6/28/23, 12:11 AM CLICK Pathway Feedback Search Clinical Topics Home Studies CLICK CLICK Disease Disease Chronic kidney disease Hypertension 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 N = 160 77.2% male 160 patients (36 female, 124 male) Inclusion criteria: patients with stage 4 CKD and poorly controlled hypertension Key exclusion criteria: 24-hour ambulatory systolic BP 160 mmHg or diastolic BP 100 mmHg; history of stroke or myocardial infarction; 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 24-hour ambulatory systolic blood pressure reduction at week 12 11.0 mmHg 11 https://web.pathway.md/studies/recUw7lUATGAofJEt 1/2 6/28/23, 12:11 AM CLICK Pathway 8.3 mmHg 5.5 mmHg 2.8 mmHg Significant increase 0.5 0.0 mmHg Chlorthalidone Placebo Significant increase in 24-hour ambulatory systolic BP reduction 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) Significant increase in N-terminal pro-B-type natriuretic peptide reduction 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 m vs. 0.5 mL/min/1.73 m ; AD 2.2 mL/min/1.73 m , 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 a 24-hour ambulatory systolic BP reduction 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 https://web.pathway.md/studies/recUw7lUATGAofJEt 2/2