NCT03923933

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

Completed Phase 2 Results posted Last updated 23 November 2020

What this trial tests

Phase 2 trial testing Chlorthalidone in Renal Insufficiency, Chronic in 34 participants. Completed in 28 October 2019.

Timeline

18 June 2019

Primary endpoint
28 October 2019

28 October 2019

Quick facts

Lead sponsor	Hospital General de México Dr. Eduardo Liceaga
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	34
Start date	18 June 2019
Primary completion	28 October 2019
Estimated completion	28 October 2019
Sites	1 location across Mexico

Drugs / interventions tested

• Chlorthalidone — full drug profile →
• Bumetanide (BUMETANIDE) — full drug profile →

Conditions studied

• Renal Insufficiency, Chronic — all drugs for Renal Insufficiency, Chronic →

Sponsor

Hospital General de México Dr. Eduardo Liceaga

Who can join

18 and older, any sex, with Renal Insufficiency, Chronic. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Total Body Water Primary · Change from Basal to day 28

Measured by bioelectrical impedance analysis, compared to the initial measurement

Group	Value	95% CI
Placebo	-0.075	± 1.78
Treatment Grup	-4.36	± 3.29

Change in Mean Arterial Pressure Secondary · Change from Basal to day 28

decrease in blood pressure compared wit baseline measure (mmhg)

Group	Value	95% CI
Placebo	-5.4	± 14.3
Treatment Grup	-18.1	± 8.7

Change in the Fractional Excretion of Sodium Secondary · Change from Basal to day 28

Increase in the fractional excretion of sodium compared with the baseline measure

Group	Value	95% CI
Placebo	-0.348	± 3.48
Treatment Grup	0.598	± 2.29

Change in Extracellular Water Secondary · Change from Basal to day 28

Decrease in extracellular water measured by bioelectrical impedance analysis

Group	Value	95% CI
Placebo	-0.15	± 1.2
Treatment Grup	2.55	± 1.1

Change in Extracellular Water / Total Body Water Ratio Secondary · Change from Basal to day 28

Decrease in extracellular water / total body water ratio measured by bioelectrical impedance analysis

Group	Value	95% CI
Placebo	-0.24	± 1.42
Treatment Grup	-2.92	± 4.76

Change in Systolic Blood Pressure Secondary · Change from Basal to day 28

Group	Value	95% CI
Placebo	-10	± 23.3
Treatment Grup	-26.1	± 15.3

Change in Diastolic Blood Pressure Secondary · Change from Basal to day 28

Group	Value	95% CI
Placebo	-3.4	± 11.9
Treatment Grup	-13.5	± 10.7

Adverse events — posted to ClinicalTrials.gov

Time frame: 28 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/16 (0%)

Deaths: 0/16

Treatment Grup

Serious: 1/16 (6%)

Deaths: 0/16

Serious adverse events (1 terms)

Reaction	System	Placebo	Treatment Grup
Major adverse cardiovascular events	Cardiac disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	Placebo	Treatment Grup
Creatinine Increase	Renal and urinary disorders	—	—
hyperuricemia	Renal and urinary disorders	—	—
Hyponatremia	Renal and urinary disorders	—	—
hypokalemia	Renal and urinary disorders	—	—

Most-reported serious reactions: Major adverse cardiovascular events.

Data from ClinicalTrials.gov NCT03923933 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effect of the combination of bumetanide plus chlorthalidone on hypertension and volume overload in patients with chronic kidney disease stage 4-5 KDIGO without renal replacement therapy: a double-blind randomized HEBE-CKD trial.
   Solis-Jimenez F, Perez-Navarro LM, Cabrera-Barron R, Chida-Romero JA, et al · · 2022 · cited 4× · PMID 36127661 · DOI 10.1186/s12882-022-02930-4
2. Pathogenic Pathways and Therapeutic Strategies in Autosomal Dominant Polycystic Kidney Disease (ADPKD).
   Preval KM, Smith AO, Pazour GJ. · · 2025 · PMID 41608384 · DOI 10.33696/signaling.6.144
3. Effect of the combination of bumetanide plus chlorthalidone on hypertension and volume overload in patients with chronic kidney disease stage 4-5 KDIGO without renal replacement therapy: A double-blind randomized HEBE-CKD trial
   Solis-Jimenez F, Perez-Navarro LM, Cabrera-Barron R, Chida-Romero JA, et al · · 2022 · DOI 10.21203/rs.3.rs-1642925/v1