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

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: October 28, 2019

Interventions

  • Drug: Chlorthalidone
    • Chlorthalidone
  • Drug: Bumetanide
    • Bumetanide

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo
    • 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.
  • Experimental: Treatment grup
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Change in Total Body Water
    • Time Frame: Change from Basal to day 28
    • Measured by bioelectrical impedance analysis, compared to the initial measurement
  • Change in Mean Arterial Pressure
    • Time Frame: Change from Basal to day 28
    • decrease in blood pressure compared wit baseline measure (mmhg)

Secondary Measures

  • Change in the Fractional Excretion of Sodium
    • Time Frame: Change from Basal to day 28
    • Increase in the fractional excretion of sodium compared with the baseline measure
  • Change in Extracellular Water
    • Time Frame: Change from Basal to day 28
    • Decrease in extracellular water measured by bioelectrical impedance analysis
  • Change in Extracellular Water / Total Body Water Ratio
    • Time Frame: Change from Basal to day 28
    • Decrease in extracellular water / total body water ratio measured by bioelectrical impedance analysis
  • Change in Systolic Blood Pressure
    • Time Frame: Change from Basal to day 28
  • Change in Diastolic Blood Pressure
    • Time Frame: Change from Basal to day 28

Participating in This Clinical Trial

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
  • Gender Eligibility: All

    Minimum Age: 18 Years

    Maximum Age: N/A

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Hospital General de México Dr. Eduardo Liceaga
    • Provider of Information About this Clinical Study
      • Principal Investigator: Fabio Solis-Jimenez, Principal Investigator – Hospital General de México Dr. Eduardo Liceaga
    • Overall Official(s)
      • Fabio Solis-Jimenez, M.D., Principal Investigator, Hospital General de México Dr. Eduardo Liceaga

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