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

Study Overview
=================
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.

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

Conditions
-----------------
Renal Insufficiency, Chronic

Intervention / Treatment
-----------------
* Drug: Chlorthalidone
* Drug: Bumetanide


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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. | Drug: Bumetanide<br>* Bumetanide<br>|
| Experimental: Treatment grup<br>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. | Drug: Chlorthalidone<br>* Chlorthalidone<br>Drug: Bumetanide<br>* Bumetanide<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Body Water | Measured by bioelectrical impedance analysis, compared to the initial measurement | Change from Basal to day 28 | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diuretics, Bumetanide, Chlorthalidone, Chronic Kidney Disease, Volume Overload