(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: 0.74
ICH: 1.00
PTBI: 0.24
SAH: 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.
§ 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).