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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Perindopril plus Amlodipine
* Drug: Perindopril plus Hydrochlorothiazide
* Drug: Amlodipine plus Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Perindopril plus Amlodipine at a dose of 4mg/5mg once daily for two months and 8mg/10mg once daily for the remaining four months. | Drug: Perindopril plus Hydrochlorothiazide<br>* Group 2<br>Drug: Amlodipine plus Hydrochlorothiazide<br>* Group 3<br>|
| Active Comparator: 2<br>Perindopril Plus Hydrochlorothiazide at a dose of 4mg/12.5mg and 8mg/25mg once daily for the remaining four months. | Drug: Perindopril plus Amlodipine<br>* Group 1<br>Drug: Amlodipine plus Hydrochlorothiazide<br>* Group 3<br>|
| Active Comparator: 3<br>Amlodipine plus Hydrochlorothiazide 5mg/12.5mg for two months and 10mg/25mg for the remaining four months. | Drug: Perindopril plus Amlodipine<br>* Group 1<br>Drug: Perindopril plus Hydrochlorothiazide<br>* Group 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ambulatory blood pressure | Change in ambulatory systolic blood pressure measurement from baseline to 6 months from will be determined. | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of ambulatory diastolic blood pressure | Change in 24 hour ambulatory diastolic blood pressure between randomisation and 6 months | six months | 
| Clinic systolic and diastolic blood pressure | Change in clinic systolic and diastolic blood pressure will be difference in values between randomisation and 6 months | Six months | 
| Night time and day time blood pressure | Change in daytime and night time blood pressure | Six months | 
| Blood pressure control | change in BP variability measured will be measured by ambulatory blood pressure | Six months | 
| Blood pressure control | Proportion of patients who achieve BP control (defined as clinic BP < 140/90 mmHg) after 6 months | Two months and six months | 
| Response to study medications | Proportion of responders (defined as clinic BP reduction > 20mmHg SBP and >10 mmHg DBP) from randomisation to 6 months | Two months and six months | 
| Change in values of micro- and macro-albuminuria | Change in micro- and macro-albuminuria will be measured from randomisation to 6 months | Six months | 
| Fasting blood sugar variation | Change in fasting blood sugar which will be from randomisation to 6 months | Six months | 
| Fasting lipid profile variation | Change in fasting lipid profile between from randomisation to 6 months | Six months |