Phase 2
N=160
Chlorthalidone in Chronic Kidney Disease
Renal Insufficiency, Chronic · Hypertension
Bottom Line
View on ClinicalTrials.gov: NCT02841280 ↗Enrolled (actual)
160
Serious AEs
11.9%
Results posted
Mar 2022
Primary outcome: Primary: Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo. — -11.0; -0.5 mm Hg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Chlorthalidone (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Indiana University
- Primary completion
- Apr 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to 12 Weeks in Systolic Ambulatory Blood Pressure in the Chlorthalidone Group Compared to Placebo. |
-11.0; -0.5 | — |
| SECONDARY Changes in Albuminuria From Baseline at Each 4 Week Visit in the Log Transformed Albumin/Creatinine Ratio in the Chlorthalidone Group Compared to Placebo |
-41; -7; -45; -3; -52; -4 | — |
| SECONDARY 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. |
57; 16; 65; 12; 52; 8 | — |
| SECONDARY 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. |
-25; -14; -32; 5; -30; -11 | — |
| SECONDARY 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. |
-1.1; 0.2; -1.7; 0.3; -2; 0.3 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Age greater than 18 years.
- Calculated glomerular filtration rate (GFR) by 4-component Modification of Diet in Renal Disease (MDRD) formula 200 mg/d.
- 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.
- Myocardial infarction, heart failure hospitalization, or stroke ≤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.
Data sourced from ClinicalTrials.gov (NCT02841280). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.