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.

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.

Approximately 2 weeks for each period (10 weeks per subject: 4 weeks for screening period, 2 weeks for Period 1, 1 week for Washout, 2 weeks for Period 2)