Volume,Sodium and Blood Pressure Management in HD

Study Overview
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Brief Summary
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The purpose of this study to conduct a pilot, randomized trial in stable HD patients to evaluate the effect of gradual, step-wise reduction of post-hemodialysis target weight, combined with diligent dietary sodium restriction and reduction in dialysate sodium exposure on hydration/volume status and blood pressure (BP) control.

Detailed Description
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Fluid-weight management is critical for dialysis patients 1, 2. Previous clinical trials have not comprehensively addressed the application of a strategy combining both sodium restriction and a progressive, but gradual challenge of post dialysis target weight for BP and fluid-weight management in hemodialysis (HD). The investigators postulate that a protocolized, stepwise and gradual challenge of post-hemodialysis target weight when combined with diligent dietary sodium restriction <2000mg sodium/day, will lead to better hydration/volume status and BP control in HD patients. A randomized, two parallel arm trial (n=40) among HD patients is proposed, that compares this comprehensive strategy in one group versus 'usual' HD volume/hydration and BP management in the control group. The two primary outcomes are change in volume/hydration status (assessed by bioelectrical impedance analysis-BIA) and change in BP (pre-dialysis in-center readings, home self-monitored readings as well as 44-hour interdialytic BP). Secondary outcomes include change in target post-dialysis weight, slope of on-line relative plasma volume monitoring (using Crit-line monitors), utilization and change, if any, in antihypertensive regimen, change in interdialytic weight gain, objectively assessed salt-appetite, thirst score, frequency of intradialytic hypotension, cramps and duration of post-dialysis fatigue and recovery, time to achievement of dry weight and laboratory parameters (hemoglobin, albumin, brain natriuretic peptide-BNP, aldosterone and hsCRP). The trial will be 14-weeks in duration and will involve comprehensive assessment of study parameters at baseline, middle and end of the trial. It is anticipated that the trial will lead to the the development of a simple and practical approach for volume and BP control in HD patients that will subsequently need to be studied on a larger scale, i.e., a larger, multicenter study with hard endpoints of death and hospitalization.

Official Title
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Fluid-Weight, Volume, Sodium, Blood Pressure Management in Hemodialysis by Limiting Intradialytic and Inter-dialytic Exposure to Sodium and Protocol-based Challenge of Post-dialysis Target Weight: A Pilot and Feasibility Trial

Conditions
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End Stage Renal Failure

Intervention / Treatment
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* Behavioral: Lower sodium intervention
* Other: Progressive Challenge to Post Dialysis Weight


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable adult HD patient (age 18-85 years) Usual in-center pre-dialysis systolic blood pressure of ≥130mmHg. For this purpose mean of pre-dialysis sitting blood pressures for the past one month prior to randomization will be applied for evaluation of inclusion criteria. Able and willing to adhere to study protocol Exclusion Criteria: Recent acute illness (≤1month) Recent hospitalization (≤1month) Any psychological condition that could interfere with compliance with study protocol. Amputation of both lower limbs (due to interference with electric current for BIA measurement) Pacemaker, defibrillator, implantable pump, artificial joint, pins, plates or other types of metal objects in the body (other than dental fillings), if their presence interfere with appropriate measurements. In such patients consideration will be given to only doing the calf-BIA measurements and not the total body, at the discretion of the investigators. Use of any investigational product or device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments. Pregnancy or lactation (pregnancy test will be applied only if the patient is in the reproductive age range). Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Lower sodium intervention: Dietary sodium restriction of ≤2.0 g/day or ≤85 mmol/day Lower dialysate sodium at 137 mmol/L. Progressive Challenge to Post Dialysis Weight: The existing target post-HD weight will be progressively challenged by removing additional fluid in small increments. | Behavioral: Lower sodium intervention<br>* 1. Lower sodium intervention: Dietary sodium restriction of ≤2.0 g/day or ≤85 mmol/day (approximately >180-200mmol/day in the average American diet). Sodium restriction will be implemented using intensive dietary counseling performed weekly by a registered study dietitian using the motivational interviewing technique. Lower dialysate sodium at 137 mmol/L, if perchance a different concentration of dialysate is used for the enrolled individual, although this is unlikely in both the UM associated units, where for some time now, dialysate concentration of 137 mmol/L is currently being used as standard practice. Investigators will ensure that this sodium concentration is indeed used for all study participants.<br>Other: Progressive Challenge to Post Dialysis Weight<br>* The existing target post-HD weight will be progressively challenged by removing additional fluid in small increments, unless clinical evidence of volume depletion or hypotension precludes this challenge in the intervention arm. To avoid the occurrence of intradialytic hypotension, the ultrafiltration rate shall not exceed15 ml/kg/hour and post dialysis weight will not be reduced by more than 0.5 kg per dialysis session. In some patients, this may warrant prolongation of the treatment time to achieve lowering of target post dialysis weight, and this process of target weight reduction may need to continue up to and through the interim assessment phase (6-8 weeks).<br>|
| No Intervention: Control<br>Usual care in addition to Blood pressure monitoring and and Hydration status monitoring | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure | Change in blood pressure (pre-dialysis in-center blood pressure readings, ABPM and home BP monitoring) | Pre-dialysis BP measure at Baseline, 6 Weeks and 12 weeks. ABPM measured at baseline and 12 Weeks. Home BP measure through out the 12week period on non-dialysis days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-dialysis Weight | Change in target post-dialysis weight | 12weeks | 
| Heart Rate | Change in heart rate | 12 weeks | 
| Plasma Volume | Slope of relative plasma volume monitoring | 12 Weeks | 
| Medication Use | Change in the utilization of antihypertensive medication ( number of medication and dose) | 12 Weeks | 
| Interdialytic Weight gain | Change in the mid-week interdialytic weight gain | 12 Weeks | 
| Intradialytic Hypotension | Frequency of intradialytic hypotension; defined as drop in systolic blood pressure associated with symptoms suggestive of low blood pressure such as lightheadedness, dizziness, sweating, etc., or decrease in intradialytic systolic blood pressure to less than 90 mmHg. | 12 Weeks | 
| Salt Appetite | A measure of salt taste impairment and preference | Baseline, 6 week and 12 week | 
| Thirst Score | A measure of general thirst. | Baseline, 6 week, 12 weeks | 
| Post-dialysis fatigue | A measure of post-dialysis fatigue and recovery after each treatment session | Baseline, 6 Weeks & 12 Weeks | 
| Routine Labs | o Routine labs including CBC, renal panel, hsCRP and brain natriuretic peptide (BNP). Interdialytic urine collection for residual renal function (urea and creatinine clearance) estimation will be made. Blood and urine samples will be archived for later analysis for biomarkers such as asymmetric dimethyl arginine (ADMA), plasma aldosterone, and urinary neutrophil gelatinase-associated lipocalin (NGAL), respectively | Baseline and 12Week | 
| True Dry Weight | Time to achievement of true 'dry weight' (in the intervention arm only) | 12 weeks | 
| Hydration Status | Change in hydration status, as measured by BIA, using whole body and segmental techniques. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Blood Pressure, Hydration Status, Low-sodium diet