A Pilot Study of Chlorthalidone Among Patients With Poorly Controlled Hypertension and CKD

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01750294
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Duration (Months): 12
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

It is estimated that in the United States there are approximately 8 million individuals with moderate to severe chronic kidney disease (CKD), not on dialysis. Volume expansion plays an important role in the pathogenesis of hypertension in patients with CKD. For this pilot study, the investigators hypothesize that administration of chlorthalidone among patients with moderate to severe CKD will improve blood pressure (BP).

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease; Poorly-Controlled Hypertension	Drug: Chlorthalidone	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Outcome Measures

Primary Outcome Measures

1. Change of Systolic Ambulatory Blood Pressure From Baseline to 12 Weeks [Baseline and 12 weeks after intervention]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age greater than 18 years.

• Estimated glomerular filtration rate (eGFR) ≤ 45 ml/min/1.73m2 but ≥20 mL/min/1.73m2.

• Poorly controlled blood pressure by 24-hour ambulatory blood pressure (BP) monitoring.

• Treated hypertension: 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.

Exclusion Criteria:

• Use of thiazide or thiazide-like drugs in the previous 3 months.

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

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

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

• Vascular event such as myocardial infarction, heart failure hospitalization, or stroke within 3 months prior to randomization.

• 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).

• Known hypersensitivity to thiazide or sulfa drugs.

• Organ transplant recipient or therapy with immunosuppressive agents. Nasal or inhaled corticosteroids will be permitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Richard L. Roudebush VAMC	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University

Investigators

• Principal Investigator: Rajiv Agarwal, MD FASN FAHA, Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indiana University
• ClinicalTrials.gov Identifier: NCT01750294
• Other Study ID Numbers: 1206009002; 1206009002
• First Posted: Dec 17, 2012
• Last Update Posted: Jun 13, 2016
• Last Verified: May 1, 2016

• Keywords provided by Indiana University: hypertension; kidney disease
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hypertension; Chlorthalidone

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the VA Medical Center from Sept. 18, 2012 - May 15, 2013. Eligible subjects were ≥ 18 years of age with estimated glomerular filtration rate ≤ 45 but > 20 mL/min/1.73m2. The study initially recruited subjects with resistant hypertension but was amended to include those with poorly controlled but treated hypertension.
Pre-assignment Detail	Prior to assignment, participants completed home blood pressure monitoring, ambulatory blood pressure monitoring, and a two-week run-in period, during which all subjects received a standard anti-hypertensive regimen based on the existing regimen of the subject.

Arm/Group Title	Chlorthalidone
Arm/Group Description	Open-label, forced-titration of Chlorthalidone (25mg/day at baseline)
Period Title: Overall Study
STARTED	14
COMPLETED	12
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Chlorthalidone
Arm/Group Description	Open-label, forced-titration of Chlorthalidone (25mg/day at baseline)
Overall Participants	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.5 (10.2)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	14 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 57.1%
White	6 42.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Chronic Kidney Disease (CKD) Stage (participants) [Number]
Stage 3B	4 28.6%
Stage 4	8 57.1%
Stage 5	2 14.3%
Estimated GFR (mL/min/1.73m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min/1.73m2]	26.8 (8.8)

Outcome Measures

1. Primary Outcome

Title	Change of Systolic Ambulatory Blood Pressure From Baseline to 12 Weeks
Time Frame	Baseline and 12 weeks after intervention

Outcome Measure Data

Analysis Population Description

Intention to treat analysis (includes completers and non-completers)

Arm/Group Title	Chlorthalidone
Arm/Group Description	Open-label, forced-titration of Chlorthalidone (25mg/day at baseline)
Measure Participants	14
Mean (Standard Deviation) [mmHg]	-10.5 (4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chlorthalidone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments	a = 0.05
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Baseline (week 0) through study completion (week 12)
Arm/Group Title	Chlorthalidone
Arm/Group Description	Open-label, forced-titration of Chlorthalidone (25mg/day at baseline)
All Cause Mortality
	Chlorthalidone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Chlorthalidone
	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)
Nervous system disorders
New-onset ischemic stroke	1/14 (7.1%)	1
Syncope	1/14 (7.1%)	2
Renal and urinary disorders
Elective kidney biopsy	1/14 (7.1%)	1
Vascular disorders
Hypotension	1/14 (7.1%)	2
Other (Not Including Serious) Adverse Events
	Chlorthalidone
	Affected / at Risk (%)	# Events
Total	7/14 (50%)
Gastrointestinal disorders
Constipation	1/14 (7.1%)	1
Investigations
Transient elevations of serum creatinine	3/14 (21.4%)	3
Metabolism and nutrition disorders
Hypokalemia	4/14 (28.6%)	4
Hyperuricemia	4/14 (28.6%)	4
Hyponatremia	3/14 (21.4%)	3
Hyperglycemia	1/14 (7.1%)	1
Nervous system disorders
Dizziness	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

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.