Chlortalidone and Bumetanide in Advanced Chronic Kidney Disease: HEBE-CKD Trial

Phase 2

Completed

• Conditions: Renal Insufficiency, Chronic
• Interventions: Drug: Chlorthalidone; Drug: Bumetanide

• Registration Number: NCT03923933
• Lead Sponsor: Hospital General de México Dr. Eduardo Liceaga

Brief Summary

This study aims to demonstrate the possible benefit of a treatment based on double diuretic in patients with chronic kidney disease and severely impaired glomerular filtration rate. This is based on previous observations where the investigators found that volume overload is a frequent condition within this population and is strongly linked to an increase in morbidity and mortality. The investigators consider that this therapy could be beneficial given that most of these patients are treated with loop diuretics, however, with the passage of time, adaptive changes in the distal nephron occur that promote a decrease in the treatment effect. In this sense, thiazide diuretics at appropriate doses could 'break' the resistance, since their mechanism of action antagonizes the resistance mechanism. Unfortunately, to this day, this treatment has not been fully evaluated. Particularly in this type of population.

The investigators developed a study proposed as a double blind randomized clinical trial, where the population will be divided into two groups. A group will be given the standard treatment based on loop diuretic (bumetanide), while the other group will receive the intervention (bumetanide plus chlorthalidone). After a 30-day follow-up period, the results will be measured.

With respect to the effectiveness of the treatment, the decrease in volume overload by bioimpedance will be measured. While the occurrence of adverse effects during the same monitoring period will be observed.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-18
• Study First Submitted QC: 2019-04-22
• Study First Posted: 2019-04-23
• Study Start: 2019-06-18
• Primary Completion: 2019-10-28
• Study Completion: 2019-10-28
• Results First Submitted: 2020-02-05
• Results First Submitted QC: 2020-03-02
• Results First Posted: 2020-03-10
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-04
• Last Update Posted: 2020-11-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• glomerular filtration rate less than 30 ml / min / 1.73m
• Without replacement therapy (dialysis or hemodialysis)
• Volume overload
• At least 100 ml per day of residual diuresis
• Use of a loop diuretic for at least one month

Exclusion Criteria

• Allergies known to diuretics
• Patients with severe infections
• Patients with hemodynamic instability
• Amputees
• Patients with cognitive impairment
• Patients with acute renal failure
• Patients with graft loss

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment grup	Chlorthalidone	This group will receive 3 milligrams of bumetanide plus 50 milligrams of chlorthalidone per day, for a week. If the dose is well tolerated, it will be increased to 4 milligrams of bumetanide and 100 milligrams of chlorthalidone per day.
Treatment grup	Bumetanide	This group will receive 3 milligrams of bumetanide plus 50 milligrams of chlorthalidone per day, for a week. If the dose is well tolerated, it will be increased to 4 milligrams of bumetanide and 100 milligrams of chlorthalidone per day.
Placebo	Bumetanide	This group will receive 3 milligrams of bumetanide per day for a week plus placebo (starch) that will simulate the chlorthalidone dose of the treatment group. In case the dose is well tolerated, the dose of bumetanide will be increased to 4 milligrams per day.

Primary Outcome Measures

Name	Time	Method
Change in Total Body Water	Change from Basal to day 28	Measured by bioelectrical impedance analysis, compared to the initial measurement

Secondary Outcome Measures

Name	Time	Method
Change in the Fractional Excretion of Sodium	Change from Basal to day 28	Increase in the fractional excretion of sodium compared with the baseline measure
Change in Extracellular Water	Change from Basal to day 28	Decrease in extracellular water measured by bioelectrical impedance analysis
Change in Extracellular Water / Total Body Water Ratio	Change from Basal to day 28	Decrease in extracellular water / total body water ratio measured by bioelectrical impedance analysis
Change in Systolic Blood Pressure	Change from Basal to day 28
Change in Mean Arterial Pressure	Change from Basal to day 28	decrease in blood pressure compared wit baseline measure (mmhg)
Change in Diastolic Blood Pressure	Change from Basal to day 28

Trial Locations

Locations (1)

Hospital General de Mexico; 🇲🇽 Mexico City, Mexico