Dialysate Sodium Lowering Trial (DeSaLT)

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Hemodialysis Complication; Fluid Overload; Dialysis Disequilibrium; Intra-dialytic Hypotension
• Intervention / Treatment: Other: Dialysate Sodium Lowering

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • DCI Boston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: InBody; Dialysis Clinic, Inc.
• Investigators: Principal Investigator: Dana Miskulin, MD, Tufts Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2017
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): April 2, 2019

Study Registration Dates

• First Submitted: April 27, 2017
• First Submitted That Met QC Criteria: May 4, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: May 31, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: hemodialysis; fluid overload; dialysis disequilibrium; intra-dialytic hypotension; dialysate sodium lowering
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Pharmaceutical Solutions; Dialysis Solutions
• Other Study ID Numbers: 12393

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No