CLICK: Chlorthalidone in Chronic Kidney Disease

• Sponsor: Indiana University (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02841280
• Collaborator: (none)
• Enrollment: 160
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 91
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

It is estimated that in the United States there are approximately 8 million individuals who have moderate to severe chronic kidney disease (CKD). Among them hypertension is common and is often poorly controlled due to an expanded volume state; diuretics are frequently prescribed. Loop diuretics are potent and effective in lowering blood pressure (BP) but their use is associated with acute kidney injury. Thiazide diuretics, on the other hand, are less potent, their use may be associated with less acute kidney injury, but as yet there are no firm data to support that thiazide diuretic therapy can improve BP among subjects with advanced CKD. The investigators found 13 studies on the use of thiazide diuretics in advanced CKD either alone or in combination with loop diuretics and concluded that thiazides may be useful. Thiazides cause a negative Na balance, increase Na excretion by 10-15% and weight loss by 1-2 kg in observational studies. Observational data show that thiazides lead to an improvement in seated clinic BP of about 10-15 mmHg systolic and 5-10 mmHg diastolic whereas randomized trials show about a 15 mmHg reduction in mean BP. Randomized trials had only between 7 and 23 subjects each; accordingly, larger studies are needed to evaluate their safety and efficacy in moderate to advanced CKD.

Condition or Disease	Intervention/Treatment	Phase
Renal Insufficiency, Chronic; Hypertension	Drug: Chlorthalidone; Drug: Placebo	Phase 2

Detailed Description

This is a placebo-controlled, double-blind, randomized controlled trial of chlorthalidone (CTD) in patients with CKD and poorly controlled hypertension

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Apr 1, 2021
• Anticipated Study Completion Date: Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Chlorthalidone; This is a forced-titration study and the study drug will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg)
Placebo Comparator: 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.	Drug: Placebo; This is a forced-titration study and placebo will be increased if goal BP is not achieved.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo. [Baseline to 12 weeks]

Secondary Outcome Measures

1. Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo [Baseline to 12 weeks]

2. 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. [Baseline to 12 weeks]

3. 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. [Baseline to 12 weeks]

4. 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. [Baseline to 12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age greater than 18 years.

2. Calculated glomerular filtration rate (GFR) by 4-component Modification of Diet in Renal Disease (MDRD) formula < 30 ml/min/1.73m2 but ≥15 mL/min/1.73m2. The hospital laboratory uses isotope dilution mass spectrometry (IDMS) calibrated creatinine and the appropriate formula is used to estimate GFR.

3. Hypertension. This is defined as BP of either ≥130 systolic or ≥80 mmHg by 24-hour ambulatory BP monitoring.

4. Treatment with antihypertensive drugs: This would require the use of at least one antihypertensive drug. One of the drugs should be either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). If these are contraindicated then use of a beta-blocker is required prior to randomization.

Exclusion Criteria:

1. Use of thiazide or thiazide-like drugs in the previous 12 weeks.

2. Use of furosemide in a dose >200 mg/d.

3. BP of either ≥160 systolic or ≥100 mmHg by 24-hour ambulatory BP monitoring.

4. Expected to receive renal replacement therapy within the next 3 months.

5. Myocardial infarction, heart failure hospitalization, or stroke ≤3 months prior to randomization.

6. Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception (oral contraceptives. condoms and diaphragms will be considered reliable).

7. Known hypersensitivity to thiazide or sulfa drugs.

8. Organ transplant recipient or therapy with immunosuppressive agents.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University School of Medicine, Division of Nephrology	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University

Investigators

• Principal Investigator: Rajiv Agarwal, MD, Indiana University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 14, 2019

More Information

Publications

None provided.

• Responsible Party: Rajiv Agarwal, Professor of Medicine, Indiana University
• ClinicalTrials.gov Identifier: NCT02841280
• Other Study ID Numbers: 1507540384
• First Posted: Jul 22, 2016
• Last Update Posted: Mar 31, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Renal Insufficiency; Renal Insufficiency, Chronic; Chlorthalidone

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Chlorthalidone	Placebo
Arm/Group Description	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)	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)
Period Title: Overall Study
STARTED	81	79
COMPLETED	67	73
NOT COMPLETED	14	6

Baseline Characteristics

Arm/Group Title	Chlorthalidone	Placebo	Total
Arm/Group Description	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)	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 of all reporting groups
Overall Participants	81	79	160
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	34 42%	33 41.8%	67 41.9%
>=65 years	47 58%	46 58.2%	93 58.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.2 (10.8)	66.7 (10.8)	66.4 (10.8)
Sex: Female, Male (Count of Participants)
Female	19 23.5%	17 21.5%	36 22.5%
Male	62 76.5%	62 78.5%	124 77.5%
Race/Ethnicity, Customized (Count of Participants)
White	46 56.8%	47 59.5%	93 58.1%
Black	32 39.5%	32 40.5%	64 40%
Asian	2 2.5%	0 0%	2 1.3%
Hispanic	1 1.2%	0 0%	1 0.6%
Region of Enrollment (participants) [Number]
United States	81 100%	79 100%	160 100%
Medical History of Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	60 74.1%	61 77.2%	121 75.6%
Cause of Chronic Kidney Disease (Count of Participants)
Diabetes	42 51.9%	42 53.2%	84 52.5%
Hypertension	26 32.1%	26 32.9%	52 32.5%
Glomerulonephritis	3 3.7%	5 6.3%	8 5%
Obstructive Uropathy	3 3.7%	2 2.5%	5 3.1%
Polycystic Kidney Disease	1 1.2%	1 1.3%	2 1.3%
Other	6 7.4%	3 3.8%	9 5.6%
Current Smoking (Count of Participants)
Count of Participants [Participants]	21 25.9%	19 24.1%	40 25%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	171.7 (11.3)	173.0 (8.6)	172.3 (10.1)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	97.4 (23.6)	95.8 (23.5)	96.6 (23.6)
Body-Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	33.0 (7.0)	32.0 (7.4)	32.5 (7.2)
Hip Circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	115.9 (14.9)	114.6 (15.0)	115.3 (14.9)
Waist Circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	115.3 (17.0)	115.4 (16.6)	115.3 (16.8)
Waist-to-Hip Ratio (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	1.011 (0.078)	0.998 (0.074)	1.005 (0.076)
Systolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	141.2 (15.1)	138.7 (16.0)	140.0 (15.6)
Diastolic Blood Pressure (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	69.2 (12.3)	67.9 (13.9)	68.6 (13.1)
Pulse Rate (beats/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [beats/min]	66.5 (11.7)	64.3 (11.1)	65.4 (11.4)
Estimated Glomerular Filtration Rate (ml/min/1.73 m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/min/1.73 m^2]	23.5 (4.2)	22.8 (4.2)	23.2 (4.2)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chlorthalidone	Placebo
Arm/Group Description	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)	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)
Measure Participants	81	79
Mean (95% Confidence Interval) [mm Hg]	-11.0	-0.5

2. Secondary Outcome

Title	Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chlorthalidone	Placebo
Arm/Group Description	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)	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)
Measure Participants	81	79
Percent change in albuminuria 4 weeks from baseline in UACR	-41	-7
Percent change in albuminuria 8 weeks from baseline in UACR	-45	-3
Percent change in albuminuria 12 weeks from baseline in UACR	-52	-4

3. Secondary Outcome

Title	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chlorthalidone	Placebo
Arm/Group Description	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)	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)
Measure Participants	81	79
Percent change 4 weeks from baseline in aldosterone	57	16
Percent change 8 weeks from baseline in aldosterone	65	12
Percent change 12 weeks from baseline in aldosterone	52	8
Percent change 4 weeks from baseline in renin	57	14
Percent change 8 weeks from baseline in renin	67	5
Percent change 12 weeks from baseline in renin	64	15

4. Secondary Outcome

Title	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chlorthalidone	Placebo
Arm/Group Description	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)	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)
Measure Participants	81	79
Percent change from 4 weeks from baseline in NTproBNP	-25	-14
Percent change from 8 weeks from baseline in NTproBNP	-32	5
Percent change from 12 weeks from baseline in NTproBNP	-30	-11

5. Secondary Outcome

Title	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.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chlorthalidone	Placebo
Arm/Group Description	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)	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)
Measure Participants	81	79
Change in body volume 4 weeks from baseline	-1.1	0.2
Change in body volume 8 weeks from baseline	-1.7	0.3
Change in body volume 12 weeks from baseline	-2	0.3

Adverse Events

Time Frame	Adverse events were recorded during the period from the time of randomization to the discontinuation of the regimen (12 weeks).
Arm/Group Title	Chlorthalidone		Placebo
Arm/Group Description	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)		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)
All Cause Mortality
	Chlorthalidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/81 (1.2%)		0/79 (0%)
Serious Adverse Events
	Chlorthalidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/81 (9.9%)		11/79 (13.9%)
Cardiac disorders
Cardiovascular Event	3/81 (3.7%)	3	5/79 (6.3%)	7
General disorders
Event of Interest	3/81 (3.7%)	4	0/79 (0%)	0
Other	3/81 (3.7%)	3	5/79 (6.3%)	6
Infections and infestations
Infection	2/81 (2.5%)	3	1/79 (1.3%)	1
Renal and urinary disorders
Renal Event	1/81 (1.2%)	1	1/79 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Chlorthalidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/81 (91.4%)		68/79 (86.1%)
Cardiac disorders
Cardiovascular Event	2/81 (2.5%)	2	3/79 (3.8%)	3
Syncope	2/81 (2.5%)	2	1/79 (1.3%)	1
Dizziness	20/81 (24.7%)	33	13/79 (16.5%)	24
General disorders
Other	42/81 (51.9%)	57	39/79 (49.4%)	64
Infections and infestations
Infection	6/81 (7.4%)	6	10/79 (12.7%)	10
Musculoskeletal and connective tissue disorders
Acute Gout	2/81 (2.5%)	2	3/79 (3.8%)	3
Renal and urinary disorders
Hypokalemia	8/81 (9.9%)	10	0/79 (0%)	0
Hypomagnesemia	19/81 (23.5%)	35	13/79 (16.5%)	26
Hyponatremia	9/81 (11.1%)	12	6/79 (7.6%)	6
Hypocalcemia	1/81 (1.2%)	1	1/79 (1.3%)	3
Hypercalcemia	2/81 (2.5%)	3	2/79 (2.5%)	3
Hyperglycemia	13/81 (16%)	18	4/79 (5.1%)	5
Hyperuricemia	16/81 (19.8%)	32	7/79 (8.9%)	9
Hyperkalemia	5/81 (6.2%)	5	7/79 (8.9%)	8
Hypernatremia	0/81 (0%)	0	1/79 (1.3%)	1
Acute Kidney Injury	33/81 (40.7%)	61	10/79 (12.7%)	12
Vascular disorders
Orthostatic Hypotension	8/81 (9.9%)	12	5/79 (6.3%)	8
Asymptomatic Orthostatic Hypotension	21/81 (25.9%)	39	18/79 (22.8%)	33

Limitations/Caveats

The trial was relatively small and had an underrepresentation of women (36 of 160 patients [22%] were women). In addition, very few patients were Asian or Hispanic.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.