The NxStage System One is indicated for the treatment of acute and chronic renal failure, or fluid overload using hemofiltration, hemodialysis, and/or ultrafiltration, in an acute or chronic care facility.
The System is also indicated for home hemodialysis, including home nocturnal hemodialysis.
All treatments must be administered under physician's prescription, and must be performed by a trained and qualified person, considered to be competent in the use of this device by the prescribing physician.

Device Description

The NxStage System One is comprised of the NxStage Cycler, an electromechanical control unit; the NxStage Cartridge, a sterile, single-use extracorporeal blood and fluid management circuit (with or without a preattached high permeability filter) that mounts integrally within the NxStage Cycler. The combined system is designed to deliver hemofiltration, hemodialysis and/or ultrafiltration in an acute or chronic care facility. The NxStage System One is also indicated for home hemodialysis, including home nocturnal hemodialysis.

AI/ML Overview

This document describes the NxStage System One, a hemodialysis system. The FDA 510(k) clearance (K141752 dated December 19, 2014) indicates that the device is substantially equivalent to a previously cleared NxStage System One (K140526).

Here's an analysis of the provided information regarding acceptance criteria and the study that proves the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the chosen "primary effectiveness endpoint" and "primary safety endpoint" of the pivotal clinical study.

Acceptance Criteria	Reported Device Performance (NxStage System One)
Effectiveness (Primary Endpoint): Ability to deliver the clinically prescribed amount of therapy, defined by attainment of a delivered volume that is at least 90% of the prescribed volume. Performance is deemed successful if the upper boundary of the 95% confidence interval of the difference in success rates between NHD and DHD is less than 10%.	Effectiveness: Probability of successful treatment: 90.9% in Daily Hemodialysis (DHD) phase vs. 91.7% in Nocturnal Hemodialysis (NHD) phase. The upper limit of the confidence interval (2.9%) was less than the protocol-specified limit (10%). This met the non-inferiority criterion.
Safety (Primary Endpoint): Composite intradialytic and interdialytic adverse event (AE) profile. The study aimed to show similarity in AE rates between NHD and DHD.	Safety: Composite AE rate per 100 treatments: 8.3 in DHD phase vs. 6.9 in NHD phase. The event profiles were similar for both phases. No unanticipated adverse device effects and one death not related to the study device. Rate of severe AEs per 100 treatments: 0.9 for DHD vs. 0.3 for NHD.

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

Sample Size: A total of 58 End Stage Renal Disease (ESRD) patients participated in the clinical study. 39 completed the study period, and 19 discontinued.
Data Provenance: The study was a US prospective, multi-center clinical study.

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

This information is not explicitly provided in the document. The "ground truth" for the clinical study was based on patient outcomes, delivered therapy volumes, and reported adverse events during the observational clinical trial. The study was conducted "under physician's prescription," implying medical oversight, but specific details about expert adjudication for individual patient data points are not detailed.

4. Adjudication Method for the Test Set

This information is not explicitly provided. The clinical study collected data on delivered therapy and adverse events. The assessment of these outcomes would have been part of the clinical trial protocol, but there is no specific mention of an independent adjudication committee for all events or for the effectiveness endpoint.

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

This question is not applicable to the provided document. The NxStage System One is a hemodialysis device, not an AI-powered diagnostic or interpretive tool that would involve human readers or AI assistance in the interpretation of medical images or data. The study compared two different treatment regimens (Nocturnal Hemodialysis vs. Daily Hemodialysis) using the same device, not human performance with and without AI.

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

This question is not applicable. The device is a hemodialysis system, not an algorithm, and it always involves a human-in-the-loop (trained and qualified person, prescribing physician, and patient). The "effectiveness" measurement was based on the system's ability to deliver therapy, not an independent algorithmic output.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The ground truth for the clinical study was based on patient outcomes data, specifically:

Effectiveness: Measured by the actual delivered volume of therapy compared to the prescribed volume.
Safety: Measured by the occurrence and rates of intradialytic and interdialytic adverse events.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning or AI. For the clinical study, the patients (all 58 of them) effectively served as the "test set" for evaluating the performance of the device in the two different treatment regimens. If "training set" refers to data used for initial device development and non-clinical testing, that information is not detailed here beyond "System Verification and Software Validation" and "Simulated dialysis treatments."

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

As there is no explicit "training set" described in the context of a machine learning or AI algorithm, this question is not fully applicable. For the non-clinical testing (System Verification and Software Validation, Regression testing, etc.), the ground truth would have been established through engineering specifications, validated test protocols, and simulated conditions to ensure the device performs as designed.

Summary

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Re:

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 19, 2014

NxStage Medical, Inc. Mary Lou Strombos Director, Regulatory Affairs 350 Merrimack Street Lawrence. MA 01843

K141752 Trade/Device Name: NxStage System One Regulation Number: 21 CFR 876.5860 Regulation Name: High Permeability Hemodialysis System Regulatory Class: Class II Product Code: ODN Dated: November 20, 2014 Received: November 21, 2014

Dear Mary Lou Strombos,

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. 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 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in

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the quality systems (OS) 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 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,

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for

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE

510(k) Number (if known): K141752

NxStage® System One™ Device Name:

Indications for Use: The NxStage System One is indicated for the treatment of acute and chronic renal failure, or fluid overload using hemofiltration, hemodialysis, and/or ultrafiltration, in an acute or chronic care facility.
The System is also indicated for home hemodialysis, including home nocturnal hemodialysis.

All treatments must be administered under physician's prescription, and must be performed by a trained and qualified person, considered to be competent in the use of this device by the prescribing physician.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Page 1 of 1

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This 510(k) Summary is being submitted in accordance with the requirements of the Safe Medical Device Act (SMDA) of 1990. The content contained in this 510(k) summary has been provided in conformance with 21 CFR §807.92

A. Date Prepared:	June 27, 2014
B. Submitter's Information:Name:	NxStage Medical, Inc.
Address:	350 Merrimack StreetLawrence, MA 01843
FDA EstablishmentOwner/OperatorNumber:	9045797
Contact Person:	Mary Lou StroumbosDirector, Regulatory Affairs
Phone:Fax:	(978) 687-4872(978) 687-4750
Manufacturer:	NxStage Medical, Inc.350 Merrimack StreetLawrence, MA 01843
FDA EstablishmentRegistration Number:	3003464075
Sterilization Site:	Steris Isomedix (NxStage CartridgeExpress)1000 S. Sarah PlaceOntario, CA 91761

Traditional 510(k) Premarket Notification NxStage Medical, Inc.

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NxStage Medical, Inc. NxStage System One 510(k) Premarket Notification

C. Device Name: Trade/Proprietary NxStage System One Name: Common/Usual Name: Hemodialysis System Classification Name: High Permeability Hemodialysis System Regulation Number: 876.5860 Product Code: ODN Device Classification: Class II Device Panel: Gastroenterology/Urology

D. Substantial Equivalence:

The NxStage System One has the same intended use and utilizes the same fundamental technology as the predicate NxStage System One. The NxStage System One has been compared to the legally marketed predicate device as cleared through K140526 (May 19, 2014) and was found to be substantially equivalent.

E. Device Description/Indications for Use:

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Indications for use:

The NxStage System One is indicated for the treatment of acute and chronic renal failure or fluid overload using hemofiltration, hemodialysis, and/or ultrafiltration, in an acute or chronic care facility.

The System is also indicated for home hemodialysis, including home nocturnal hemodialysis.

F. Technological Characteristics:

The proposed device has the same technological characteristics and is similar in design and configuration as compared to the predicate device. The proposed device is designed with similar software, components and features also used in the predicate device.

Table 1Device Technological Characteristics Comparison Table
Parameter	Proposed DeviceNxStage System One	Predicate DeviceNxStage System One(K140526)
Intended UseHemodialysis	Yes	Yes
Hemofiltration	Yes	Yes
Ultrafiltration	Yes	Yes
Technology / Components:
Pumps	Same	4 peristaltic pumps
Valves (clamps)	Same	2 solenoid actuated pinch clamps
	Same	8 cam driven pinch clamps
Air / fluid detectors	Same	3 ultrasonic air/ fluid detectors
Blood leak detector	Same	1 optical blood leak detector
Pressure transducers	Same	5 electronic pressure transducers
Temperature sensors	Same	1 electronic temperature sensor

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NxStage Medical, Inc. NxStage System One 510(k) Premarket Notification

Table 1Device Technological Characteristics Comparison Table
Parameter	Proposed DeviceNxStage System One	Predicate DeviceNxStage System One(K140526)
Flow Rates:Blood	Same	10-600 ml/min
Prescription Fluid /DialysateFlow	Same	0-18000 ml/hr
Ultrafiltration	Same	0-2400 ml/hr
Transmembrane PressureMonitoring Specification	Same	Yes
Venous Pressure Monitor	Same	0 to 400 mmHg
Effluent fluid Pressure Monitor	Same	0 to 500 mmHg
Air Detector	Same	Reduction of detector signal lasting 6 msminimum (Approximates a 60 micro literbubble at 400 mmHg venous pressure and600 ml/min blood flow)
Blood Leak Detector	Same	15% reduction in detector signal lasting 20seconds minimum. Signal reduction %based on a 0.35 ml/min leak rate of 32 Hctblood.
Effluent Volume Accuracy	Same	Greater of 300 ml/ 12 hr or 3% of exchangevolume (For software versions 4.7 andbelow)For software versions 4.8 and higher:Therapy Fluid Flow Rate L/hr) Specification greater of > 3 $\pm$ 100 ml/hror+ 5% UF ≤ 3 $\pm$ 25 ml/hr* *Representing 95/90 tolerance intervalestablished under controlled laboratorytesting conditions.
IV Prescription Fluid	Same	Off-line, sterile- physician prescribed,indicated for infusion
Dialysate	Same	Dialysate available as pre-packaged pre-mixed sterile fluids or via the PureFlow SL(K043436 K060296, K090919, K111174 &K140571)
Compatible Blood Tubing Set	Same	NxStage Standard Cartridge
Software	Software version 4.10	Software version 4.9

Traditional 510(k) Premarket Notification NxStage Medical, Inc.

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Summary of Non-Clinical Test/Performance Testing – Bench and G. Clinical Testing

NxStage believes that the information and data provided in this submission clearly describes the proposed device and demonstrates that the device is adequately designed for the labeled indications for use. Performance, verification and validation; and clinical testing was conducted to characterize performance of the proposed device and the predetermined acceptance criteria were met.

The following non-clinical testing was conducted:

. System Verification and Software Validation
- Software verification & validation o
- Regression testing o
- Safety systems verification o
- Labeling verification testing O
- Simulated dialysis treatments O

The following clinical testing was conducted:

Clinical testing included 2 crossover studies with a total of 58 patients. There were 38 in the first study and 20 in the second study. Results were provided separately and pooled together to show substantial equivalence of nocturnal hemodialysis to daily hemodialysis in the home setting.

Pivotal Studies:

NxStage conducted a US prospective, multi-center, two-treatment, twophase, open-label, cross-over Investigational Device Exemption clinical study titled "Comparison of Nocturnal Hemodialysis (NHD) and Short Daily Hemodialysis (DHD) with the NxStage System One." The objective of the study was to determine whether or not NHD (6-10 hours) was substantially equivalent to DHD (2-4 hours) on a per treatment basis, using the NxStage System One (NSO) in the home setting. The first phase (DHD) consisted of 2 to 4 hour treatments, and the second phase (NHD) consisted of 6 to 10 hour treatments. Both phases consisted of either 5 or 6 treatments per week over an 8 week period (40 or 48 treatments in total) using the NSO in the home environment. A 4 week training/transition period took place between the two phases. A total of 58 End Stage Renal Disease (ESRD)

Traditional 510(k) Premarket Notification NxStage Medical, Inc.

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patients >18 years of age who were currently stable on home DHD were enrolled, of which 39 completed the study period and 19 discontinued.

Primary effectiveness endpoint:

The primary efficacy endpoint for the study was the ability to deliver the clinically prescribed amount of therapy, defined by attainment of a delivered volume that was at least 90% of the prescribed volume (10% difference in success rate is the upper boundary of the 95% confidence interval).

Primary safety endpoint:

The primary safety endpoint was the composite intradialytic and interdialytic adverse event (AE) profile.

Effectiveness:

The primary endpoint for the study focused on the ability to deliver the clinically prescribed amount of therapy (success or failure). For the ITT population, the probability of a successful treatment was 90.9% in the DHD phase versus 91.7% in the NHD phase. The upper limit of the confidence interval (2.9%) was less than the protocol-specified limit (10%). Hence, the treatment success rates were similar and the protocol specified noninferiority criterion was attained.

Safety:

For the ITT population, the composite AE rate per 100 treatments was 8.3 in the DHD phase versus 6.9 in the NHD phase. The event profiles were similar for both phases. Results were similar for the PP population.

The study reported one death not related to study participation or the study device and no unanticipated adverse device effects. In the DHD phase there were 21 severe AEs reported, and in the NHD phase there were 6 severe AEs reported. Device relatedness was recorded as cannot be ruled out for one of the severe AEs: patient was unable to self-cannulate due to a non-dialysis related surgery. The remaining 26 severe AEs were considered not related to the device. The rate of severe AEs per 100 treatments was 0.9 for DHD vs. 0.3 for NHD.

Traditional 510(k) Premarket Notification NxStage Medical, Inc.

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The most commonly occurring AEs were OTH-other, hypotension, and muscle cramping. OTH-other included non-dialysis related injuries and surgeries (e.g. broken ankle, knee surgery, toe infection, etc.), out of range blood laboratory values, access related events, episodes of depression, infection, kidney stone, and other isolated events. OTH-other occurred at a rate of 1.3 vs. 1.6 per 100 treatments in DHD vs. NHD, respectively. Hypotension occurred at a rate of 1.9 vs. 0.2 per 100 treatments. The rate of muscle cramping was 1.1 per 100 treatments for both study phases.

The rates of adverse events were similar in the DHD and NHD phases, and the events experienced were typical of those commonly reported for dialysis patients, including episodes of hypotension and muscle cramping.

Summary

Based on the clinical performance as documented in the pivotal clinical studies, the NxStage System One in the home setting delivers NHD therapy that is substantially equivalent to DHD therapy on a per treatment basis.

Conclusion: Results of the non-clinical testing and clinical data have documented that the proposed NxStage System One is substantially equivalent to the predicate device and is suitable for the labeled indications for use.

Regulation Number and Section

§ 876.5860 High permeability hemodialysis system.

(a)
Identification. A high permeability hemodialysis system is a device intended for use as an artificial kidney system for the treatment of patients with renal failure, fluid overload, or toxemic conditions by performing such therapies as hemodialysis, hemofiltration, hemoconcentration, and hemodiafiltration. Using a hemodialyzer with a semipermeable membrane that is more permeable to water than the semipermeable membrane of the conventional hemodialysis system (§ 876.5820), the high permeability hemodialysis system removes toxins or excess fluid from the patient's blood using the principles of convection (via a high ultrafiltration rate) and/or diffusion (via a concentration gradient in dialysate). During treatment, blood is circulated from the patient through the hemodialyzer's blood compartment, while the dialysate solution flows countercurrent through the dialysate compartment. In this process, toxins and/or fluid are transferred across the membrane from the blood to the dialysate compartment. The hemodialysis delivery machine controls and monitors the parameters related to this processing, including the rate at which blood and dialysate are pumped through the system, and the rate at which fluid is removed from the patient. The high permeability hemodialysis system consists of the following devices:(1) The hemodialyzer consists of a semipermeable membrane with an in vitro ultrafiltration coefficient (K
uf ) greater than 8 milliliters per hour per conventional millimeter of mercury, as measured with bovine or expired human blood, and is used with either an automated ultrafiltration controller or anther method of ultrafiltration control to prevent fluid imbalance.(2) The hemodialysis delivery machine is similar to the extracorporeal blood system and dialysate delivery system of the hemodialysis system and accessories (§ 876.5820), with the addition of an ultrafiltration controller and mechanisms that monitor and/or control such parameters as fluid balance, dialysate composition, and patient treatment parameters (e.g., blood pressure, hematocrit, urea, etc.).
(3) The high permeability hemodialysis system accessories include, but are not limited to, tubing lines and various treatment related monitors (e.g., dialysate pH, blood pressure, hematocrit, and blood recirculation monitors).
(b)
Classification. Class II. The special controls for this device are FDA's:(1) “Use of International Standard ISO 10993 ‘Biological Evaluation of Medical Device—Part I: Evaluation and Testing,’ ”
(2) “Guidance for the Content of 510(k)s for Conventional and High Permeability Hemodialyzers,”
(3) “Guidance for Industry and CDRH Reviewers on the Content of Premarket Notifications for Hemodialysis Delivery Systems,”
(4) “Guidance for the Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis,” and
(5) “Guidance for Hemodialyzer Reuse Labeling.”