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

NCT03923933 | Completed Phase 2 Results DMC

• 1 other identifier: DI/19/105-B/03/018
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Insufficiency, Chronic

Keywords

Diuretics; Bumetanide; Chlorthalidone; Chronic Kidney Disease; Volume Overload

Outcome Measures

Primary Outcomes (1)

• Change in Total Body Water

  Measured by bioelectrical impedance analysis, compared to the initial measurement

  Change from Basal to day 28

Secondary Outcomes (6)

• Change in Mean Arterial Pressure

  Change from Basal to day 28

• Change in the Fractional Excretion of Sodium

  Change from Basal to day 28

• Change in Extracellular Water

  Change from Basal to day 28

• Change in Extracellular Water / Total Body Water Ratio

  Change from Basal to day 28

• Change in Systolic Blood Pressure

  Change from Basal to day 28

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Treatment grup

EXPERIMENTAL

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; Drug: Bumetanide

Interventions

Chlorthalidone DRUG

Chlorthalidone

Treatment grup

Bumetanide DRUG

Bumetanide

Placebo; Treatment grup

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital General de México Dr. Eduardo Liceaga: lead

Study Sites (1)

Hospital General de Mexico

Mexico City, 06720, Mexico

Location

Related Publications (50)

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MeSH Terms

Conditions

Renal Insufficiency, Chronic; Edema

Interventions

Chlorthalidone; Bumetanide

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids

Results Point of Contact

• Title: Rafael Vadez-Ortiz M.D. PhD
• Organization: Head of Nephrology Hospital General de México

rafavaldez@gmail.com

+52 2789-2000

Study Officials

• Fabio Solis-Jimenez, M.D.

  Hospital General de México Dr. Eduardo Liceaga

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: April 23, 2019
• Study Start: June 18, 2019
• Primary Completion: October 28, 2019
• Study Completion: October 28, 2019
• Last Updated: November 23, 2020
• Results First Posted: March 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)