A Pilot Trial of Twice-weekly Versus Thrice-weekly Hemodialysis in Patients With Incident End-stage Kidney Disease

NCT ID: NCT03740048

Last Updated: 2023-06-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-19

Study Completion Date

2021-11-04

Brief Summary

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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.

Detailed Description

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Conditions

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End Stage Renal Failure on Dialysis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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)

Group Type EXPERIMENTAL

Hemodialysis

Intervention Type OTHER

Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.

Patiromer Oral Product

Intervention Type DRUG

Participants in the intervention group who develop hyperkalemia, during the first six weeks of receiving hemodialysis twice per week, will be treated with Patiromer.

Conventional Hemodialysis Regimen

Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis

Group Type ACTIVE_COMPARATOR

Hemodialysis

Intervention Type OTHER

Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.

Interventions

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Hemodialysis

Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.

Intervention Type OTHER

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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Wake Forest University Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mariana Murea, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

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Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Countries

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United States

References

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National Kidney Foundation. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 update. Am J Kidney Dis. 2015 Nov;66(5):884-930. doi: 10.1053/j.ajkd.2015.07.015.

Reference Type BACKGROUND
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Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription on patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med. 1981 Nov 12;305(20):1176-81. doi: 10.1056/NEJM198111123052003.

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Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto R; Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002 Dec 19;347(25):2010-9. doi: 10.1056/NEJMoa021583.

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Chin AI, Appasamy S, Carey RJ, Madan N. Feasibility of Incremental 2-Times Weekly Hemodialysis in Incident Patients With Residual Kidney Function. Kidney Int Rep. 2017 Jun 21;2(5):933-942. doi: 10.1016/j.ekir.2017.06.005. eCollection 2017 Sep.

Reference Type BACKGROUND
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Lin YF, Huang JW, Wu MS, Chu TS, Lin SL, Chen YM, Tsai TJ, Wu KD. Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis. Nephrology (Carlton). 2009 Feb;14(1):59-64. doi: 10.1111/j.1440-1797.2008.01016.x. Epub 2008 Nov 19.

Reference Type BACKGROUND
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Zhang M, Wang M, Li H, Yu P, Yuan L, Hao C, Chen J, Kalantar-Zadeh K. Association of initial twice-weekly hemodialysis treatment with preservation of residual kidney function in ESRD patients. Am J Nephrol. 2014;40(2):140-50. doi: 10.1159/000365819. Epub 2014 Aug 23.

Reference Type BACKGROUND
PMID: 25171342 (View on PubMed)

Shafi T, Jaar BG, Plantinga LC, Fink NE, Sadler JH, Parekh RS, Powe NR, Coresh J. Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis. 2010 Aug;56(2):348-58. doi: 10.1053/j.ajkd.2010.03.020. Epub 2010 Jun 3.

Reference Type BACKGROUND
PMID: 20605303 (View on PubMed)

Termorshuizen F, Dekker FW, van Manen JG, Korevaar JC, Boeschoten EW, Krediet RT; NECOSAD Study Group. Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol. 2004 Apr;15(4):1061-70. doi: 10.1097/01.asn.0000117976.29592.93.

Reference Type BACKGROUND
PMID: 15034110 (View on PubMed)

Marquez IO, Tambra S, Luo FY, Li Y, Plummer NS, Hostetter TH, Meyer TW. Contribution of residual function to removal of protein-bound solutes in hemodialysis. Clin J Am Soc Nephrol. 2011 Feb;6(2):290-6. doi: 10.2215/CJN.06100710. Epub 2010 Oct 28.

Reference Type BACKGROUND
PMID: 21030575 (View on PubMed)

Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, Wittes J, Christ-Schmidt H, Berman L, Pitt B; OPAL-HK Investigators. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015 Jan 15;372(3):211-21. doi: 10.1056/NEJMoa1410853. Epub 2014 Nov 21.

Reference Type BACKGROUND
PMID: 25415805 (View on PubMed)

Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, Stasiv Y, Zawadzki R, Berman L, Bushinsky DA; AMETHYST-DN Investigators. Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial. JAMA. 2015 Jul 14;314(2):151-61. doi: 10.1001/jama.2015.7446.

Reference Type BACKGROUND
PMID: 26172895 (View on PubMed)

Pitt B, Bakris GL, Bushinsky DA, Garza D, Mayo MR, Stasiv Y, Christ-Schmidt H, Berman L, Weir MR. Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors. Eur J Heart Fail. 2015 Oct;17(10):1057-65. doi: 10.1002/ejhf.402. Epub 2015 Oct 12.

Reference Type BACKGROUND
PMID: 26459796 (View on PubMed)

Kovesdy CP, Regidor DL, Mehrotra R, Jing J, McAllister CJ, Greenland S, Kopple JD, Kalantar-Zadeh K. Serum and dialysate potassium concentrations and survival in hemodialysis patients. Clin J Am Soc Nephrol. 2007 Sep;2(5):999-1007. doi: 10.2215/CJN.04451206. Epub 2007 Aug 16.

Reference Type BACKGROUND
PMID: 17702709 (View on PubMed)

Wu DY, Shinaberger CS, Regidor DL, McAllister CJ, Kopple JD, Kalantar-Zadeh K. Association between serum bicarbonate and death in hemodialysis patients: is it better to be acidotic or alkalotic? Clin J Am Soc Nephrol. 2006 Jan;1(1):70-8. doi: 10.2215/CJN.00010505. Epub 2005 Nov 23.

Reference Type BACKGROUND
PMID: 17699193 (View on PubMed)

Daugirdas JT. Estimating Time-averaged Serum Urea Nitrogen Concentration during Various Urine Collection Periods: A Prediction Equation for Thrice Weekly and Biweekly Dialysis Schedules. Semin Dial. 2016 Nov;29(6):507-509. doi: 10.1111/sdi.12554. Epub 2016 Oct 4.

Reference Type BACKGROUND
PMID: 27699876 (View on PubMed)

Daugirdas JT, Depner TA, Greene T, Levin NW, Chertow GM, Rocco MV; Frequent Hemodialysis Network Trial Group. Standard Kt/Vurea: a method of calculation that includes effects of fluid removal and residual kidney clearance. Kidney Int. 2010 Apr;77(7):637-44. doi: 10.1038/ki.2009.525. Epub 2010 Jan 27.

Reference Type BACKGROUND
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Jansen MA, Hart AA, Korevaar JC, Dekker FW, Boeschoten EW, Krediet RT; NECOSAD Study Group. Predictors of the rate of decline of residual renal function in incident dialysis patients. Kidney Int. 2002 Sep;62(3):1046-53. doi: 10.1046/j.1523-1755.2002.00505.x.

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Murea M, Highland BR, Yang W, Dressler E, Russell GB. Patient-reported outcomes in a pilot clinical trial of twice-weekly hemodialysis start with adjuvant pharmacotherapy and transition to thrice-weekly hemodialysis vs conventional hemodialysis. BMC Nephrol. 2022 Sep 27;23(1):322. doi: 10.1186/s12882-022-02946-w.

Reference Type DERIVED
PMID: 36167537 (View on PubMed)

Murea M, Patel A, Highland BR, Yang W, Fletcher AJ, Kalantar-Zadeh K, Dressler E, Russell GB. Twice-Weekly Hemodialysis With Adjuvant Pharmacotherapy and Transition to Thrice-Weekly Hemodialysis: A Pilot Study. Am J Kidney Dis. 2022 Aug;80(2):227-240.e1. doi: 10.1053/j.ajkd.2021.12.001. Epub 2021 Dec 18.

Reference Type DERIVED
PMID: 34933066 (View on PubMed)

Murea M, Moossavi S, Fletcher AJ, Jones DN, Sheikh HI, Russell G, Kalantar-Zadeh K. Renal replacement treatment initiation with twice-weekly versus thrice-weekly haemodialysis in patients with incident dialysis-dependent kidney disease: rationale and design of the TWOPLUS pilot clinical trial. BMJ Open. 2021 May 24;11(5):e047596. doi: 10.1136/bmjopen-2020-047596.

Reference Type DERIVED
PMID: 34031117 (View on PubMed)

Murea M. Precision medicine approach to dialysis including incremental and decremental dialysis regimens. Curr Opin Nephrol Hypertens. 2021 Jan;30(1):85-92. doi: 10.1097/MNH.0000000000000667.

Reference Type DERIVED
PMID: 33165001 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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IRB00054726

Identifier Type: -

Identifier Source: org_study_id

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