CREOLE

Clinical Trial Details

Comparison of Three Combination Therapies in Lowering Blood Pressure in Black Africans

A Multi-centre, multinational, randomised single-blind, parallel group, three-armed superiority trial which is aimed at comparing the efficacy of three "free" combinations of two anti-hypertensive agents on 24 hour ambulatory systolic blood pressure (ASBP) in black African hypertensive patients.

Key Findings

For black sub-Saharan African patients, blood pressure was lowered better with amlodipine (a long-acting calcium channel blocker) + either hydrochlorothiazide or perindopril than with perindopril + hydrochlorothiazide (no amlodipine).

CREOLE Trial Principal Investigator

Dike Ojii, MBBS, PhD provides and overview of the CREOLE trial and resistant hypertension in the sub-Saharan African community.


CREOLE Study Data
Mean between-group difference change from baseline -systolicP
Amlodipine + HCTZ vs perindopril + HCTZ−3.14 mm Hg0.03
Amlodipine + perindopril vs perindopril + HCTZ−3.00 mm Hg0.04
Amlodipine + HCTZ vs amlodipine + perindopril−0.14 mm Hg0.92

Purpose: This trial examines the efficacy of 3 combinations of 2 anti-hypertensive medications on 24-hour ambulatory systolic BP (ASBP) to determine the best combination for black sub-Saharan African patients with hypertension.

Trial design: Phase 4; 728 hypertensive black sub- Saharan African patients with hypertension; mean age 51 years; 63% women. Multi-center (10 sires), multinational, single-blinded, parallel, randomized, 3-arm superiority trial.  1. perindopril + amlodipine ( 5/4 mg), vs 2. perindopril + hydrochlorothiazide (4/12.5 mg), vs 3. amlodipine plus hydrochlorothiazide (5/12.5 mg).  Dose is increased at 2 months to perindopril + amlodipine (10/8mg), vs perindopril + hydrochlorothiazide (8/25 mg), vs amlodipine plus hydrochlorothiazide (10/25 mg).  Ambulatory BP checked at randomization and 6 months.  Office BP checked at randomization, 2, 4, and 6 months.

Primary endpoints: Change in ambulatory systolic from randomization to 6 months.

Results: For black sub-Saharan African patients, blood pressure was lowered better with amlodipine (a long-acting calcium channel blocker) + either hydrochlorothiazide or perindopril than with perindopril + hydrochlorothiazide (no amlodipine).

Background

This trial examines the efficacy of 3 combinations of 2 anti-hypertensive medications on 24-hour ambulatory systolic BP (ASBP) to determine the best combination for black sub-Saharan African patients with hypertension.

Trial design: Phase 4. 6 sub-Saharan countries, single-blinded, parallel, randomized, 3-arm trial. Perindopril + amlodipine (5/4 mg), vs perindopril + hydrochlorothiazide (4/12.5 mg), vs amlodipine plus hydrochlorothiazide (5/12.5 mg). Dose is increased at 2 months to perindopril + amlodipine (10/8mg), vs perindopril + hydrochlorothiazide (8/25 mg), vs amlodipine plus hydrochlorothiazide (10/25 mg). Ambulatory BP checked at randomization and 6 months. Office BP checked at randomization, 2, 4, and 6 months.

Trial population: 728 hypertensive black sub-Saharan African patients with hypertension; mean age 51 years; 63% women.

Primary endpoints: change in ambulatory systolic from randomization to 6 months.

Secondary endpoints::

  • Change in 24-hour ambulatory diastolic BP from randomization to 6 months
  • Change in clinic systolic and diastolic BP from randomization to 6 months
  • Night and day BP over 6 months
  • BP control over 6 months
  • Response to study medications over 6 months; responder = > 20mmHg SBP reduction in clinic BP and >10 mmHg DBP

Results:

Primary endpoints: mean between-group difference change from baseline

  • Amlodipine+ HCTZ vs perindopril+ HCTZ 
    −3.14 mm Hg; 95% confidence interval [CI], −5.90 to −0.38; P=0.03
     
  • Amlodipine+ perindopril vs perindopril+ HCTZ
    −3.00 mm Hg; 95% confidence interval [CI], −5.8 to −0.20; P = 0.04
     
  • Amlodipine+ HCTZ vs amlodipine + perindopril
    −0.14 mm Hg; 95% confidence interval [CI], −2.90 to 2.61; P=0.92
     

Investigators:
Study Director: Neil Poulter, MD, MSc, Imperial College London
Study Chair: Bongani Mayosi, Dphil, University of Cape Town

 

Sponsors and collaborators:
University of Abuja
Imperial College London
University of Cape Town
Hôpital Edouard Herriot
University of Nairobi
University College Hospital, Ibadan
Hospital General De Douala
Mulago Hospital, Uganda

References:

Related Science:

Key Words
Hypertension, amlodipine, hydrochlorothiazide, perindopril, antihypertensive agents, calcium channel blockers, membrane transport modulators, molecular mechanisms of pharmacological action, calcium-regulating hormones and agents, vasodilator agents, diuretics, angiotensin-converting enzyme inhibitors, protease inhibitors, enzyme inhibitors

Related Clinical Topics
HTN, special populations, drug discovery

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