Diuretic/Cool Dialysate Trial

Study Overview
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Brief Summary
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The proposed pilot study challenges the current widespread paradigm of discontinuing loop diuretics when initiating chronic HD and/or maintaining the dialysate at a constant temperature of 37 °C for all patients.

Detailed Description
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This pilot/feasibility RCT will recruit for 18 months and demonstrate the feasibility and safety of performing a large scale study of diuretic use and/or cool dialysate examining recruitment, retention, and key outcomes. This study will further assess whether the use of a diuretic compared to non-use of a diuretic and/or the use of cool dialysate (35.5 ºC) compared to 37 ºC for up to 6 months will improve residual renal function (RRF), improve health reported quality of life (HRQOL) and reduce hospitalizations by randomizing 20 dialysis-naïve patients (started chronic HD in the last three months) from DCI centers in the greater Albuquerque area, to either bumetanide and cool dialysate randomized in a two-by-two factorial distribution.

Official Title
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Diuretic/Cool Dialysate Trial

Conditions
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Chronic Kidney Insufficiency

Intervention / Treatment
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* Drug: Bumetanide
* Other: Cool Dialysate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary speaking language is English. Patient is HD naïve (Patient may still enroll as long as no more than 12 weeks of in-center HD have been performed prior to randomization) HD takes place at one of the participating Dialysis Clinic Inc. (DCI) sites during the data collection period. Daily urine output is over 500ml. Patients must be willing and able to sign the consent form. Exclusion Criteria: RRF <5 mL/min/1.73 m2 as determined by iohexol GFR measurement. Allergy or contraindication to iohexol and/or bumetanide. Has been undergoing dialysis for more than 12 weeks. Expectation that native kidneys will recover. History of poor adherence to treatment. Unable to verbally communicate in English. Requires more than 3 HD treatments per week due to medical co-morbidity (such as, but not limited to: severe volume overload requiring frequent HD e.g. in systemic oxalosis, or requiring total parenteral nutrition). Scheduled for living donor kidney transplant in the next 6 months. Intention to change to peritoneal dialysis, or home HD in the next 6 months. Plan to relocate to another center within the next 7-8 months. Expected geographic unavailability at a participating HD unit for >2 consecutive weeks or >4 weeks total during the next 6 months (excluding unavailability due to hospitalizations) Post kidney transplantation Currently in an acute or chronic care hospital Life expectancy <6 months or intention to withdraw dialysis therapy within 6 months. Current pregnancy Actively planning to become pregnant in the next 8 months Nursing mothers Current use of investigational drugs Participation in another non-observational clinical trial that contradicts or interferes with the therapies or measured outcomes in this trial Unable or unwilling to follow the study protocol for any reason (including mental incompetence) Unable or unwilling to provide informed consent or sign IRB-approved consent form. The following special populations will not be included in this study: Patients who are too infirm or lack the capacity to meaningfully participate in medical decisions and to sign the informed consent. Children and adolescents constitute <2% of the dialysis population, and our preliminary survey of the study sites found no children and adolescents were active patients. In any case, the renal and other physical factors of children and adolescents with ESRD are not directly comparable to those of adults. Prisoners.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No Diuretic and 37°C dialysate<br>Standard of care, no diuretic | |
| Experimental: No Diuretic and 35.5°C dialysate<br>Cool dialysate only, no diuretic | Other: Cool Dialysate<br>* Cool dialysate (35°C)<br>|
| Experimental: Diuretic and 37°C dialysate<br>Isothermic dialysate (37°C) and bumetanide (diuretic) | Drug: Bumetanide<br>* Diuretic<br>* Other names: Bumex;|
| Experimental: Diuretic and 35.5°C dialysate<br>Cool dialysate (35.5°C) and bumetanide (diuretic) | Drug: Bumetanide<br>* Diuretic<br>* Other names: Bumex;Other: Cool Dialysate<br>* Cool dialysate (35°C)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in residual kidney function over 6 months |  | 6 months | 
| Association of HD frequency with inflammation | Blood and urine labs: CRP, IL-6, IL-1β, TNF-α, β2M, micro-RNA, albumin and urinary micro-RNA, respectively, will be reviewed in association with their collective relationship to indications of HD frequency with inflammation. | 6 months | 
| Acute Kidney Injury (AKI) markers | Blood and urine labs: β2Μ, cystatin C, creatinine, micro-RNA, NGAL, KIM-1 and urinary NGAL, urinary KIM-1, urinary HGF, micro-RNA, cystatin C, creatinine, respectively, will be reviewed in association with their collective relationship to indications of acute kidney injury. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in health reported quality of life (HRQOL) within the first six months | Changes in physical, mental, emotional, fatigue and social well-being symptoms will be monitored through the Dialysis Symtoms Index and PROMIS-57 questionnaires | 6 months | 
| Time to first non-access hospitalization |  | 6 months |