Trial of Variable Dialysate Bicarbonate

Randomized, Controlled, Double-blind Trial of Lower Versus Higher Dialysate Bicarbonate in Hospitalized Maintenance Hemodialysis Patients

QTc prolongation and premature ventricular contractions (PVCs) are common in hemodialysis (HD) patients and are associated with sudden cardiac death.

It is known that higher dialysate bicarbonate is associated with more QTc prolongation during HD sessions.

This study aims to assess the effects of lower (30 mEq/L) versus higher (35 mEq/L) dialysate bicarbonate in adult maintenance HD patients admitted to the hospital.

The investigators will randomly assign subjects to lower versus higher dialysate bicarbonate concentrations during their hospital stay for up to a maximum of six HD sessions or until their hospital discharge.

Study Overview

• Status: Recruiting
• Conditions: Intradialytic Hypotension; Peri-dialytic Cardiac Rhythms; Electrolyte Changes; pH Changes; Adverse Symptoms
• Intervention / Treatment: Drug: Dialysate bicarbonate concentration; Device: Dialysate bicarbonate concentration - telemetry monitoring

• Study Type: Interventional
• Enrollment (Estimated): 141
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katherine S Ravi, MD, MPH; Phone Number: (617) 732-6383; Email: ksravi@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Katherine S Ravi, MD, MPH; Phone Number: 617-732-6383

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• prevalent end-stage renal disease, on maintenance HD > 90 days
• age ≥ 18 years old
• thrice weekly HD

Exclusion Criteria:

• hemoglobin < 8.0 g/dL
• pregnancy
• any physical, mental or medical condition which limited the ability to provide written informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lower dialysate bicarbonate; A lower dialysate bicarbonate will be used in the experimental arm (30 mEq/L).	Drug: Dialysate bicarbonate concentration; Assess how a lower dialysate bicarbonate affects: QTc duration during and between hemodialysis sessions; PVC burden during and between hemodialysis sessions; Clinically significant arrhythmia during and between hemodialysis sessions; Intradialytic hypotension; Adverse symptoms during hemodialysis sessions; Device: Dialysate bicarbonate concentration - telemetry monitoring; Patients will be monitored with telemetry on both arms of the trial.
Active Comparator: Higher dialysate bicarbonate; A higher dialysate bicarbonate will be used in the active comparator arm (35 mEq/L).	Drug: Dialysate bicarbonate concentration; Assess how a lower dialysate bicarbonate affects: QTc duration during and between hemodialysis sessions; PVC burden during and between hemodialysis sessions; Clinically significant arrhythmia during and between hemodialysis sessions; Intradialytic hypotension; Adverse symptoms during hemodialysis sessions; Device: Dialysate bicarbonate concentration - telemetry monitoring; Patients will be monitored with telemetry on both arms of the trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QTc prolongation	QTc prolongation, calculated as post-HD (just as HD finishing, generally 4 hours from start of HD session) minus pre-HD QTc duration, will be obtained via Holter monitoring.	During hemodialysis procedure (during dialysate administration)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PVC frequency	Holter monitors will be used to assess PVC frequency during HD sessions and in the subsequent inter-HD period. The investigators will also assess PVC coupling interval variability in these time intervals.	PVCs/hour will be recorded during HD sessions and for ~44-68 hours from the end of the hemodialysis session until the subsequent hemodialysis session.
Clinically significant arrhythmia	As described in the Monitoring in Dialysis (MiD) study, clinically significant arrhythmia is defined as: sustained ventricular tachycardia, bradycardia, asystole and symptomatic arrhythmias.	Clinically significant arrhythmia will be assessed during hemodialysis sessions and in the subsequent inter-hemodialysis period (until the subsequent hemodialysis session, up to 68 hours).
Intradialytic hypotension	Intradialytic hypotension will be defined as systolic blood pressure <90 during hemodialysis. The investigators will also conduct sensitivity analyses using alternative definitions of intradialytic hypotension (e.g. nadir intra-hemodialysis systolic blood pressure <90mmHg if pre-hemodialysis systolic blood pressure is <160mmHg or nadir intra-hemodialysis systolic blood pressure <100mmHg if pre-hemodialysis systolic blood pressure is ≥160mmHg). Additionally, the investigators will examine the overall mean decline in systolic blood pressure during hemodialysis as a continuous outcome (intra-hemodialysis systolic blood pressure decline=pre-hemodialysis systolic blood pressure minus nadir systolic blood pressure during hemodialysis).	Blood pressures will be measured every 15 minutes during HD sessions.
Electrolytes	Samples are collected from the hemodialysis circuit (no extra blood sticks) for freezing for comprehensive metabolic panels.	Obtained pre- and post-hemodialysis study sessions (just as hemodialysis finishing, generally 4 hours from start of hemodialysis session).
pH	Samples are collected from the hemodialysis circuit (no extra blood sticks) for immediate blood gas analysis.	Obtained pre- and post-hemodialysis study sessions (just as hemodialysis finishing, generally 4 hours from start of hemodialysis session).
Ionized calcium level	Samples are collected from the hemodialysis circuit (no extra blood sticks) for immediate evaluation of ionized calcium level.	Obtained pre- and post-hemodialysis study sessions (just as hemodialysis finishing, generally 4 hours from start of hemodialysis session).
Adverse symptoms	The investigators will administer the modified Edmonton Symptom Assessment System (mESAS). The mESAS measures patient-reported severity of pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath and pruritus using a 0-10 score (anchored by "No" at 0 and "Severe" at 10). A validated Spanish version is available and a translator will help to administer the questionnaire as well as with all communication with patients in any language other than English.	Questionnaires will be administered during the last 10 minutes of hemodialysis sessions.

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Katherine S Ravi, MD, MPH, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: April 3, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Pharmaceutical Solutions; Dialysis Solutions
• Other Study ID Numbers: 2022P002944

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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