Dialysate Sodium Lowering Trial

Study Overview
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Brief Summary
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This is a pilot randomized clinical trial in which patients treated with 3X per weekly conventional hemodialysis will be treated to a dialysate sodium 135 mEq/L vs. 138 mEq/L and followed for safety and tolerability, effects on BP and volume.

Detailed Description
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This is a pilot randomized clinical trial in which hypertensive hemodialysis patients will be randomized to a low dialysate sodium (Na) of 135 mEq/L or a standard dialysate Na of 138 mEq/L. Patients will be randomized 2:1 to the low arm. Dialysate Na will be lowered 1 mEq/L every 2 weeks, as tolerated. Tolerance will be assessed by symptoms, intradialytic hypotension (IDH) episodes (systolic BP <90 or intervention for symptoms or BP drop during dialysis), achievement of dry weight. The trial will last for 6 to 12 months, for an individual, depending on when they entered the trial. The primary outcome is feasibility and safety of using the lower dialysate sodium which is assessed by symptoms during or immediately after dialysis, intradialytic hypotension episodes and the frequency of emergency room visits and hospitalizations. Several secondary outcomes will be measured including blood pressure prior to dialysis and at home, change in plasma Na over time, dry weight, post-dialysis weight, interdialytic weight change, symptoms of thirst and dry mouth, self-reported dialysis recovery time, relative blood volume change during a single treatment (via 'Critline') and, in patients without an implanted electronic device, extraceullular fluid volume (via bioimpedance).

Official Title
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Dialysate Sodium Lowering Trial

Conditions
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Hemodialysis Complication, Fluid Overload, Dialysis Disequilibrium, Intra-dialytic Hypotension, Hypertension

Intervention / Treatment
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* Other: Dialysate Sodium Lowering


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Patients undergoing thrice weekly in-center conventional HD At least 90 days since start of hemodialysis Absence of pulmonary edema / signs of fluid overload on physical exam Currently dialyzing at a DNa >=137 mEq/L Single session Kt/V >=1.3 each month for the past 2 months Hypertensive, defined by a pre-dialysis BP of >140/90 or treatment with 1 or more antihypertensive agents No more than 1 skipped treatment and no more than 1 session per month shortened by >10 min Life expectancy >12 months Able to provide Informed Consent Speaks and understands English Exclusion Criteria: Prone to IDH, defined as IDH occurring in >10% of treatments in the past 3 months. IDH will be defined as symptoms (e.g. cramps, dizziness, loss of consciousness) and/or intra- or post-dialytic systolic BP <90 mm Hg and/or use of intervention(s) (UF goal lowered, treatment stopped early, or saline given) because of IDH Pregnancy

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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br> | |
| Experimental: Intervention Group<br>Intervention group will dialyze with dialysate Na 135 mEq/L. | Other: Dialysate Sodium Lowering<br>* Dialysate sodium is lowered until nadir sodium level is reached. Participant dialyzes at this sodium level until end of follow-up.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Intradialytic Hypotension | IDH is determined by review of blood pressures (measured every 30 minutes during dialysis), symptoms (recorded by the nurse during the dialysis treatment and reviewed at Q2 weekly face to face visits by the study team) and the need for intervention (targeted ultrafiltration goal was reduced; treatment was terminated early or saline given for intradialytic hypotension. IDH is defined by any 1 (or more of the following) 1) lowest intradialytic Systolic BP <90 mm Hg or 2) intradialytic symptoms (cramps, lightheadedness, nausea +/-vomiting, diaphoresis, loss of consciousness or seizure) OR 3) intervention performed for symptoms of IDH or lowest intradialytic BP <90 mm Hg. The # IDH events (meeting 1 or more of the 3 criteria above) per 100 treatments will be compared across treatment arms. | Baseline period through study completion, an average of 6 months | 
| Dialysis Dysequilibrium (Safety) | Ascertained via self-report on a questionnaire that asks about the frequency of symptoms suggestive of DD occurring during or immediately after dialysis. The symptoms are: headache, nausea +/- vomiting, confusion, drowsiness, muscle twitching, blurred vision. There are 5 response options ranging from never through to very often for each question. The questionnaire is administered at baseline, at 6 weeks, and Q3 months thereafter. The change in frequency of each symptom will be compared across arms. | Baseline period through study completion, an average of 6 months | 
| Frequency of ER visits and hospitalizations (safety) | The frequency of ER visits and hospitalizations will be ascertained at Q2 weekly study visits. The # of events per time at risk will be compared across treatment arms. | Baseline through study completion | 
| Frequency of patients treated to a dialysate Na 135 mEq/L at end of study (feasibility) | Among those assigned to Dialysate Na 135 mEq/l as the denominator, the # actually continuing to dialyze at this level during the last two weeks of study follow-up. | Last 2 weeks of Follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre- and post-dialysis Plasma Sodium | Taken from lab draws immediately before and after start of dialysis treatment. | Baseline period through study completion, an average of 6 months | 
| Dialysate Sodium | Sample of dialysate sodium taken 30 minutes after start of dialysis treatment. | Baseline period through study completion, an average of 6 months | 
| Relative Blood Volume | Determined using CRIT LINE III monitors. | Baseline period through study completion, an average of 6 months | 
| Bioimpedance Analysis | Water volume and bioimpedance results will be determined using InBodyS10 device. | Baseline period through study completion, an average of 6 months | 
| Interdialytic Weight Gain | Determined by analysis of treatment sheets. | Baseline period through study completion, an average of 6 months | 
| Post Dialysis Weight | Determined by analysis of treatment sheets. | Baseline period through study completion, an average of 6 months | 
| Estimated Dry Weight | Determined by analysis of treatment sheets. | Baseline period through study completion, an average of 6 months | 
| Pre- and Post-dialysis Sitting Blood Pressure | Determined by analysis of treatment sheets. | Baseline period through study completion, an average of 6 months | 
| Home Blood Pressure Monitoring | Participants will use a LifeSource blood pressure monitor to measure their blood pressure weekly at home. | Baseline period through study completion, an average of 6 months | 
| Sodium Loss during Dialysis | Calculated according to the formula: pre-dialysis total body Na - post-dialysis total body Na, where the volume of distribution in the extracellular space is estimated as 0.58*target weight. | Baseline period through study completion, an average of 6 months | 
| Thirst and Xerostomia | Thirst and Xerostomia will be measured via validated, self-administered questionnaires, the 'Dialysis Thirst Inventory' and the 'Xerostomia Inventory' , respectively (BotsCP et al, Kidney International:66; 2004). Change in each inventory score from baseline to the end of the study will be compared by treatment arm. | Baseline through study completion, an average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemodialysis, fluid overload, dialysis disequilibrium, intra-dialytic hypotension, dialysate sodium lowering