CLICK
Trial question
What is the role of chlorthalidone in patients with advanced CKD and poorly controlled hypertension?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
22.8% female
77.2% male
N = 160
160 patients (36 female, 124 male).
Inclusion criteria: patients with stage 4 CKD and poorly controlled hypertension.
Key exclusion criteria: 24-hour ambulatory SBP ≥ 160 mmHg or DBP ≥ 100 mmHg; history of stroke or MI; receipt of high-dose loop diuretics; receipt of thiazide or thiazide-like drugs within 12 weeks.
Interventions
N=81 chlorthalidone (initial dose of 12.5 mg/day, doubled every 4 weeks to a maximum dose of 50 mg/day, for 12 weeks).
N=79 placebo (matching placebo for 12 weeks).
Primary outcome
Reduction in 24-hour ambulatory systolic blood pressure at week 12
11 mmHg
0.5 mmHg
11.0 mmHg
8.3 mmHg
5.5 mmHg
2.8 mmHg
0.0 mmHg
Chlorthalidone
Placebo
Significant
increase ▲
Significantly greater reduction in 24-hour ambulatory SBP at week 12 (11 mmHg vs. 0.5 mmHg; AD 10.5 mmHg, 95% CI 14.6 to 6.4).
Secondary outcomes
Significant increase in urine albumin/creatinine ratio reduction at week 12 (52% vs. 4%; AD 50%, 95% CI 60 to 37).
Significantly greater reduction in N-terminal pro-BNP at week 12 (30% vs. 11%; AD 21%, 95% CI 35 to 4).
Significant increase in eGFR improvement at week 12 (2.7 mL/min/1.73 m² vs. 0.5 mL/min/1.73 m²; AD 2.2 mL/min/1.73 m², 95% CI 3.3 to 1).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In patients with stage 4 CKD and poorly controlled hypertension, chlorthalidone was superior to placebo with respect to reduction in 24-hour ambulatory SBP at week 12.
Reference
Rajiv Agarwal, Arjun D Sinha, Andrew E Cramer et al. Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease. N Engl J Med. 2021 Dec 30;385(27):2507-2519.
Open reference URL