Trial Outcomes & Findings for Chlorthalidone in Chronic Kidney Disease (NCT NCT02841280)

NCT ID: NCT02841280

Last Updated: 2023-05-15

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 160 participants
• Primary outcome timeframe: Baseline to 12 weeks
• Results posted on: 2023-05-15

Participant Flow

Patients were recruited by screening for potential participants for eligibility at 3 medical centers between June 29, 2016 and January 7, 2021. The first participant consented on July 14, 2016, and the last participant was randomized on January 20, 2021.

Of the 403 consented patients, 160 met inclusion criteria and were randomized to treatment. Thus, 160 are considered enrolled for the purposes of this report.

Participant milestones

Measure	Chlorthalidone Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Overall Study STARTED	81	79
Overall Study COMPLETED	67	73
Overall Study NOT COMPLETED	14	6

Reasons for withdrawal

Measure	Chlorthalidone Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Overall Study Adverse Event	2	1
Overall Study Death	1	0
Overall Study Lost to Follow-up	2	2
Overall Study Withdrawal by Subject	7	3
Overall Study Stop Point: BP above threshold	2	0

Baseline Characteristics

Chlorthalidone in Chronic Kidney Disease

Baseline characteristics by cohort

Measure	Chlorthalidone n=81 Participants Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 Participants Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Total n=160 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants	33 Participants n=7 Participants	67 Participants n=5 Participants
Age, Categorical >=65 years	47 Participants n=5 Participants	46 Participants n=7 Participants	93 Participants n=5 Participants
Age, Continuous	66.2 years STANDARD_DEVIATION 10.8 • n=5 Participants	66.7 years STANDARD_DEVIATION 10.8 • n=7 Participants	66.4 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	62 Participants n=7 Participants	124 Participants n=5 Participants
Race/Ethnicity, Customized Race or Ethnic Group · White	46 Participants n=5 Participants	47 Participants n=7 Participants	93 Participants n=5 Participants
Race/Ethnicity, Customized Race or Ethnic Group · Black	32 Participants n=5 Participants	32 Participants n=7 Participants	64 Participants n=5 Participants
Race/Ethnicity, Customized Race or Ethnic Group · Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race or Ethnic Group · Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	81 participants n=5 Participants	79 participants n=7 Participants	160 participants n=5 Participants
Medical History of Diabetes Mellitus	60 Participants n=5 Participants	61 Participants n=7 Participants	121 Participants n=5 Participants
Cause of Chronic Kidney Disease Diabetes	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants
Cause of Chronic Kidney Disease Hypertension	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Cause of Chronic Kidney Disease Glomerulonephritis	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Cause of Chronic Kidney Disease Obstructive Uropathy	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Cause of Chronic Kidney Disease Polycystic Kidney Disease	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Cause of Chronic Kidney Disease Other	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Current Smoking	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Height	171.7 cm STANDARD_DEVIATION 11.3 • n=5 Participants	173.0 cm STANDARD_DEVIATION 8.6 • n=7 Participants	172.3 cm STANDARD_DEVIATION 10.1 • n=5 Participants
Weight	97.4 kg STANDARD_DEVIATION 23.6 • n=5 Participants	95.8 kg STANDARD_DEVIATION 23.5 • n=7 Participants	96.6 kg STANDARD_DEVIATION 23.6 • n=5 Participants
Body-Mass Index	33.0 kg/m^2 STANDARD_DEVIATION 7.0 • n=5 Participants	32.0 kg/m^2 STANDARD_DEVIATION 7.4 • n=7 Participants	32.5 kg/m^2 STANDARD_DEVIATION 7.2 • n=5 Participants
Hip Circumference	115.9 cm STANDARD_DEVIATION 14.9 • n=5 Participants	114.6 cm STANDARD_DEVIATION 15.0 • n=7 Participants	115.3 cm STANDARD_DEVIATION 14.9 • n=5 Participants
Waist Circumference	115.3 cm STANDARD_DEVIATION 17.0 • n=5 Participants	115.4 cm STANDARD_DEVIATION 16.6 • n=7 Participants	115.3 cm STANDARD_DEVIATION 16.8 • n=5 Participants
Waist-to-Hip Ratio	1.011 ratio STANDARD_DEVIATION 0.078 • n=5 Participants	0.998 ratio STANDARD_DEVIATION 0.074 • n=7 Participants	1.005 ratio STANDARD_DEVIATION 0.076 • n=5 Participants
Systolic Blood Pressure	141.2 mm Hg STANDARD_DEVIATION 15.1 • n=5 Participants	138.7 mm Hg STANDARD_DEVIATION 16.0 • n=7 Participants	140.0 mm Hg STANDARD_DEVIATION 15.6 • n=5 Participants
Diastolic Blood Pressure	69.2 mm Hg STANDARD_DEVIATION 12.3 • n=5 Participants	67.9 mm Hg STANDARD_DEVIATION 13.9 • n=7 Participants	68.6 mm Hg STANDARD_DEVIATION 13.1 • n=5 Participants
Pulse Rate	66.5 beats/min STANDARD_DEVIATION 11.7 • n=5 Participants	64.3 beats/min STANDARD_DEVIATION 11.1 • n=7 Participants	65.4 beats/min STANDARD_DEVIATION 11.4 • n=5 Participants
Estimated Glomerular Filtration Rate	23.5 ml/min/1.73 m^2 STANDARD_DEVIATION 4.2 • n=5 Participants	22.8 ml/min/1.73 m^2 STANDARD_DEVIATION 4.2 • n=7 Participants	23.2 ml/min/1.73 m^2 STANDARD_DEVIATION 4.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Outcome measures

Measure	Chlorthalidone n=81 Participants Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 Participants Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo.	-11.0 mm Hg Interval -13.9 to -8.1	-0.5 mm Hg Interval -3.5 to 2.5

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Outcome measures

Measure	Chlorthalidone n=81 Participants Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 Participants Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo Percent change in albuminuria 4 weeks from baseline in UACR	-41 percentage of change in UACR Interval -49.0 to -30.0	-7 percentage of change in UACR Interval -20.0 to 9.0
Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo Percent change in albuminuria 8 weeks from baseline in UACR	-45 percentage of change in UACR Interval -53.0 to -35.0	-3 percentage of change in UACR Interval -17.0 to 13.0
Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo Percent change in albuminuria 12 weeks from baseline in UACR	-52 percentage of change in UACR Interval -59.0 to -43.0	-4 percentage of change in UACR Interval -18.0 to 12.0

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Outcome measures

Measure	Chlorthalidone n=81 Participants Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 Participants Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change 4 weeks from baseline in aldosterone	57 percentage of change Interval 34.0 to 84.0	16 percentage of change Interval -1.0 to 36.0
Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change 8 weeks from baseline in aldosterone	65 percentage of change Interval 40.0 to 95.0	12 percentage of change Interval -4.0 to 32.0
Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change 12 weeks from baseline in aldosterone	52 percentage of change Interval 28.0 to 79.0	8 percentage of change Interval -8.0 to 27.0
Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change 4 weeks from baseline in renin	57 percentage of change Interval 45.0 to 70.0	14 percentage of change Interval 5.0 to 23.0
Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change 8 weeks from baseline in renin	67 percentage of change Interval 54.0 to 81.0	5 percentage of change Interval -3.0 to 14.0
Change From Baseline at Each 4 Week Visit in Log of Aldosterone and Log of Renin in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change 12 weeks from baseline in renin	64 percentage of change Interval 50.0 to 78.0	15 percentage of change Interval 6.0 to 25.0

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Outcome measures

Measure	Chlorthalidone n=81 Participants Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 Participants Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Change From Baseline at Each 4 Week Visit in Log of N-terminal Pro B-type Natriuretic Peptide (NTproBNP) in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change from 4 weeks from baseline in NTproBNP	-25 percentage of change in NTproBNP Interval -36.0 to -14.0	-14 percentage of change in NTproBNP Interval -26.0 to 0.0
Change From Baseline at Each 4 Week Visit in Log of N-terminal Pro B-type Natriuretic Peptide (NTproBNP) in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change from 8 weeks from baseline in NTproBNP	-32 percentage of change in NTproBNP Interval -42.0 to -21.0	5 percentage of change in NTproBNP Interval -9.0 to 22.0
Change From Baseline at Each 4 Week Visit in Log of N-terminal Pro B-type Natriuretic Peptide (NTproBNP) in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Percent change from 12 weeks from baseline in NTproBNP	-30 percentage of change in NTproBNP Interval -39.0 to -19.0	-11 percentage of change in NTproBNP Interval -23.0 to 2.0

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Outcome measures

Measure	Chlorthalidone n=81 Participants Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 Participants Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Change From Baseline at Each 4 Week Visit in Body Volume in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Change in body volume 4 weeks from baseline	-1.1 Liters Interval -1.7 to -0.6	0.2 Liters Interval -0.3 to 0.7
Change From Baseline at Each 4 Week Visit in Body Volume in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Change in body volume 8 weeks from baseline	-1.7 Liters Interval -2.2 to -1.1	0.3 Liters Interval -0.2 to 0.8
Change From Baseline at Each 4 Week Visit in Body Volume in the Chlorthalidone Group Compared to Placebo. No Adjustments Will be Made for Multiple Comparisons. Change in body volume 12 weeks from baseline	-2 Liters Interval -2.6 to -1.5	0.3 Liters Interval -0.3 to 0.8

Adverse Events

Chlorthalidone

Serious events: 8 serious events

Other events: 74 other events

Deaths: 1 deaths

Placebo

Serious events: 11 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Measure	Chlorthalidone n=81 participants at risk Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 participants at risk Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Infections and infestations Infection	2.5% 2/81 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	1.3% 1/79 • Number of events 1 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Cardiac disorders Cardiovascular Event	3.7% 3/81 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	6.3% 5/79 • Number of events 7 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Renal Event	1.2% 1/81 • Number of events 1 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	1.3% 1/79 • Number of events 1 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
General disorders Event of Interest	3.7% 3/81 • Number of events 4 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	0.00% 0/79 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
General disorders Other	3.7% 3/81 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	6.3% 5/79 • Number of events 6 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).

Other adverse events

Measure	Chlorthalidone n=81 participants at risk Subjects with stage 4 chronic kidney disease (CKD) and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home blood pressure (BP) results. Chlorthalidone: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)	Placebo n=79 participants at risk Subjects with stage 4 CKD and poorly controlled hypertension confirmed by 24 hour ambulatory blood pressure monitoring will be randomized into two groups, one receiving placebo and one receiving a diuretic called chlorthalidone (12.5 mg at randomization). Doubling of the dose of the diuretic (up to 50 mg) or placebo will occur every 4 weeks if required by home BP results. Placebo: This is a forced-titration study and the study drug or placebo will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Infections and infestations Infection	7.4% 6/81 • Number of events 6 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	12.7% 10/79 • Number of events 10 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Cardiac disorders Cardiovascular Event	2.5% 2/81 • Number of events 2 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	3.8% 3/79 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
General disorders Other	51.9% 42/81 • Number of events 57 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	49.4% 39/79 • Number of events 64 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hypokalemia	9.9% 8/81 • Number of events 10 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	0.00% 0/79 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hypomagnesemia	23.5% 19/81 • Number of events 35 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	16.5% 13/79 • Number of events 26 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hyponatremia	11.1% 9/81 • Number of events 12 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	7.6% 6/79 • Number of events 6 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hypocalcemia	1.2% 1/81 • Number of events 1 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	1.3% 1/79 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hypercalcemia	2.5% 2/81 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	2.5% 2/79 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hyperglycemia	16.0% 13/81 • Number of events 18 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	5.1% 4/79 • Number of events 5 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hyperuricemia	19.8% 16/81 • Number of events 32 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	8.9% 7/79 • Number of events 9 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hyperkalemia	6.2% 5/81 • Number of events 5 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	8.9% 7/79 • Number of events 8 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Hypernatremia	0.00% 0/81 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	1.3% 1/79 • Number of events 1 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Musculoskeletal and connective tissue disorders Acute Gout	2.5% 2/81 • Number of events 2 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	3.8% 3/79 • Number of events 3 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Cardiac disorders Syncope	2.5% 2/81 • Number of events 2 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	1.3% 1/79 • Number of events 1 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Vascular disorders Orthostatic Hypotension	9.9% 8/81 • Number of events 12 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	6.3% 5/79 • Number of events 8 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Cardiac disorders Dizziness	24.7% 20/81 • Number of events 33 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	16.5% 13/79 • Number of events 24 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Vascular disorders Asymptomatic Orthostatic Hypotension	25.9% 21/81 • Number of events 39 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	22.8% 18/79 • Number of events 33 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Renal and urinary disorders Acute Kidney Injury	40.7% 33/81 • Number of events 61 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).	12.7% 10/79 • Number of events 12 • Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).

Additional Information

Dr. Rajiv Agarwal

Indiana University

Phone: 3179882241

Email: ragarwal@iu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place