End Stage Renal Failure on Dialysis
Conditions
Keywords
Hemodialysis, Kidney Disease, Kidney Function
Brief summary
The optimal frequency of hemodialysis treatments in patients with incident end-stage kidney disease in not known. This pilot trial will randomize patients with incident end-stage kidney disease due to chronic kidney disease progression to two different regimens of hemodialysis: i) twice-weekly hemodialysis for six weeks with adjuvant pharmacologic medications followed by thrice-weekly hemodialysis, or ii) thrice-weekly hemodialysis. The study will test feasibility of stepwise hemodialysis, and the effects of the two regimens of hemodialysis on residual kidney function.
Interventions
OTHERHemodialysis
Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.
Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age ≥18 years * Incident ESKD from CKD progression (including a failing renal transplant) * Are deemed to require dialysis initiation by the treating nephrologist * Have elected HD for renal replacement therapy (RRT)
Exclusion criteria
* Have urine output \<500ml per day * Have ESKD as a result of severe acute kidney injury (AKI) (stage 3 AKI defined by Acute Kidney Injury Network \[AKIN\]) criteria) * Abrupt decline in kidney function preceding HD therapy initiation (i.e., if eGFR was ≥30 mL/min/1.73 m2 3 months prior to the initiation of dialysis therapy) * Are scheduled to undergo transplantation from a live donor within the next 6 months * Have an active diagnosis of hepatorenal syndrome * Have a significant malignancy that is likely to impact survival * Have a medical condition that would jeopardize the safety of the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients' Adherence to Study Protocol | 6 months, 12 months, 24 months | ≥95% of participants randomized in the intervention group will adhere to the HD regimen. All participants who completed 6 and 12 months of follow-up completed interdialytic timed urine collections - Patient adherence to the study protocol was assessed by the number of participants randomized to each intervention who adhered to the study protocol and at 6 months and at 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Urine Volume | Baseline, 6 Weeks, 12 Weeks, 24 Weeks | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed at baseline, 6 Weeks, 12 Weeks and 24 Weeks |
| Change in Residual Kidney Function - Urea Clearance | Baseline, 6 Weeks, 12 Weeks, 24 Weeks | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. |
| Change in Residual Kidney Function - Creatinine Clearance | Baseline, 6 Weeks, 12 Weeks, 24 Weeks | Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24. |
Countries
United States
Participant flow
Recruitment details
51 patients consented to participate and enrolled for the study. 48 patients were randomized to treatment with twice-weekly HD and adjuvant pharmacotherapy for 6 weeks followed by thrice-weekly HD (n = 23) or continued usual care treatment with thrice-weekly HD (n = 25).
Pre-assignment details
77 patients (41%) were approached for study participation. Of those, 51 (66%) consented to participate, resulting in 48 patients randomized to treatment with twice-weekly HD and adjuvant pharmacotherapy for 6 weeks followed by thrice-weekly HD (n = 23) or continued usual care treatment with thrice-weekly HD (n = 25).
Participants by arm
| Arm | Count |
|---|---|
| Hemodialysis and Pharmacologic Therapy Hemodialysis regimen at the initiation of dialysis treatment: Twice-weekly hemodialysis plus adjunctive pharmacologic therapy (loop diuretic, potassium-binding agent, and sodium bicarbonate) for six consecutive weeks, continued by thrice-weekly hemodialysis (intervention group)
Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.
Patiromer Oral Product: Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer. | 23 |
| Conventional Hemodialysis Regimen Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis
Hemodialysis: Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms. | 25 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 6 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Non-compliance with HD | 0 | 1 |
| Overall Study | Switched to Peritoneal Dialysis | 2 | 0 |
| Overall Study | Switched to thrice-weekly HD | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Hemodialysis and Pharmacologic Therapy | Conventional Hemodialysis Regimen | Total |
|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 15 | 63.3 years STANDARD_DEVIATION 12.8 | 61.3 years STANDARD_DEVIATION 14 |
| Body mass index | 32.5 kg/m^2 STANDARD_DEVIATION 9.4 | 31.8 kg/m^2 STANDARD_DEVIATION 8.4 | 32.1 kg/m^2 STANDARD_DEVIATION 8.8 |
| Body surface area | 2.1 m^2 STANDARD_DEVIATION 0.2 | 2.0 m^2 STANDARD_DEVIATION 0.3 | 2.06 m^2 STANDARD_DEVIATION 0.3 |
| 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 | 11 Participants | 16 Participants | 27 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 | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 22 | 6 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 11 / 22 | 12 / 22 |
Outcome results
Primary
Patients' Adherence to Study Protocol
≥95% of participants randomized in the intervention group will adhere to the HD regimen. All participants who completed 6 and 12 months of follow-up completed interdialytic timed urine collections - Patient adherence to the study protocol was assessed by the number of participants randomized to each intervention who adhered to the study protocol and at 6 months and at 12 months
Time frame: 6 months, 12 months, 24 months
Population: Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hemodialysis and Pharmacologic Therapy | Patients' Adherence to Study Protocol | Patients adherence to study protocol | 22 Participants |
| Hemodialysis and Pharmacologic Therapy | Patients' Adherence to Study Protocol | interdialytic timed urine collections at 6 month followup | 19 Participants |
| Hemodialysis and Pharmacologic Therapy | Patients' Adherence to Study Protocol | interdialytic timed urine collections at 12 month followup | 10 Participants |
| Conventional Hemodialysis Regimen | Patients' Adherence to Study Protocol | Patients adherence to study protocol | 24 Participants |
| Conventional Hemodialysis Regimen | Patients' Adherence to Study Protocol | interdialytic timed urine collections at 6 month followup | 19 Participants |
| Conventional Hemodialysis Regimen | Patients' Adherence to Study Protocol | interdialytic timed urine collections at 12 month followup | 10 Participants |
Secondary
24-hour Urine Volume
Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed at baseline, 6 Weeks, 12 Weeks and 24 Weeks
Time frame: Baseline, 6 Weeks, 12 Weeks, 24 Weeks
Population: Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Hemodialysis and Pharmacologic Therapy | 24-hour Urine Volume | Urine volume at Baseline | 914 mL/day |
| Hemodialysis and Pharmacologic Therapy | 24-hour Urine Volume | Urine volume at Week 6 | 504 mL/day |
| Hemodialysis and Pharmacologic Therapy | 24-hour Urine Volume | Urine volume at 12 weeks | 479 mL/day |
| Hemodialysis and Pharmacologic Therapy | 24-hour Urine Volume | Urine volume at 24 Weeks | 862 mL/day |
| Conventional Hemodialysis Regimen | 24-hour Urine Volume | Urine volume at 24 Weeks | 876 mL/day |
| Conventional Hemodialysis Regimen | 24-hour Urine Volume | Urine volume at Baseline | 1424 mL/day |
| Conventional Hemodialysis Regimen | 24-hour Urine Volume | Urine volume at 12 weeks | 484 mL/day |
| Conventional Hemodialysis Regimen | 24-hour Urine Volume | Urine volume at Week 6 | 553 mL/day |
Secondary
Change in Residual Kidney Function - Creatinine Clearance
Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24.
Time frame: Baseline, 6 Weeks, 12 Weeks, 24 Weeks
Population: Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Creatinine Clearance | Baseline Renal Creatinine Clearance | 8.4 mL/min/1.73m^2 |
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Creatinine Clearance | Week 6 Renal Creatinine Clearance | 5.5 mL/min/1.73m^2 |
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Creatinine Clearance | Week 12 Renal Creatinine Clearance | 5.3 mL/min/1.73m^2 |
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Creatinine Clearance | Week 24 Renal Creatinine Clearance | 5.6 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Creatinine Clearance | Week 24 Renal Creatinine Clearance | 5.4 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Creatinine Clearance | Baseline Renal Creatinine Clearance | 10.8 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Creatinine Clearance | Week 12 Renal Creatinine Clearance | 5.8 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Creatinine Clearance | Week 6 Renal Creatinine Clearance | 6.8 mL/min/1.73m^2 |
Secondary
Change in Residual Kidney Function - Urea Clearance
Residual renal clearance was calculated based on 24-hour urine collection performed at baseline at enrollment; and interdialytic urine collection performed during weeks 6, 12, and 24.
Time frame: Baseline, 6 Weeks, 12 Weeks, 24 Weeks
Population: Participants were censored at death, HD withdrawal, or conversion to peritoneal dialysis. Not included in data analysis were participants who withdrew consent, were withdrawn from the study because of nonadherence to HD treatments, or were lost to follow-up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Urea Clearance | Baseline Renal Urea Clearance | 3.3 mL/min/1.73m^2 |
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Urea Clearance | Week 6 Renal Urea Clearance | 2.3 mL/min/1.73m^2 |
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Urea Clearance | Week 12 Renal Urea Clearance | 2.1 mL/min/1.73m^2 |
| Hemodialysis and Pharmacologic Therapy | Change in Residual Kidney Function - Urea Clearance | Week 24 Renal Urea Clearance | 1.6 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Urea Clearance | Week 24 Renal Urea Clearance | 2.2 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Urea Clearance | Baseline Renal Urea Clearance | 4.1 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Urea Clearance | Week 12 Renal Urea Clearance | 2.0 mL/min/1.73m^2 |
| Conventional Hemodialysis Regimen | Change in Residual Kidney Function - Urea Clearance | Week 6 Renal Urea Clearance | 2.3 mL/min/1.73m^2 |