Early Feasibility Study to Evaluate the Safety and Efficacy of PAK HD in ESRD Patients

Early Feasibility Study to Evaluate the Safety and Efficacy of PAK HD in ESRD Patients

The purpose of this study is to demonstrate the safety of dialysate regeneration of the PAK HD sorbent cartridge and therapy efficacy of the PAK HD sorbent therapy compared with conventional hemodialysis.

This clinical trial is being conducted to evaluate the biochemical safety of dialysate regeneration with the PAK HD sorbent cartridge in a limited number of patients and treatments. Therapy efficacy of the PAK HD sorbent therapy will be compared to conventional hemodialysis under the same therapy settings. The trial will use only one single PAK HD sorbent therapy per patient, and a total of 3 patients. The PAK HD therapies will be performed in the middle of the week.

Inclusion Criteria:

1. Subjects must be adults >/= 21 years old and <80 years old.

2. Subjects must be weighing >/= 55kg and <90kg (patient's dry weight).

3. Subjects must have stable haemoglobin >/= 10.5g/dL, 2 months prior to enrolment

4. Subjects' pre-dialysis serum values must be within the following range, 2 months prior to enrolment:

   Patient allowable serum biochemistry ranges Allowable pre-dialysis serum values Na >/= 132 mmol/L or </= 145mmol/L HCO3 >/= 15mmol/L or </= 30mmol/L K >/= 3.5mmol/L or </= 5.8mmol/L

5. Subjects on stable on thrice weekly 4-h HD schedule. Stability is defined as:

   • Haemodynamic stability during dialysis (absence of hypotensive events and symptomatic arrhythmias), no angina pectoris, AND
   • No altered level of consciousness during dialysis.

6. Subjects with a well-functioning vascular access (native fistula graft):

   • capable of providing a blood flow rate of >/= 250 mL/min, AND
   • no vascular access revision and stable shunt flow for at least 4 weeks prior to enrolment.

7. Subjects capable of understanding the informed consent form and give informed consent.

8. Subjects willing and able to comply with study procedures and to attend all study follow-up visits.

9. Subjects who are female of reproducible age to practice birth control methods.

10. Subjects can be either gender.

Exclusion Criteria:

1. Subjects with haemoglobin level of <10.5g/dL in any measurement 2 months prior to enrolment.

2. Subjects with the following pre-dialysis serum values in any measurement 2 months prior to enrolment:

   • sodium concentration <132 mmol/L or > 145mmol/L
   • bicarbonate <15mmol/L or >30mmol/L
   • plasma potassium concentration <3.5mmol/L or >5.8mmol/L
   • urea <15mmol/L or >28 mmol/L

3. Subjects with severe hypertension: systolic blood pressure > /=180 mmHg, diastolic blood pressure >/=120 mmHg in any officemeasurement less than 4 weeks prior to enrolment.

4. Subjects with chronic obstructive pulmonary disease or any respiratory disease that may predispose to CO2 retention.

5. Subjects with impaired liver function. Impaired liver function is defined as an elevated ALT (alanine aminotransferase) by 3-fold orgreater above the upper limit of normal.

6. Subjects with episodes of haemolysis in any measurement 3 months prior to enrolment.

7. Subjects with a central venous catheter.

8. Subjects with vascular access dysfunction (whether or not requiring an intervention), i.e. failure to achieve and/ or sustain a bloodflow of >/=250 mL/min and/or signs of compromised vascular access patency (according to the opinion of the investigator) within 4weeks prior to enrolment.

9. Subjects with vascular access related infection less than 4 weeks prior to enrolment

10. Subjects requiring an average ultrafiltration volume >2.8 L per 4-h treatment in mid-week dialysis session in the past 4 weeks priorto enrolment.

11. Subjects who are on heparin free dialysis

12. Subjects who are unable to provide informed consent.

13. Subjects who are unable to comply with study procedures.

14. Subjects with psychosocial problems which may negatively influence dialysis treatment.

15. Subjects who participated in another clinical intervention or device trial less than 12 weeks prior to enrolment, are currentlyparticipating or intend to participate in such a trial.

16. Subjects who are pregnant, breast feeding, or planning a pregnancy within the study period.

17. Subjects with a life expectancy <1 year.

18. Subjects who are anticipating a living donor kidney transplantation within < 2 months of the study period.

19. Subjects with recent history of drug and/or alcohol abuse in the last 3 months prior to enrolment.