Clinical trial NCT02742467: Comparison of Three Combination Therapies in Lowering Blood Pressure in Black Africans
Official title: Comparison of Three Combination Therapies in Lowering Blood Pressure in Black Africans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Lead sponsor: University of Abuja
Sponsor class: OTHER
Collaborators: name: Imperial College London
name: University of Cape Town
name: Hôpital Edouard Herriot
name: University of Nairobi
name: University College Hospital, Ibadan
name: Hospital General De Douala
name: Mulago Hospital, Uganda
First posted: 2016-04-19
Enrollment: 702
Sex: ALL
Minimum age (years): 30
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ambulatory blood pressure
timeFrame: six months
Secondary outcomes:
measure: Assessment of ambulatory diastolic blood pressure
timeFrame: six months
measure: Clinic systolic and diastolic blood pressure
timeFrame: Six months
measure: Night time and day time blood pressure
timeFrame: Six months
measure: Blood pressure control
timeFrame: Six months
measure: Blood pressure control
timeFrame: Two months and six months
measure: Response to study medications
timeFrame: Two months and six months
measure: Change in values of micro- and macro-albuminuria
timeFrame: Six months
measure: Fasting blood sugar variation
timeFrame: Six months
measure: Fasting lipid profile variation
timeFrame: Six months
Other outcomes:
Locations:
city: Abuja
country: Nigeria
facility: University of Abuja Teaching Hospital
state: Federal Capital Territory
Study officials:
affiliation: Imperial College London
name: Neil Poulter, MD, MSc
role: STUDY_DIRECTOR
affiliation: University of Cape Town
name: Bongani Mayosi, DPhil
role: STUDY_CHAIR
References:
citation: Ingabire PM, Ojji DB, Rayner B, Ogola E, Damasceno A, Jones E, Dzudie A, Ogah OS, Poulter N, Sani MU, Barasa FA, Shedul G, Mukisa J, Mukunya D, Wandera B, Batte C, Kayima J, Pandie S, Mondo CK; CREOLE Study Investigators. High prevalence of non-dipping patterns among Black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial. BMC Cardiovasc Disord. 2021 May 22;21(1):254. doi: 10.1186/s12872-021-02074-7.
citation: Ojji DB, Mayosi B, Francis V, Badri M, Cornelius V, Smythe W, Kramer N, Barasa F, Damasceno A, Dzudie A, Jones E, Mondo C, Ogah O, Ogola E, Sani MU, Shedul GL, Shedul G, Rayner B, Okpechi IG, Sliwa K, Poulter N; CREOLE Study Investigators. Comparison of Dual Therapies for Lowering Blood Pressure in Black Africans. N Engl J Med. 2019 Jun 20;380(25):2429-2439. doi: 10.1056/NEJMoa1901113. Epub 2019 Mar 18.