Kidney Failure, Chronic
Conditions
Brief summary
Endexo™ is an additive that is blended into the fiber solution during manufacturing of the hemodialyzer hollow fibers. The intended purpose of the additive is to increase blood compatibility in the finished dialyzer, which is referred to as the dialyzer with Endexo.
Detailed description
This is a prospective, sequential, multi-center, open-label study with subjects on thrice-weekly (in-center) hemodialysis (HD). After a Screening Period, there will be 12 hemodialysis treatments on the Optiflux dialyzer (Optiflux Period), followed by 38 HD treatments on the dialyzer with Endexo (Endexo Period), and then a Follow-up Visit. The study population will consist of End-Stage Renal Disease ESRD subjects who are a minimum of 22 years of age. The primary objective of the study is to collect data on the performance of the dialyzer with Endexo when used to perform hemodialysis (HD) in End-Stage Renal Disease (ESRD) subjects.
Interventions
DEVICEOptiflux and Dialyzer with Endexo
Hemodialysis (HD) on Optiflux dialyzer from Visit 1 to 12 and followed by HD on the dialyzer with Endexo at visit 13 and continues until visit 50. Dialysis is performed 3 times per week which means the total of the intervention will be 17 weeks.
Sponsors
Fresenius Medical Care North America
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
12 HD treatments (4 weeks) with Optiflux dialyzer followed by 38 HD treatments (13 weeks) with Endexo dialyzer
Eligibility
Sex/Gender
ALL
Age
22 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Must be an adult, older than 22 years of age. 2. Has been prescribed in-center thrice-weekly HD continuously for at least 180 days prior to the date of signed informed consent 3. Has been prescribed the Optiflux F160NR dialyzer continuously for at least 30 days prior to the date of signed informed consent 4. Has a prescribed HD treatment time ≥180 minutes (3 hours) and ≤270 minutes (4.5 hours) 5. Has been on heparin anticoagulation for dialysis and has had no change in heparin prescription within 14 days prior to the date of signed informed consent 6. Has a most recent single pool Kt/V (spKt/V) ≥1.2 within 45 days prior to the date of a signed informed consent 7. Has a most recent hemoglobin ≥9 g/dL within 45 days prior to the date of a signed informed consent 8. Has a most recent platelet count ≥100,000/mm3 within 45 days prior to the date of a signed informed consent 9. A female of childbearing potential must have a negative serum pregnancy test at the time of screening and agree to use an acceptable method of contraception during the study
Exclusion criteria
1. Use of citric acid concentrate (such as Citrasate®) at the time of signed informed consent 2. Known allergic reactions to Endexo 3. Hospitalization within 30 days prior to the date of signed informed consent 4. Presence of active malignancy, congestive heart failure New York Heart Association (NYHA) Class III or IV, or liver cirrhosis 5. Are receiving or have received chemotherapy / radiation therapy / plasmapheresis therapy within 90 days prior to the date of signed informed consent 6. Are receiving antibiotics or have used antibiotics within 14 days prior to the date of signed informed consent 7. Are currently enrolled in or have completed any other investigational product study within 30 days prior to the date of signed informed consent 8. Has a life expectancy of less than 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Performance of the Dialyzer With Endexo by Measuring Its in Vivo Ultrafiltration Coefficient | 15 minutes after the recorded start of hemodialysis with Endexo upon its first use in the study | Ultrafiltration coefficient (Kuf) is the ratio of ultrafiltration rate in ml/hr to the Transmembrane pressure in mmHg. Both the Ultrafiltration rate and the transmembrane pressure readings are collected from the machine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Any Adverse Events | Optiflux: from enrollment, weeks 1 to 4 (visits 1 to 12); Endexo: from weeks 5 to 17, and follow-up, a total of 17 weeks intervention. | All adverse events were captured from subject enrollment to the completion of Optiflux period, and to the end of study or withdraws from the study. |
| The Number of Any Device-related Adverse Events | Optiflux: from enrollment, weeks 1 to 4 (visits 1 to 12); Endexo: from weeks 5 to 17, and follow-up, a total of 17 weeks intervention. | Any device-related adverse events were captured from subject enrollment to the completion of Optiflux period, and to the end of study or withdraws from the study. |
| Removal of Urea | At visits 1/week 1, 10/week 4, 13/week 5, 22/week 8, 34/week 12, and 46/week 16 | 1. URR = (pre-HD urea - post-HD urea)/pre-HD urea \* 100 2. Data across visits were averaged for each subject, and then a group mean and sd were calculated. |
| Removal of Albumin | Pre- and Post- HD at Visits 1/week 1, 13/week 5 | %change = (post-HD - pre-HD)/pre-HD \* 100 |
| Removal of Beta-2-microglobulin | Pre- and Post- HD at Visits 1/week 1, 13/week 5 | % reduction = (post-HD - pre-HD)/pre-HD \* 100 with post-HD B2M adjusted to pre- and post HD weights |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dialyzer Hemocompatibility | Assessed at the first time the dialyzers are used in the study , collected pre hemodialysis and 30 minutes after the recorded start of hemodialysis | The dialyzer hemo-compatibility is measured by measuring the activation of the complement system (C3a, C5a, SC5b-9) |
| Clotting of the Dialyzer | visual evaluation of the dialyzer arterial cap will be performed at the end of every hemodialysis treatment to determine the Grade:1,2,3 or 4. (1:no clotting to 4: total clotting), throughout a total of 17 weeks intervention. | Thrombus scoring will be assessed according to a clotting scale (The graded scoring method) |
Countries
United States
Participant flow
Recruitment details
Hemodialysis patients were recruited at three clinical sites in the USA. 23 subjects were enrolled to this study. The first subject first visit was on August 29, 2018 and the last subject last visit was on April 17, 2019.
Participants by arm
| Arm | Count |
|---|---|
| Endexo Hemodialysis treatments on the dialyzer with Endexo starts at visit 13 and continues until visit 50. Dialysis is performed 3 times per week which means the total of the intervention is approximately 13 weeks.
Dialyzer with Endexo: Hemodialysis treatments on the dialyzer with Endexo starts at visit 13 and continues until visit 50. Dialysis is performed 3 times per week which means the total of the intervention is approximately 13 weeks. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Endexo | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Endexo |
|---|---|
| Age, Continuous | 60.28 years STANDARD_DEVIATION 14.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 18 |
| other Total, other adverse events | 4 / 23 | 11 / 18 |
| serious Total, serious adverse events | 0 / 23 | 3 / 18 |
Outcome results
Primary
Performance of the Dialyzer With Endexo by Measuring Its in Vivo Ultrafiltration Coefficient
Ultrafiltration coefficient (Kuf) is the ratio of ultrafiltration rate in ml/hr to the Transmembrane pressure in mmHg. Both the Ultrafiltration rate and the transmembrane pressure readings are collected from the machine.
Time frame: 15 minutes after the recorded start of hemodialysis with Endexo upon its first use in the study
Population: Subjects who are in the safety population, and have a minimum of 36 HD treatments with the dialyzer with Endexo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endexo | Performance of the Dialyzer With Endexo by Measuring Its in Vivo Ultrafiltration Coefficient | 16.36 mL/hr/mmHg | Standard Deviation 9.92 |
Secondary
Removal of Albumin
%change = (post-HD - pre-HD)/pre-HD \* 100
Time frame: Pre- and Post- HD at Visits 1/week 1, 13/week 5
Population: Subjects who are in the safety population, and have a minimum of 36 HD treatments with the dialyzer with Endexo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endexo | Removal of Albumin | 7.89 percent change | Standard Deviation 8.63 |
| Endexo | Removal of Albumin | 7.99 percent change | Standard Deviation 7.25 |
Secondary
Removal of Beta-2-microglobulin
% reduction = (post-HD - pre-HD)/pre-HD \* 100 with post-HD B2M adjusted to pre- and post HD weights
Time frame: Pre- and Post- HD at Visits 1/week 1, 13/week 5
Population: Subjects who are in the safety population, and have a minimum of 36 HD treatments with the dialyzer with Endexo.~One subject in this pop did not have lab results for pre- and post beta-2-microglobulin in Endexo period. Therefore n=16 instead of 17.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endexo | Removal of Beta-2-microglobulin | 46.86 percent reduction, corrected | Standard Deviation 7.16 |
| Endexo | Removal of Beta-2-microglobulin | 67.73 percent reduction, corrected | Standard Deviation 16.32 |
Secondary
Removal of Urea
1. URR = (pre-HD urea - post-HD urea)/pre-HD urea \* 100 2. Data across visits were averaged for each subject, and then a group mean and sd were calculated.
Time frame: At visits 1/week 1, 10/week 4, 13/week 5, 22/week 8, 34/week 12, and 46/week 16
Population: Subjects who are in the safety population, and have a minimum of 36 HD treatments with the dialyzer with Endexo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endexo | Removal of Urea | 80.81 percentage | Standard Deviation 4.33 |
| Endexo | Removal of Urea | 81.87 percentage | Standard Deviation 5.91 |
Secondary
The Number of Any Adverse Events
All adverse events were captured from subject enrollment to the completion of Optiflux period, and to the end of study or withdraws from the study.
Time frame: Optiflux: from enrollment, weeks 1 to 4 (visits 1 to 12); Endexo: from weeks 5 to 17, and follow-up, a total of 17 weeks intervention.
Population: Subjects who sign the ICF, are eligible, are enrolled in the study for Optiflux, and have at least one HD treatment with Endexo dialyzer for Endexo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Endexo | The Number of Any Adverse Events | 7 events |
| Endexo | The Number of Any Adverse Events | 32 events |
Secondary
The Number of Any Device-related Adverse Events
Any device-related adverse events were captured from subject enrollment to the completion of Optiflux period, and to the end of study or withdraws from the study.
Time frame: Optiflux: from enrollment, weeks 1 to 4 (visits 1 to 12); Endexo: from weeks 5 to 17, and follow-up, a total of 17 weeks intervention.
Population: Subjects who sign the ICF, are eligible, are enrolled in the study for Optiflux, and have at least one HD treatment with Endexo dialyzer for Endexo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Endexo | The Number of Any Device-related Adverse Events | 0 participants, events |
| Endexo | The Number of Any Device-related Adverse Events | 0 participants, events |
Other Pre-specified
Clotting of the Dialyzer
Thrombus scoring will be assessed according to a clotting scale (The graded scoring method)
Time frame: visual evaluation of the dialyzer arterial cap will be performed at the end of every hemodialysis treatment to determine the Grade:1,2,3 or 4. (1:no clotting to 4: total clotting), throughout a total of 17 weeks intervention.
Other Pre-specified
Dialyzer Hemocompatibility
The dialyzer hemo-compatibility is measured by measuring the activation of the complement system (C3a, C5a, SC5b-9)
Time frame: Assessed at the first time the dialyzers are used in the study , collected pre hemodialysis and 30 minutes after the recorded start of hemodialysis