- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03740048
A Pilot Trial of Twice-weekly Versus Thrice-weekly Hemodialysis in Patients With Incident End-stage Kidney Disease (TWOPLUS-HD)
June 7, 2023 updated by: Wake Forest University Health Sciences
A Randomized Pilot Study of Hemodialysis Initiation Comparing Twice-Weekly Hemodialysis Plus Dialysis-Sparing Therapy Versus Thrice-Weekly Hemodialysis (The TWOPLUS-HD Trial)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
51
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Carrie Smith
- Phone Number: 3367137531
- Email: suscmit@wakehealth.edu
Study Contact Backup
- Name: Mariana Murea, MD
- Phone Number: 3367162074
- Email: mmurea@wakehealth.edu
Study Locations
-
-
North Carolina
-
Winston-Salem, North Carolina, United States, 27157
- Wake Forest Baptist Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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 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.
|
Active Comparator: Conventional Hemodialysis Regimen
Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis
|
Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patients' Adherence to Study Protocol
Time Frame: 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
|
6 months, 12 months, 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
24-hour Urine Volume
Time Frame: 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
|
Baseline, 6 Weeks, 12 Weeks, 24 Weeks
|
Change in Residual Kidney Function - Urea Clearance
Time Frame: 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.
|
Baseline, 6 Weeks, 12 Weeks, 24 Weeks
|
Change in Residual Kidney Function - Creatinine Clearance
Time Frame: 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.
|
Baseline, 6 Weeks, 12 Weeks, 24 Weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Long-term change in residual kidney function
Time Frame: up to 24 months
|
Residual renal urea clearance (Krt/Vurea) will be calculated based on inter-dialytic urine collection at week 24 and week 48 of hemodialysis.
The change in Krt/Vurea from baseline will be compared between the two treatment arms.
|
up to 24 months
|
Survival
Time Frame: up to 24 months
|
Exploratory analyses will compare the mortality rate between the two schedules of hemodialysis at week 12, week 24 and week 48 after dialysis initiation.
|
up to 24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Mariana Murea, MD, Wake Forest University Health Sciences
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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. Erratum In: Am J Kidney Dis. 2016 Mar;67(3):534.
- 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.
- 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.
- 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.
- 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. Erratum In: JAMA. 2015 Aug 18;314(7):731. Dosage error in article text.
- 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.
- Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription of patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med. 1981 Nov 12;305(20):1176-81. doi: 10.1056/NEJM198111123052003.
- Paniagua R, Amato D, Vonesh E, Correa-Rotter R, Ramos A, Moran J, Mujais S. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol. 2002 May;13(5):1307-1320. doi: 10.1681/ASN.V1351307.
- Lo WK, Ho YW, Li CS, Wong KS, Chan TM, Yu AW, Ng FS, Cheng IK. Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study. Kidney Int. 2003 Aug;64(2):649-56. doi: 10.1046/j.1523-1755.2003.00098.x.
- Li Y, Jin Y, Kapke A, Pearson J, Saran R, Port FK, Robinson BM. Explaining trends and variation in timing of dialysis initiation in the United States. Medicine (Baltimore). 2017 May;96(20):e6911. doi: 10.1097/MD.0000000000006911.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 19, 2019
Primary Completion (Actual)
November 4, 2021
Study Completion (Actual)
November 4, 2021
Study Registration Dates
First Submitted
November 9, 2018
First Submitted That Met QC Criteria
November 9, 2018
First Posted (Actual)
November 14, 2018
Study Record Updates
Last Update Posted (Actual)
June 9, 2023
Last Update Submitted That Met QC Criteria
June 7, 2023
Last Verified
April 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00054726
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
After study completion, de-identified participant data may be provided to other researchers in the filed if requested.
The request(s) will be reviewed by the principal investigator and other study members to determine if appropriate.
IPD Sharing Time Frame
2-4 months
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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