900 mL/hrProximal - 1200 mL/hrQuattroDistal - 1300 mL/hr | Same |
| Medial - 800 mL/hrProximal - 1100 mL/hr | ||
| Approx. InflatedBalloon OD(Cross-sectionalArea) | Cool Line: ~5mm(20mm²)ICY and Quattro: ~8mm(50mm²) | Same |
| Heat ExchangePower | Cool Line - 65 Watts nominalICY - 140 Watts nominalQuattro - 190 Watts nominal | Same |
| Characteristic | PREDICATE DEVICESZOLL Cool Line, ICY and QuattroCatheters with ZOLL Standard Luers | SUBJECT DEVICESZOLL Cool Line, ICY and QuattroCatheters with ZOLL Custom Luers(modified) |
| Materials: | ||
| Shaft | Polyurethane | Same |
| Balloon | PET and Polyurethane (ICY and Quattro)Polyurethane (Cool Line) | Same |
| Sterilization | Ethylene Oxide (EO) | Same |
Table 1. Comparison of Proposed Modified Catheters with Predicates
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** The Indication for Use for the Cool Line Catheter also includes the following black box warning:
Warning - Fever Reduction
The safety of this device has not been demonstrated for fever reduction with subarachnoid hemorrhage or primary traumatic brain injury. The safety and effectiveness of this device was examined in a randomized controlled trial of 296 patients. The mortality results reported in this trial, for the four patient cohorts enrolled, are presented in the table below (CI cerebral infarction, ICH - intracerebral hemorrhage, PTBI - primary traumatic brain injury, SAH - subarachnoid hemorrhage).
| Mortality by Diagnosis (ITT analysis) | |||||||
|---|---|---|---|---|---|---|---|
| Cool Line | Control | ||||||
| n | N | % | n | N | % | p* | |
| CI | 3 | 16 | 18.8 | 3 | 14 | 21.4 | 0.74 |
| ICH | 8 | 33 | 24.2 | 7 | 27 | 25.9 | 1.00 |
| PTBI | 10 | 44 | 22.7 | 4 | 38 | 10.5 | 0.24 |
| SAH | 13 | 61 | 21.3 | 7 | 63 | 11.1 | 0.15 |
*Fischer's exact test
For more details on the clinical trial results please refer to Physician's Manual - "Normothermia for the Neuro-critically III stroke patient" PN 8700-0634-01.
Table 2. Comparison of Proposed Modified Start-Up Kit with Predicates
| Characteristic | PREDICATE DEVICESZOLL Start-Up Kit with ZOLLStandard Luers | SUBJECT DEVICESZOLL Start-Up Kit with ZOLL CustomLuers(modified) |
|---|---|---|
| 510(k) Number | K014241 | K150046 |
| Intended Use | To control patient core temperature usingheat exchange fluid in conjunction withCoolGard 3000 or Thermogard XPsystem and ZOLL Heat ExchangeCatheters | Same |
| Indications for Use | Start-Up Kit does not have a specificindependent indications for use | Same |
| Class | II | Same |
| Classification/Regulation Name | System, Hypothermia, Intravenous,Cooling/Thermal Regulating System | Same |
| Regulation Number | 21 CFR 870.5900 | Same |
| Product Code | NCX | Same |
| Patient Contact | Indirect patient contact | Same |
| Luer Function | Join the SUK to the InFlow/OutFlowLumens of the catheters, and allow salineto circulate through the catheter/SUKfluid path | Same |
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| Characteristic | PREDICATE DEVICESZOLL Start-Up Kit with ZOLLStandard Luers | SUBJECT DEVICESZOLL Start-Up Kit with ZOLL CustomLuers(modified) |
|---|---|---|
| Supplied 20 mlSterile Deflation(Slip-Fit) Syringe | Syringe not provided with SUK | Syringe, compatible with new custom Luerlocks, provided with SUK for optionalremoval of saline from catheter heat exchangeballoons prior to catheter removal |
| Luer Materials:SUK Female Luer(InFlow) | PVC: Alpha Gary 2212-RHT/1-118Clear | PVC:Alpha Gary 2212-RHT/1-118UN2243 Orange |
| SUK Male Luer(OutFlow) | Acrylic: 65117 | PVC:Alpha Gary 2212-RHT/1-118UN2243 Orange |
| Sterilization | Provided sterile (Gamma sterilization) | Same |
IV. Summary of the Nonclinical Tests Performed
Nonclinical testing was performed to ensure that the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters meet their predetermined design and performance specifications and that the product is substantially equivalent to the predicate devices (SUK: K014241; Catheters: K101987).
The modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters are identical to the 510(k) cleared SUK and 510(k) cleared Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters in terms of intended use/indications for use and principles of operation, and the modified devices have equivalent technological characteristics to the cleared devices. Nonclinical testing completed includes Packaging validation (SUK only), Bench Performance, Biocompatibility, and Usability Testing. The non-clinical test results demonstrate that the modified devices continue to meet product design specifications.
Bench Performance
Packaging Validation
Packaging performance testing of the modified SUK was performed to verify that following exposure to simulated shipping conditions, the addition of the sterile packaged 20 mL Deflation (Slip-Fit) syringe to the outside of the sterilized SUK packaging does not impact the integrity of the SUK sterile packaging. Packaging testing completed is shown in Table 3.
| Test Name | Test Method Summary | Results |
|---|---|---|
| Visual Inspection | Visual inspection to inspectshipping boxes and trays fordamage. | All shipping boxes and trays wereundamaged. |
| SUK Package Seal Visual Integrity | Visual inspection to inspect thepackage seal in the area where thesyringe bag is attached. | All package seals and tray sealswere undamaged. |
| Syringe Pouch Seal Visual Integrity& Adhesion to Tyvek | Visual inspection of the affectedarea to inspect the package seal area | All syringe pouch seals and the filmand Tyvek portion of the poucheswere undamaged. |
Table 3. Start-Up Kit Packaging Testing
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| Test Name | Test Method Summary | Results |
|---|---|---|
| of the syringe bag and film andTyvek portion of the pouch. | ||
| SUK Package Seal Peel Test | Peel testing of the affected area toensure that seal peel data is not lessthan specified acceptance criteria | All SUK package seals wereundamaged. |
In addition, testing was performed (following exposure to simulated shipping conditions and packaging testing) to verify that product design specifications were met at T=0. Bench performance testing completed is shown in Table 4.
| Table 4. Start-Up Kit Performance Testing | ||||
|---|---|---|---|---|
| -- | -- | -- | ------------------------------------------- | -- |
| Test Name | Test Method Summary | Results |
|---|---|---|
| SUK Flow Test | To verify that air flows through theSUK system. | Air flowed through all SUKsystems. |
| SUK High Pressure Leak Test | To verify no leaks below specifiedacceptance criteria. | No leaks were noted below thespecified pressure. |
| Modified SUK Indwell Life Test | To verify that Custom Luers andSUK Tubing are able to functionnormally at specified temperaturesfor the labeled indwell period. | All custom Luers and SUK tubingwere able to function normally for 7days at the specified temperature. |
| SUK Tubing to Luer Tensile | To verify that SUK Tubing andCustom Luers conform to EN ISO10555-1:2013 and minimumspecified acceptance criteria. | The tensile strength of all inflowand outflow tubes to Luers met therequirements of ISO 10555-1:2013. |
Bench Performance
Bench Performance Testing was conducted on samples of the Cool Line Intravascular Heat Exchange Catheter (as a representative model for all three catheters subject to the same modifications) to verify that product design specifications were met at T=0. The Luers and Extension tubings are identical in all models. Testing completed is shown in Table 5.
| Test Name | Test Method Summary | Results |
|---|---|---|
| Visual Inspection | Visual inspection to inspect for Luers, caps, and extension tubes for correct colors. | All Luer colors met the requirements of associated drawings. |
| Dimensional Measurement of Extension Tube Lengths | Verify dimensions of extension tube lengths. | All extension tubes met specific dimensional specifications. |
| Guidewire Passage | Verify ability to frontload, backload, and remove J-tip 0.032" guidewire from catheter. | The J-tip 0.032" guidewire was able to be frontloaded, backloaded, and removed from all catheters. |
| Ink Stability | Verify that pad printed ink does not smudge or come off when tested in accordance with specified acceptance criteria. | The pad printed ink on all infusion Luers remained legible after rubbing with alcohol. |
| Alcohol Resistance | Verify that Luers do not craze or crack when tested in accordance with specified acceptance criteria. | No Luers showed evidence of crazing or cracking after being soaked in alcohol. |
Table 5. Catheter Performance Testing
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| Test Name | Test Method Summary | Results |
|---|---|---|
| Balloon Deflation Using DeflationSyringe (20 mL Slip-Fit) | Verify that catheter balloonscollapse upon aspiration atspecified temperature usingsupplied slip-fit syringe. | All catheter balloons collapsedupon aspiration using the suppliedslip fit syringe. |
| Balloons Leakage Upon AspirationUsing the Supplied Deflation (20mL Slip-Fit) Syringe | To verify that catheter balloonsconform to EN ISO 10555-1:2013(must not show air leakage duringaspiration). | No air leakage was noted from thecatheter balloons during aspirationusing the supplied slip fit syringe. |
| Heat Exchange Power | To verify that the modifiedcatheters meet specified acceptancecriteria. | All catheters met the heat transferperformance requirement. |
| Ultimate Burst/Leak (All Luers) -Embolic Failure | To verify that catheter Luersconform to EN ISO 10555-1:2013(must meet minimum staticpressure at specified temperaturewithout embolic failure). | All catheters were able to withstand100-110 psi static pressure at 37°Cwithout embolic failure. |
| Catheter Inflow/Outflow CustomLuers connected to SUKInflow/Outflow Pressure Test | To verify that catheterinflow/outflow Luers andextensions withstand minimumstatic pressure for specified periodof time. | All Luers and extension tubes wereable to withstand a minimum staticpressure while connected to anSUK for a specified period of time. |
| Modified Catheter Indwell Life | To verify that catheter Luers andextensions are able to functionnormally for the labeled indwellperiod. | All Luers and extension tubes wereable to function normally for sevendays. |
| Extension Tubing to Luer Tensile. | To verify that extensiuon tubing toLuer joints conform to EN ISO10555-1:2013 (must meet minimumstrength) | All catheter joints demonstratedminimum tensile strength inaccordance with the requirementsof EN ISO 10555-1:2013 |
Where applicable, testing was performed in accordance with the following standards:
- . ISO 10555-1:2013 - Sterile, single-use intravascular catheters Part 1. General requirements
The results of design verification testing performed demonstrate that the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters meet their design performance specifications at T=0.
Additional testing was conducted as part of Testing to Luer Standards on the injection molded components used to manufacture the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters. Results of testing verify compliance to the following applicable standard:
-
ISO 594-1:1986 Conical fittings with a 6% (Luer) taper for syringes, needles and certain ● other medical equipment Part 1: General requirements
In addition, tests methods similar to those specified in the following standard were used to test the Custom Luers with Custom reference fittings: -
ISO 594-2:1998 Conical fittings with a 6% (Luer) taper for syringes, needles and certain ● other medical equipment Part 2: Lock fittings
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Testing completed is shown in Table 6.
| Test Name | Test Method Summary | Results |
|---|---|---|
| Critical Dimensions Inspection | Critical dimensions must meet the dimensional tolerances for the Critical dimensions, of the respective drawing | All samples met the dimensional tolerances for the critical dimensions. |
| Gauging | Tested using test method similar to test specified in ISO594-1&2 (§4.1) | All samples met the requirements of the test method used. |
| Water/Liquid Leakage | Tested using test method similar to test specified in ISO594-1&2 (§4.2.1) | All samples met the requirements of the test method used. |
| Air Leakage | Tested using test method similar to test specified in ISO594-2 (§4.2.2) | All samples met the requirements of the test method used. |
| Separation Force | Tested using test method similar to that specified in ISO594-2 (§4.3) | All samples met the requirements of the test method used. |
| Unscrewing Torque | Tested using test method similar to that specified in ISO594-2 (§4.4) | All samples met the requirements of the test method used. |
| Ease of Assembly | Tested using test method similar to that specified in ISO594-2 (§4.5 b) | All samples met the requirements of the test method used. |
| Resistance to Overriding | Tested using test method similar to that specified in ISO594-2 (§4.6) | All samples met the requirements of the test method used. |
| Stress Cracking | Tested using test method similar to that specified in ISO594-2 (§4.7) | All samples met the requirements of the test method used. |
Table 6. Luer Performance Testing
Based on the test results obtained, it can be concluded that all of the standard and custom catheter Luers, custom SUK Luers, and custom catheter vented caps are qualified for use in the assemblies used to manufacture the modified SUK and the modified Cool Line, ICY and Quattro Intravascular Heat Exchange Catheters.
Biocompatibility
To verify the biocompatibility of the modified Luers for the Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters. ZOLL conducted biocompatibility testing on the proximal (modified) portion of the catheter only. Similarly, to verify the biocompatibility of the modified SUK, ZOLL conducted biocompatibility testing on the SUK Custom Luers only. Biocompatibility testing was conducted in accordance with GLP regulations.
Because the Custom Molded Luer Set components located on the SUK and on the proximal end of the catheter only have indirect blood contact and prolonged exposure. ZOLL conducted testing based on the classification of an externally communicating device, blood path indirect for prolonged exposure (>24hrs and <30 days). Based on this classification, the following categories of biocompatibility tests were performed:
- Cytotoxicity
- Sensitization
- Irritation/Intracutaneous Reactivity ●
- Acute Systemic Toxicity
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- Hemocompatibility .
Test results are shown in Table 7.
| Test Category | Test Method Summary | Results |
|---|---|---|
| Cytotoxicity | MEM Elution Test | The reactivity grade of all testarticle extract samples was "0”. |
| Sensitization | ISO 10993 Part 10 Guinea PigMaximization Sensitization Test(GLP) | The test article extracts did notcause sensitization reactions underthe conditions of the assay. |
| Irritation | ISO/USP Intracutaneous ReactivityIrritation Test in Rabbits(GLP) | The data indicated that the testarticle extracts did not cause a skinirritation reaction. |
| Acute Systemic Toxicity | ISO/USP Medical Device AcuteSystemic Toxicity Test in Mice(GLP) | Based on the clinical observationsand body weight evaluations, thetest article (device) extracts did notshow significantly greaterbiological reaction than the controlarticle extracts. |
| Material Mediated Pyrogen | ISO/USP Materials MediatedPyrogen Test in Rabbits(GLP) | None of the animals in the studyshowed abnormal clinical signsprior to dose administration orduring the observation period andno animals showed a temperatureincrease of 0.5°C or greater duringthe study period. |
| Hemocompatibility | ASTM Hemolysis (Extract Method)Test (GLP) | The difference between thehemolytic indexes of the test articleand the negative control equals 0.00percent. This places the test articlein the non-hemolytic range. All testmethod acceptance criteria weremet. |
| Hemocompatibility | Complement Activation Test(GLP) | C3a: The P value was >0.050when the test article was comparedto the predicate at the 30, 60, and90 minute time points; the testarticle and predicate are statisticallysimilar at these time points.The P value was >=0.050 when thetest article was compared to thenegative control at the 30, 60, and90 minute time points; the testarticle and predicate are statisticallysimilar at these time points.SC5b-9: The P value was >0.050when the test article was comparedto the predicate at the 30, 60, and90 minute time points; the testarticle and predicate are statisticallysimilar at these time points. |
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| Test Category | Test Method Summary | Results |
|---|---|---|
| The P value was ≥0.050 when thetest article was compared to thenegative control at the 30 and 60minute time points; the test articleand negative control are statisticallysimilar at these time points. The Pvalue was ≤0.050 when the testarticle was compared to thenegative control at the 90 minutetime point; the test article isstatistically lower than the negativecontrol at this time point. |
The results of the testing demonstrate that the modified SUK and the modified Cool Line. ICY . and Quattro Intravascular Heat Exchange Catheters are biocompatible for their intended use and the modifications made to the subject devices do not adversely affect the established biocompatibility of the predicate devices.
Usability/Human Factors
Pursuant to the FDA guidance document titled "Draft Guidance for Industry and Food and Drug Administration Staff - Applying Human Factors and Usability Engineering to Optimize Medical Device Design" Human Factors testing was conducted as follows:
Summary of Formative Testing 1.
Human factors formative testing was performed to determine if users trained according to the IFU can properly perform the following:
- Identify infusion lumens, (proximal, medial, and distal) ●
- . Properly connect the IN and OUT Luers to the Start-Up Kit (SUK)
- Identify the saline IN and OUT Luers ●
- Identify any lumen that is appropriate for pharmacological infusate. ●
- Disconnect the Saline IN and OUT track (SUK Luers) including evacuating the saline . from the catheter using a syringe.
User tasks were based on identifying and (or) making proper connections as documented in the Formative Human Factors Protocol for ZOLL Custom Luers. The test session ran over the course of two days.
Four scenarios were presented, and participants were evaluated based on 14 predefined success metrics. All participants correctly executed each scenario, with no failures. All participants who received representative level of training and had access to the IFU successfully completed all of the tasks. This indicates that the device design, training content and the IFU adequately mitigate the risk of misconnections. No device design, training or IFU modifications were indicated based on this formative test.
2. Summary of Summative Testing
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Human factors summative testing was performed to evaluate if users trained according to the ZOLL Custom Luer Training Program and IFU can properly perform the following:
- Match the new catheter and new Start-Up Kit (SUK) with custom Luers
- Place 20 cc syringe on saline hook on TGXP (Thermogard XP) console ●
- Connect the IN and OUT Luers on the catheter to its counterpart on the SUK .
- . Select an infusion lumen for an IV infusion
- . Use 20 cc syringe for aspiration of saline after a catheter is used as a CVC after temperature management therapy ends
- Aspirate saline prior to catheter removal. .
A total of five scenarios were presented, and each participant had to correctly answer questions 9-13 to achieve a passing score. All other questions (1-8, 14-15) required a minimum of an 80% passing score. The acceptance criteria were met with 100% of the users passing the critical tests (9-13). All of the non-critical items (1-8 and 14-15) were passed with at least 12 participants passing (80%).
All participants who received training and followed the IFU successfully met the acceptance criteria. This testing confirms that the custom Luer design, training, and IFU facilitate appropriate catheter and SUK connections. No device design, training or IFU modifications were indicated based on the summative evaluation.
V. Summary of Clinical Tests Performed
Clinical evaluations were not performed for the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters because such evaluations were not necessary to demonstrate substantial equivalence of the modified devices to the predicate devices (SUK: K014241; Catheters: K101987).
VI. Substantial Equivalence
The modified SUK and the modified Cool Line. ICY, and Quattro Intravascular Heat Exchange Catheters have the same intended use / indications for use as the 510(k) cleared SUK (K014241) and the 510(k) cleared Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters; Catheters (K101987). The results of the packaging validation (SUK only), bench performance, biocompatibility, and usability testing demonstrate that the modifications do not affect the performance or function of the devices. The minor differences in the design between the modified and cleared devices, do not raise any new types of safety or effectiveness questions as confirmed by design verification testing. Therefore, the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters are substantially equivalent to the previously cleared predicate devices.
VII. Conclusions
ZOLL concludes that based on the results of the packaging validation, bench performance, biocompatibility and usability testing performed, the modified SUK and the modified Cool Line, ICY, and Quattro Intravascular Heat Exchange Catheters are substantially equivalent to the predicate devices.
§ 870.5900 Thermal regulating system.
(a)
Identification. A thermal regulating system is an external system consisting of a device that is placed in contact with the patient and a temperature controller for the device. The system is used to regulate patient temperature.(b)
Classification. Class II (performance standards).