Chronic Kidney Diseases, Patient Requiring Heparin Free Dialysis Treatments
Conditions
Brief summary
This study will assess the safety and efficacy of heparin free hemodialysis (HD) performed with dialyzers with Endexo in adult end-stage renal disease (ESRD) subjects on thrice-weekly in-center HD.
Interventions
DEVICEDialyzer with Endexo
Sequence AB: Period 1 Circuit A (Five Visits: 1,2,3,4,5) Period 2 Circuit B (Five Visits: 9,10,11,12,13) Sequence BA: Period 1 Circuit B (Five Visits: 1,2,3,4,5) Period 2 Circuit A (Five Visits: 9,10,11,12,13)
Sponsors
Fresenius Medical Care North America
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Must be an adult, defined as having had a 22nd birthday on or before the date of signed informed consent 2. Has been prescribed in center thrice weekly HD for at least 180 days prior to the date of signed informed consent 3. Has been on Conventional HD for at least 30 days prior to the date of signed informed consent. Conventional HD includes: Optiflux dialyzer (F160NR or F180NR), standard of care (SOC) bloodline, Citrasate dialysate, and regularly prescribed heparin dose. 4. Has a prescribed HD treatment duration ≥ 180 minutes (3 hours) and ≤ 270 minutes (4.5 hours) at the time of signed informed consent 5. Has a well-established functional permanent vascular access (AVF, AVG) that can allow a blood flow of at least 250 mL/min 6. Has been on a regularly prescribed heparin dose for HD and has had no change in heparin prescription within 14 days prior to the date of signed informed consent 7. Has the following most recently available laboratory results within 45 days prior to the date of signed informed consent: 1. Single pool Kt/V (spKt/V) ≥ 1.2 2. Hemoglobin ≥ 9 g/dL 3. Platelet count ≥ 100,000/mm3 8. 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. Known allergic reactions to Endexo 2. Known heparin contraindications 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 (see Appendix II. A New York Heart Association Functional Classification), or liver cirrhosis 5. Is receiving or has received chemotherapy/radiation therapy/immunotherapy/plasmapheresis therapy within 90 days prior to the date of signed informed consent 6. Is receiving oral or/and intravenous (IV) antibiotics or has used oral or/and IV antibiotics within 14 days prior to the date of signed informed consent 7. Is currently enrolled in or has completed any other investigational product study within 30 days prior to the date of signed informed consent 8. Is receiving anticoagulants including vitamin K antagonists 9. Is receiving a glycoprotein platelet inhibitor 10. Is receiving more than one anti-platelet medication 11. Is receiving systemic heparin therapy for prevention or treatment besides heparin prescribed for dialysis 12. Requiring blood and other labile blood products (for e.g., fresh frozen plasma, platelets) transfusion during HD treatments 13. Has history of clotting or bleeding disorders 14. Has history or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the participant's ability to follow the requirements of the study and participate for the full duration of the study, or is not in the best interest of the subjects to participate, in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Endpoint is the Number and Percent (%) of Successful Heparin-free HD Sessions for Each Subject in Each Circuit. | Approximately 5 weeks, Period 1: two weeks with either Circuit A or Circuit B; Washout: 1 week; Period 2: two weeks with the circuit other than Period 1. | Each participant was expected to receive 3 heparin-free HD sessions. The number and percentage of successful HD sessions were derived based on the 3 heparin-free HD sessions for each participant in each circuit. A successful HD session must meet all the following criteria: 1. Absence of complete HD circuit occlusion (Grade 4) rendering dialysis impossible 2. Absence of the need to replace dialyzers or bloodlines due to clotting 3. Absence of saline flushes to maintain blood flow through the circuit during the HD session 4. Absence of any additional heparin beyond what is allowed per study visits 5. Single pool Kt/V (spKt/V) ≥ 1.2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Secondary Endpoints Include Adverse Events . | two weeks each period (10 weeks per subject: 4 weeks for screening, 2 weeks for Period 1, 1 week for Washout, and 2 weeks for Period 2) | The number of Serious Adverse Events and Adverse Events during the study periods |
| The Secondary Endpoints Include Device-related Adverse Events. | two weeks each period (10 weeks per subject: 4 weeks for screening, 2 weeks for Period 1, 1 week for Washout, and 2 weeks for Period 2) | All device-related serious adverse events and adverse events occurred during the study periods |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Volume of Saline Administered Per Subject Per HD Session (Other Than for Circuit Priming or Rinse Back). | Approximately 4.5 hours | The volume of saline administered per subject per HD session (other than for circuit priming or rinse back). The total volume was calculated for each HD session. |
| The Time of Saline Administered Per Subject Per HD Session (Other Than for Circuit Priming or Rinse Back). | Approximately 4.5 hours | The time of saline administered per subject per HD session (other than for circuit priming or rinse back) during a HD session. |
| Number and Percentage of Dialyzers and Blood Lines for Each Clotting Grade Using the Visual Inspection Clotting Grade Scale | Approximately 5 weeks | Number and percentage of dialyzers (arterial end cap, venous end cap) and blood lines (CombiSet: Arterial chamber, venous chamber; Streamline: Arterial pod, venous pod, venous chamber) for each clotting grade using the visual inspection clotting grade scale |
| Urea Reduction Ratio (URR) for All HD Sessions | Approximately 5 weeks | to assess the adequacy of each dialysis session |
| spKt/V for All HD Sessions | 2 weeks for each period | to assess the dialysis adequacy of each HD session |
| The Reason for Saline Administration Per Subject Per HD Session (Other Than for Circuit Priming or Rinse Back). | Approximately 4.5 hours | to determine if a HD was successful. When saline was used for maintaining blood flow or treating clotting, the heparin free HD was not successful. |
| HD Treatment Duration or Time to Complete Circuit Occlusion (Grade 4) | Approximately 4.5 hours | HD treatment duration or time to complete circuit occlusion (Grade 4). The treatment duration was recorded for each HD session. |
| Blood Volume Processed for Heparin Free | Approximately 4.5 hours for each HD session | Blood volume processed (BVP) for each of 3 heparin free HD sessions (expected). The average of BVPs for each subject was calculated first then the descriptive stat. were derived. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence AB: Circuit A Following by Circuit B Circuit (A) includes the dialyzer with Endexo and the CombiSet bloodline
Dialyzer with Endexo: Sequence AB:
Period 1 Circuit A (Five Visits: 1,2,3,4,5) Period 2 Circuit B (Five Visits: 9,10,11,12,13)
Sequence BA:
Period 1 Circuit B (Five Visits: 1,2,3,4,5) Period 2 Circuit A (Five Visits: 9,10,11,12,13) | 8 |
| Sequence BA: Circuit B Follow by Circuit A Circuit (B) includes dialyzer with Endexo and the Streamline bloodline
Dialyzer with Endexo: Sequence AB:
Period 1 Circuit A (Five Visits: 1,2,3,4,5) Period 2 Circuit B (Five Visits: 9,10,11,12,13)
Sequence BA:
Period 1 Circuit B (Five Visits: 1,2,3,4,5) Period 2 Circuit A (Five Visits: 9,10,11,12,13) | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Sequence BA: Circuit B Follow by Circuit A | Total | Sequence AB: Circuit A Following by Circuit B |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 6.63 | 64.3 years STANDARD_DEVIATION 8.32 | 63.6 years STANDARD_DEVIATION 10.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 2 / 16 | 2 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
The Primary Endpoint is the Number and Percent (%) of Successful Heparin-free HD Sessions for Each Subject in Each Circuit.
Each participant was expected to receive 3 heparin-free HD sessions. The number and percentage of successful HD sessions were derived based on the 3 heparin-free HD sessions for each participant in each circuit. A successful HD session must meet all the following criteria: 1. Absence of complete HD circuit occlusion (Grade 4) rendering dialysis impossible 2. Absence of the need to replace dialyzers or bloodlines due to clotting 3. Absence of saline flushes to maintain blood flow through the circuit during the HD session 4. Absence of any additional heparin beyond what is allowed per study visits 5. Single pool Kt/V (spKt/V) ≥ 1.2
Time frame: Approximately 5 weeks, Period 1: two weeks with either Circuit A or Circuit B; Washout: 1 week; Period 2: two weeks with the circuit other than Period 1.
Population: Analysis population, defined as subjects who signed the ICF, met inclusion criteria, did not meet any exclusion criteria, were enrolled, randomized, and had at least one heparin reduction HD treatment.~Based on the definition of analysis population, there were 15 subjects in Circuit A and 16 subjects in Circuit B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Circuit A | The Primary Endpoint is the Number and Percent (%) of Successful Heparin-free HD Sessions for Each Subject in Each Circuit. | 2.4 number of successful HD sessions | Standard Deviation 1.12 |
| Circuit B | The Primary Endpoint is the Number and Percent (%) of Successful Heparin-free HD Sessions for Each Subject in Each Circuit. | 2.9 number of successful HD sessions | Standard Deviation 0.5 |
Secondary
The Secondary Endpoints Include Adverse Events .
The number of Serious Adverse Events and Adverse Events during the study periods
Time frame: two weeks each period (10 weeks per subject: 4 weeks for screening, 2 weeks for Period 1, 1 week for Washout, and 2 weeks for Period 2)
Population: Safety population, defined as subjects who signed the ICF, met inclusion criteria, did not meet any exclusion criteria, were enrolled, and randomized.~Based on the definition of safety population, there were 16 subjects in Circuit A and 16 subjects in Circuit B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Circuit A | The Secondary Endpoints Include Adverse Events . | 2 events |
| Circuit B | The Secondary Endpoints Include Adverse Events . | 4 events |
Secondary
The Secondary Endpoints Include Device-related Adverse Events.
All device-related serious adverse events and adverse events occurred during the study periods
Time frame: two weeks each period (10 weeks per subject: 4 weeks for screening, 2 weeks for Period 1, 1 week for Washout, and 2 weeks for Period 2)
Population: Safety population, defined as subjects who signed the ICF, met inclusion criteria, did not meet any exclusion criteria, were enrolled, and randomized.~Based on the definition of safety population, there were 16 subjects in Circuit A and 16 subjects in Circuit B.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Circuit A | The Secondary Endpoints Include Device-related Adverse Events. | 0 events |
| Circuit B | The Secondary Endpoints Include Device-related Adverse Events. | 0 events |
Other Pre-specified
Blood Volume Processed for Heparin Free
Blood volume processed (BVP) for each of 3 heparin free HD sessions (expected). The average of BVPs for each subject was calculated first then the descriptive stat. were derived.
Time frame: Approximately 4.5 hours for each HD session
Population: Analysis population, defined as subjects who signed the ICF, met inclusion criteria, did not meet any exclusion criteria, were enrolled, randomized, and had at least one heparin reduction HD treatment.~Based on the definition of analysis population, there were 15 subjects in Circuit A and 16 subjects in Circuit B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Circuit A | Blood Volume Processed for Heparin Free | 88.33 L | Standard Deviation 7.637 |
| Circuit B | Blood Volume Processed for Heparin Free | 92.37 L | Standard Deviation 7.19 |
Other Pre-specified
HD Treatment Duration or Time to Complete Circuit Occlusion (Grade 4)
HD treatment duration or time to complete circuit occlusion (Grade 4). The treatment duration was recorded for each HD session.
Time frame: Approximately 4.5 hours
Other Pre-specified
Number and Percentage of Dialyzers and Blood Lines for Each Clotting Grade Using the Visual Inspection Clotting Grade Scale
Number and percentage of dialyzers (arterial end cap, venous end cap) and blood lines (CombiSet: Arterial chamber, venous chamber; Streamline: Arterial pod, venous pod, venous chamber) for each clotting grade using the visual inspection clotting grade scale
Time frame: Approximately 5 weeks
Other Pre-specified
spKt/V for All HD Sessions
to assess the dialysis adequacy of each HD session
Time frame: 2 weeks for each period
Other Pre-specified
The Reason for Saline Administration Per Subject Per HD Session (Other Than for Circuit Priming or Rinse Back).
to determine if a HD was successful. When saline was used for maintaining blood flow or treating clotting, the heparin free HD was not successful.
Time frame: Approximately 4.5 hours
Other Pre-specified
The Time of Saline Administered Per Subject Per HD Session (Other Than for Circuit Priming or Rinse Back).
The time of saline administered per subject per HD session (other than for circuit priming or rinse back) during a HD session.
Time frame: Approximately 4.5 hours
Other Pre-specified
The Volume of Saline Administered Per Subject Per HD Session (Other Than for Circuit Priming or Rinse Back).
The volume of saline administered per subject per HD session (other than for circuit priming or rinse back). The total volume was calculated for each HD session.
Time frame: Approximately 4.5 hours
Other Pre-specified
Urea Reduction Ratio (URR) for All HD Sessions
to assess the adequacy of each dialysis session
Time frame: Approximately 5 weeks