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

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ClinicalTrials.gov Identifier: NCT03740048
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Study Description
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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.

Condition or disease Intervention/treatment Phase
End Stage Renal Failure on Dialysis Other: Hemodialysis Drug: Patiromer Oral Product Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Pilot Study of Hemodialysis Initiation Comparing Twice-Weekly Hemodialysis Plus Dialysis-Sparing Therapy Versus Thrice-Weekly Hemodialysis (The TWOPLUS-HD Trial)
Actual Study Start Date : June 19, 2019
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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)
 Other: Hemodialysis
Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.

Drug: 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.
Active Comparator: Conventional Hemodialysis Regimen
Hemodialysis regimen at the initiation of dialysis treatment: thrice-weekly hemodialysis
 Other: Hemodialysis
Hemodialysis frequency will differ in the first six weeks of hemodialysis therapy between the two treatment arms.


Outcome Measures
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Primary Outcome Measures :
  1. Recruitment rate [ Time Frame: up to 24 months ]
    Feasibility will be determined based on the recruitment rate, assessed as the proportion of people meeting inclusion criteria who ultimately consent to randomization.

  2. Protocol adherence rate [ Time Frame: up to 24 months ]
    Feasibility will be determined based on protocol adherence rate, assessed as the proportion of participants who abide to the HD schedule, including transition from twice-weekly to thrice-weekly HD.

  3. Incidence rate of severe adverse events related to the intervention of stepped hemodialysis [ Time Frame: day 1 to day 90 after randomization ]
    Safety of the intervention will be assessed based on the incidence rate of severe adverse events related to the intervention in the first 3 months after randomization


Secondary Outcome Measures :
  1. Change in residual kidney function [ Time Frame: up to 24 months ]
    Residual renal urea clearance (Krt/Vurea) will be calculated at baseline and after HD initiation (week 6 and week 12) as clearance per minute excretion of urea nitrogen using time-averaged serum water urea nitrogen concentration during the urine collection period.

  2. Events of hyperkalemia [ Time Frame: up to 24 months ]
    The rate of hyperkalemia events (serum potassium ≥5.5mEq/L on inter-dialytic day or ≥6.0mEq/L pre-HD on dialysis day) in the first 12 weeks of hemodialysis will be compared between the two study groups.

  3. Volume Management [ Time Frame: up to 24 months ]
    Volume management will be compared between study groups as proportion of markers of volume overload in the first 12 weeks of hemodialysis. Surrogate markers of volume overload will include: inter-dialytic weight gain >2.5kg, relative inter-dialytic weight gain >5.7% of the target weight, and ultrafiltration rate >10ml/kg/hr.

  4. Solute clearance [ Time Frame: up to 24 months ]
    Monthly spKt/Vurea and stdKt/Vurea in the first quarter of hemodialysis will be compared between the two treatment groups. Total stdKt/Vurea will be calculated by adding residual renal urea clearance (Krt/Vurea ) (i.e., stdKt/Vurea month 1 will include baseline Krt/Vurea; stdKt/Vurea month 2 will include Krt/Vurea based on inter-dialytic urine collection performed during week 6; stdKt/Vurea month 3 will include Krt/Vurea performed during week 12).

  5. Events of metabolic acidosis [ Time Frame: up to 24 months ]
    Metabolic acidosis will be classified as serum bicarbonate ≤22mEq/L on inter-dialytic day or ≤20mEq/L pre-HD on dialysis day. The rate of metabolic acidosis in the first 12 weeks of hemodialysis will be compared between the two study groups.

  6. Hospitalization Rate [ Time Frame: up to 24 months ]
    The hospitalization rate will be compared in the first 12 weeks of hemodialysis between the two treatment groups and expressed per 100 patient-days.


Other Outcome Measures:
  1. 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.

  2. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03740048


Contacts
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Contact: Carrie Smith 3367137531 suscmit@wakehealth.edu
Contact: Mariana Murea, MD 3367162074 mmurea@wakehealth.edu

Locations
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United States, North Carolina
Wake Forest Baptist Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Carrie Smith    336-713-7531    suscmit@wakehealth.edu   
Contact: Mariana Murea, MD    3367162074    mmurea@wakehealth.edu   
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
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Principal Investigator: Mariana Murea, MD Wake Forest University Health Sciences
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03740048    
Other Study ID Numbers: IRB00054726
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: June 24, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 2-4 months

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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
Keywords provided by Wake Forest University Health Sciences:
Hemodialysis
Kidney Disease
Kidney Function
Additional relevant MeSH terms:
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Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency
Renal Insufficiency, Chronic