Efficacy and safety of a single-pill versus free combination of perindopril/indapamide/amlodipine: a multicenter, randomized, double-blind study in Chinese patients with hypertension

J Hypertens. 2024 Aug 1;42(8):1373-1381. doi: 10.1097/HJH.0000000000003741. Epub 2024 Apr 24.

Abstract

Background: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals.

Methods: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM).

Results: A total of 532 patients were randomized: Per/Ind/Aml ( n = 262) and Per/Ind + Aml ( n = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ± 14.46 mmHg Per/Ind/Aml versus -14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated.

Conclusions: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Aged
  • Amlodipine* / administration & dosage
  • Amlodipine* / adverse effects
  • Antihypertensive Agents* / administration & dosage
  • Antihypertensive Agents* / adverse effects
  • Antihypertensive Agents* / therapeutic use
  • Blood Pressure / drug effects
  • China
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • East Asian People
  • Female
  • Humans
  • Hypertension* / drug therapy
  • Hypertension* / physiopathology
  • Indapamide* / administration & dosage
  • Indapamide* / therapeutic use
  • Male
  • Middle Aged
  • Perindopril* / administration & dosage
  • Perindopril* / therapeutic use
  • Treatment Outcome

Substances

  • Amlodipine
  • Indapamide
  • Perindopril
  • Antihypertensive Agents
  • Drug Combinations