Cardiac Arrhythmia in Patients with End-Stage Renal Disease (CADDY)

The study will examine the presence of cardiac arrhythmias in patients receiving hemodialysis and the role of diabetes, hypoglycemia and parameters related to uremia and the dialysis procedure.

The study is designed as a prospective cohort study with 18 months follow-up. 70 patients receiving chronic hemodialysis will be recruited and equipped with implantable loop recorders (ILR): 35 patients with diabetes and 35 patients without diabetes.

Data collection during the follow-up includes continuous monitoring of the heart rhythm by the ILR for the entire follow-up period, continuous glucose monitoring for 10 days every second month, and monthly collection of blood samples and dialytic parameters.

After the initial 18-month follow-up, heart rhythm monitoring will continue until the ILR battery runs out for those participants who wish to continue.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus; Hypoglycemia; Cardiac Arrhythmia; End Stage Renal Disease on Dialysis
• Intervention / Treatment: Device: Loop recorder (Reveal LINQ, Medtronic); Device: Continuous Glucose Measurement (G6, Dexcom)

• Study Type: Observational
• Enrollment (Actual): 70

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Department of Nephrology, Rigshospitalet
  • Herlev, Denmark, 2730
    • Department of Nephrology, Herlev Hospital
  • Hillerød, Denmark
    • Department of Nephrology, North Zealand Hospital
  • Holbæk, Denmark, 4300
    • Department of Nephrology, Holbæk Sygehus

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

70 subjects receiving chronic hemodialysis therapy:

• 35 subjects with diabetes
• 35 subjects without diabetes

Description

Inclusion Criteria:

Patients with diabetes:

• Type 1 diabetes or Type 2 diabetes diagnosed according to the criteria of the World Health Organization
• Treated with glucose-lowering drugs at inclusion
• Receiving in-center maintenance hemodialysis for more than 3 months
• Age ≥ 18 years

Patients without diabetes:

• No known diagnosis of diabetes
• No previous treatment with glucose-lowering drugs
• HbA1c < 48 mmol/mol at screening
• Receiving in-center maintenance hemodialysis for more than 3 months
• Age ≥ 18 years

Exclusion Criteria:

For both groups:

• Cardiac pacemaker or implantable cardioverter defibrillator (ICD)
• Known permanent (chronic) atrial fibrillation
• History of sustained (> 30 seconds) ventricular tachycardia (more than 200 bpm) or ventricular fibrillation (note that ventricular premature beats is not considered an exclusion criterion)
• Known cardiac ion-channel disease (such as Long QT syndrome and Brugada syndrome)
• Not suitable for implantation (left-sided dialysis catheter or other condition expected to interfere with implantation)
• Previously complications in relation to wearing a CGM sensor, e.g. allergic reaction
• Inability to give written informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients receiving hemodialysis with diabetes; Patients receiving chronic hemodialysis with a diagnose of Type 1 diabetes or Type 2 diabetes (diagnosed according to the criteria of the World Health Organization) and receiving glucose-lowering treatment	Device: Loop recorder (Reveal LINQ, Medtronic); Implantation of a loop-recorder; Device: Continuous Glucose Measurement (G6, Dexcom); Monitoring with a continuous glucose monitor
Patients receiving hemodialysis without diabetes; Patients receiving chronic hemodialysis without diabetes (no known diagnosis of diabetes, and HbA1c < 48 mmol/mol at inclusion)	Device: Loop recorder (Reveal LINQ, Medtronic); Implantation of a loop-recorder; Device: Continuous Glucose Measurement (G6, Dexcom); Monitoring with a continuous glucose monitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically significant arrhythmias	Presence of one of the items in the combined endpoint of clinically significant arrhythmias defined as: Significant bradyarrhythmia (pause > 3 seconds or ≥ 4 beats at rate < 30 beats/min); Ventricular tachycardia (lasting ≥ 16 beats at rate ≥ 150 beats/min); Ventricular fibrillation	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sudden cardiac death	Sudden cardiac death	18 months
All-cause mortality	All-cause mortality	18 months
Cardiovascular death	Cardiovascular death	18 months
Atrial fibrillation	Presence of atrial fibrillation (lasting ≥ 2 minutes)	18 months
Supraventricular tachycardia other than atrial fibrillation	Presence of supraventricular tachycardia other than atrial fibrillation (lasting ≥ 16 beats at rate ≥ 150 beats/min)	18 months
Time to clinically significant arrhythmias, atrial fibrillation, or supraventricular tachycardia, respectively	Time to clinically significant arrhythmias, atrial fibrillation, or supraventricular tachycardia, respectively	18 months
Characterization of arrhythmias in terms of onset	Characterization of arrhythmias in terms of onset	18 months
Characterization of arrhythmias in terms of duration	Characterization of arrhythmias in terms of duration	18 months
Characterization of arrhythmias in terms of ventricular rate	Characterization of arrhythmias in terms of ventricular rate	18 months
Episodes of hypoglycemia	Episodes of hypoglycemia <3.9 mmol/L (defined as sensor glucose below 3.9 mmol/L for ≥ 15 min)	18 months
Time in range	Time in range (percentage of time and amount of time with sensor glucose in range 3.9-10.0 mmol/L)	18 months
Time below range (<3.9 mmol/L)	Time below range (percentage time and amount of time with sensor glucose <3.9 mmol/L)	18 months
Time below range (<3.0 mmol/L)	Time below range (percentage of time and amount of time with sensor glucose <3.0 mmol/L)	18 months
Time above range (>10.0 mmol/L)	Time above range (percentage of time and amount of time with sensor glucose >10.0 mmol/L)	18 months
Time above range (>13.9 mmol/L)	Time above range (percentage of time and amount of time with sensor glucose >13.9 mmol/L)	18 months
Mean sensor glucose	Mean sensor glucose derived from continuous glucose monitoring	18 months
Glycemic variability	Glycemic variability (defined as coefficient of variation and standard deviation) derived from continuous glucose monitoring	18 months
Arrhythmia leading to the implantation of a cardiac implantable electronic device	Presence of any arrhythmia leading to the implantation of a cardiac implantable electronic device	18 months
Arrhythmia leading to a medical intervention	Presence of any arrhythmia leading to a medical intervention (defined as any change in prescribed medication)	18 months
Adverse events	Presence of adverse events, including procedure related adverse events	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The temporal distribution of arrhythmias in relation to hypoglycemic events	Arrhythmic events one hour prior to hypoglycemia, during hypoglycemia and one hour post hypoglycemia	18 months
Difference in arrhythmias between patients with diabetes and patients without diabetes	Difference in arrhythmias between patients with diabetes and patients without diabetes	18 months
Arrhythmias during hypoglycemia compared to euglycemia/hyperglycemia	Arrhythmias during hypoglycemia compared to euglycemia and hyperglycemia	18 months
Difference in glycemic characteristics between patients with and without diabetes	Difference in glycemic characteristics between patients with and without diabetes	18 months
Correlation between pre-dialysis blood samples and arrhythmias	Correlation between pre-dialysis blood samples and arrhythmias	18 months
Correlation between dialysis parameters and arrhythmias	Correlation between dialysis parameters (dialysate electrolyte concentrations and temperature) and arrhythmias	18 months
Correlation between a decline in systolic blood pressure during dialysis and arrythmias	Correlation between a decline in systolic blood pressure ≥20 mmHg during a dialysis session and arrythmias	18 months
Correlation between ultrafiltration rate and arrhythmias	Correlation between ultrafiltration rate and arrhythmias	18 months
The temporal distribution of arrhythmias in relation to dialysis sessions	Arrhythmic events eight hours prior to dialysis, during dialysis, eight hours post dialysis, and in the interval between dialysis sessions	18 months
Correlation between baseline clinical variables and arrhythmias	Correlation between baseline clinical variables (baseline demographic and comorbidity characteristics) and arrhythmias	18 months
Correlation between baseline residual diuresis and arrhythmias	Correlation between baseline residual diuresis and arrhythmias	18 months
Correlation between baseline electrocardiographic and echocardiographic markers and arrhythmias	Correlation between baseline electrocardiographic (assessed by 12-lead ECG) and echocardiographic markers (assessed by transthoracic echo) and arrhythmias	18 months
Correlation between heart rate variability, daytime and nighttime heart rate, physical activity, and risk of arrhythmias	Correlation between heart rate variability, daytime and nighttime heart rate, physical activity, and risk of arrhythmias	18 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: University of Copenhagen; Herlev Hospital; Hillerod Hospital, Denmark; Steno Diabetes Center Copenhagen; Holbaek Sygehus

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): April 1, 2024
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (Actual): April 12, 2021

Study Record Updates

• Last Update Posted (Estimated): November 18, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Chronic Disease; Disease Attributes; Metabolic Diseases; Glucose Metabolism Disorders; Renal Insufficiency; Renal Insufficiency, Chronic; Hypoglycemia; Kidney Diseases; Kidney Failure, Chronic; Arrhythmias, Cardiac
• Other Study ID Numbers: H-20069767

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