Comparison of Three Combination Therapies in Lowering Blood Pressure in Black Africans (Creole)

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Perindopril plus Hydrochlorothiazide; Drug: Amlodipine plus Hydrochlorothiazide; Drug: Perindopril plus Amlodipine

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.

• Study Type: Interventional
• Enrollment (Actual): 702
• Phase: Phase 4

Contacts and Locations

Study Locations

• Nigeria
  • Federal Capital Territory
    • Abuja, Federal Capital Territory, Nigeria, 90001
      • University of Abuja Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Abuja
• Collaborators: Imperial College London; University College Hospital, Ibadan; University of Nairobi; University of Cape Town; Hôpital Edouard Herriot; Mulago Hospital, Uganda; Hospital General De Douala
• Investigators: Study Director: Neil Poulter, MD, MSc, Imperial College London; Study Chair: Bongani Mayosi, DPhil, University of Cape Town

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2017
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: April 14, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimate): April 19, 2016

Study Record Updates

• Last Update Posted (Actual): August 24, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Sodium Chloride Symporter Inhibitors; Amlodipine; Hydrochlorothiazide; Perindopril
• Other Study ID Numbers: Project8264

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No