Trial Outcomes & Findings for Chlortalidone and Bumetanide in Advanced Chronic Kidney Disease: HEBE-CKD Trial (NCT NCT03923933)
NCT ID: NCT03923933
Last Updated: 2020-11-23
Results Overview
Measured by bioelectrical impedance analysis, compared to the initial measurement
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
Change from Basal to day 28
Results posted on
2020-11-23
Participant Flow
Patients were recruited from the nephrology clinic in the Hospital General de México, between May and August 2019. All those with stage 4-5 chronic kidney disease, who had chronic use of loop diuretics and hypertension, were invited to perform an impedance measurement. Those with volume overload were invited to participate in the protocol.
Participant milestones
| Measure |
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.
Bumetanide: Bumetanide
|
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
17
|
|
Overall Study
COMPLETED
|
16
|
16
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
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.
Bumetanide: Bumetanide
|
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.6 years
STANDARD_DEVIATION 8.1 • n=16 Participants
|
54.8 years
STANDARD_DEVIATION 10 • n=16 Participants
|
57.2 years
STANDARD_DEVIATION 9.34 • n=32 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=16 Participants
|
10 Participants
n=16 Participants
|
22 Participants
n=32 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=16 Participants
|
6 Participants
n=16 Participants
|
10 Participants
n=32 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Mexico
|
16 participants
n=16 Participants
|
16 participants
n=16 Participants
|
32 participants
n=32 Participants
|
|
Total body water
|
33.1 liters
n=16 Participants
|
32.7 liters
n=16 Participants
|
33.1 liters
n=32 Participants
|
|
Extracellular water
|
16.2 liters
n=16 Participants
|
16.4 liters
n=16 Participants
|
16.3 liters
n=32 Participants
|
|
Extracellular water/Total Body Water
|
50.9 percentage
STANDARD_DEVIATION 3.5 • n=16 Participants
|
50 percentage
STANDARD_DEVIATION 3.6 • n=16 Participants
|
50.4 percentage
STANDARD_DEVIATION 3.5 • n=32 Participants
|
|
systolic blood pressure
|
146.8 mmHg
STANDARD_DEVIATION 18.2 • n=16 Participants
|
142 mmHg
STANDARD_DEVIATION 22.6 • n=16 Participants
|
144.6 mmHg
STANDARD_DEVIATION 20.3 • n=32 Participants
|
|
diastolic blood pressure
|
77.8 mmHg
STANDARD_DEVIATION 11.3 • n=16 Participants
|
81.8 mmHg
STANDARD_DEVIATION 10.9 • n=16 Participants
|
79.7 mmHg
STANDARD_DEVIATION 11.1 • n=32 Participants
|
|
Mean arterial pressure
|
100.6 mmHg
STANDARD_DEVIATION 12.8 • n=16 Participants
|
102.1 mmHg
STANDARD_DEVIATION 10.9 • n=16 Participants
|
101 mmHg
STANDARD_DEVIATION 12.7 • n=32 Participants
|
|
serum creatinine
|
3.5 mg/dL
n=16 Participants
|
3.6 mg/dL
n=16 Participants
|
3.6 mg/dL
n=32 Participants
|
|
serum urea
|
124 mg/dL
n=16 Participants
|
125 mg/dL
n=16 Participants
|
125 mg/dL
n=32 Participants
|
|
glomerular filtration rate
|
15.69 ml/min/1.73m2
STANDARD_DEVIATION 7.64 • n=16 Participants
|
16.52 ml/min/1.73m2
STANDARD_DEVIATION 8.76 • n=16 Participants
|
16.1 ml/min/1.73m2
STANDARD_DEVIATION 8.14 • n=32 Participants
|
|
Cause of chronic kidney disease
Diabetes
|
11 Participants
n=16 Participants
|
11 Participants
n=16 Participants
|
22 Participants
n=32 Participants
|
|
Cause of chronic kidney disease
Hypertension
|
1 Participants
n=16 Participants
|
1 Participants
n=16 Participants
|
2 Participants
n=32 Participants
|
|
Cause of chronic kidney disease
Lupus
|
1 Participants
n=16 Participants
|
0 Participants
n=16 Participants
|
1 Participants
n=32 Participants
|
|
Cause of chronic kidney disease
Unknown
|
3 Participants
n=16 Participants
|
4 Participants
n=16 Participants
|
7 Participants
n=32 Participants
|
|
Seric sodium
|
138.3 meq/l
STANDARD_DEVIATION 4.3 • n=16 Participants
|
137.4 meq/l
STANDARD_DEVIATION 4.9 • n=16 Participants
|
137.9 meq/l
STANDARD_DEVIATION 4.6 • n=32 Participants
|
|
serum potassium
|
5.1 meq/l
STANDARD_DEVIATION 0.74 • n=16 Participants
|
5.3 meq/l
STANDARD_DEVIATION 0.64 • n=16 Participants
|
5.2 meq/l
STANDARD_DEVIATION 0.68 • n=32 Participants
|
|
Urinary sodium
|
64.7 meq/l
STANDARD_DEVIATION 23.4 • n=16 Participants
|
62.7 meq/l
STANDARD_DEVIATION 20.6 • n=16 Participants
|
63.7 meq/l
STANDARD_DEVIATION 21.6 • n=32 Participants
|
|
Urinary chlorine
|
60.2 meq/l
STANDARD_DEVIATION 27.4 • n=16 Participants
|
62.3 meq/l
STANDARD_DEVIATION 18.6 • n=16 Participants
|
61.2 meq/l
STANDARD_DEVIATION 23.1 • n=32 Participants
|
PRIMARY outcome
Timeframe: Change from Basal to day 28Measured by bioelectrical impedance analysis, compared to the initial measurement
Outcome measures
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Change in Total Body Water
|
-0.075 litres
Standard Deviation 1.78
|
-4.36 litres
Standard Deviation 3.29
|
SECONDARY outcome
Timeframe: Change from Basal to day 28decrease in blood pressure compared wit baseline measure (mmhg)
Outcome measures
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Change in Mean Arterial Pressure
|
-5.4 mmHg
Standard Deviation 14.3
|
-18.1 mmHg
Standard Deviation 8.7
|
SECONDARY outcome
Timeframe: Change from Basal to day 28Increase in the fractional excretion of sodium compared with the baseline measure
Outcome measures
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Change in the Fractional Excretion of Sodium
|
-0.348 percentage of sodium excreted
Standard Deviation 3.48
|
0.598 percentage of sodium excreted
Standard Deviation 2.29
|
SECONDARY outcome
Timeframe: Change from Basal to day 28Decrease in extracellular water measured by bioelectrical impedance analysis
Outcome measures
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Change in Extracellular Water
|
-0.15 litres
Standard Deviation 1.2
|
2.55 litres
Standard Deviation 1.1
|
SECONDARY outcome
Timeframe: Change from Basal to day 28Decrease in extracellular water / total body water ratio measured by bioelectrical impedance analysis
Outcome measures
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Change in Extracellular Water / Total Body Water Ratio
|
-0.24 percentage of ECW/TBW
Standard Deviation 1.42
|
-2.92 percentage of ECW/TBW
Standard Deviation 4.76
|
SECONDARY outcome
Timeframe: Change from Basal to day 28Outcome measures
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Change in Systolic Blood Pressure
|
-10 mmHg
Standard Deviation 23.3
|
-26.1 mmHg
Standard Deviation 15.3
|
SECONDARY outcome
Timeframe: Change from Basal to day 28Outcome measures
| Measure |
Placebo
n=16 Participants
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 Participants
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Change in Diastolic Blood Pressure
|
-3.4 mmHg
Standard Deviation 11.9
|
-13.5 mmHg
Standard Deviation 10.7
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment Grup
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=16 participants at risk
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 participants at risk
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Cardiac disorders
Major adverse cardiovascular events
|
0.00%
0/16 • 28 days
|
6.2%
1/16 • Number of events 1 • 28 days
|
Other adverse events
| Measure |
Placebo
n=16 participants at risk
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.
Bumetanide: Bumetanide
|
Treatment Grup
n=16 participants at risk
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.
Chlorthalidone: Chlorthalidone
Bumetanide: Bumetanide
|
|---|---|---|
|
Renal and urinary disorders
Creatinine Increase
|
25.0%
4/16 • Number of events 4 • 28 days
|
68.8%
11/16 • Number of events 11 • 28 days
|
|
Renal and urinary disorders
Hyponatremia
|
6.2%
1/16 • Number of events 1 • 28 days
|
12.5%
2/16 • Number of events 2 • 28 days
|
|
Renal and urinary disorders
hypokalemia
|
0.00%
0/16 • 28 days
|
12.5%
2/16 • Number of events 2 • 28 days
|
|
Renal and urinary disorders
hyperuricemia
|
25.0%
4/16 • Number of events 4 • 28 days
|
25.0%
4/16 • Number of events 4 • 28 days
|
Additional Information
Rafael Vadez-Ortiz M.D. PhD
Head of Nephrology Hospital General de México
Phone: +52 2789-2000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place