Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03740048
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 202 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 : June 2020
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


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.




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

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

  3. 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.


Secondary Outcome Measures :
  1. 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).

  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. 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.

  5. Time to first hospitalization [ Time Frame: up to 24 months ]
    Time to first hospitalization (in days) from first outpatient HD treatment will compared between treatment 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.

  7. Assessment of Quality of Life- KDQOL-SF36 questionnaire [ Time Frame: up to 24 months ]
    The Kidney Disease Quality of Life (KDQOL-SF36) questionnaire is a short form that measures the burden of kidney disease, symptoms/problems of kidney disease, and effects of kidney disease scales. The score range is 0-100 with higher scores denoting better outcomes.


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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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)
  • Were previously on other types of RRT
  • 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.

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
Layout table for location contacts
Contact: Carrie Smith 3367137531 suscmit@wakehealth.edu
Contact: Mariana Murea, MD 3367162074 mmurea@wakehealth.edu

Locations
Layout table for location information
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
Layout table for investigator information
Principal Investigator: Mariana Murea, MD Wake Forest University Health Sciences

Publications:

Layout table for additonal information
Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03740048     History of Changes
Other Study ID Numbers: IRB00054726
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: June 24, 2019
Last Verified: May 2019
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

Layout table for additional information
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:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic