The creole study is a 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.

The CREOLE trial will be performed at ten investigational sites in six countries in Sub-Saharan Africa which include Cameroun, Kenya, Mozambique, Nigeria, South Africa and Uganda. Subjects will be randomised to one of three treatments which are Perindopril plus Amlodipine or Perindopril plus Hydrochlorothiazide or Amlodipine plus Hydrochlorothiazide.Patients will commence treatment at a starting dose of Amlodipine plus Hydrochlorothiazide 5/12.5 mg or Amlodipine plus Perindopril 5/4 mg or Perindopril/Hydrochlorothiazide 4/12.5 mg. These doses will increase at the two months visit, to Amlodipine/Hydrochlorothiazide 10/25 mg or AmlodipinePperindopril 10/8mg or Perindopril/Hydrochlorothiazide 8/25 mg.

The patients will have ambulatory blood pressure monitoring at randomization and at six months and office blood pressure measurements at randomization and at two-month, 4-month and six-month visits.The overall aim is to discover the best combination of front-line anti-hypertensive medications for black patients residing in sub-Saharan Africa.

Inclusion Criteria:

• Patients with Sitting SBP ≥140 mm Hg and < 160 mmHg on one antihypertensive agen or
• Sitting SBP ≥ 150 mm Hg and < 180 mm Hg on no antihypertensive treatment.

Exclusion Criteria:

• Congestive heart failure (clinically defined).
• Serum creatinine levels greater than 170 µmol/l or estimated glomerular filtration rate (eGFR) < 30 ml/min.
• History of coronary heart disease (i.e., chronic stable angina, myocardial infarction or acute coronary syndrome).
• History of a stroke or other cerebrovascular accident (i.e. transient ischaemic attack or reversible ischaemic neurological deficit).
• Known or suspected secondary hypertension.
• Any other concomitant illness, physical or mental impairment that could interfere with the effective conduct of the study.
• Pregnancy or those of child-bearing age who are not taking reliable contraception.
• Patients with a history of intolerance to any of the study medications for example angioedema or dry cough with angiotensin converting enzyme inhibitors.
• Patients on maximum dose of any of the study medications as monotherapy (i.e. amlodipine 10 mg/day or hydrochlorothiazide 25 mg/day or perindopril 8 mg/day)
• Gout.
• Serum potassium < 3.5mmol/L at screening.