Plain English Summary
Background and study aims
Hypertension (high blood pressure) is the leading cause of disability and death in the world. It is a particular problem in Africa, where genetic causes of salt and water retention make hypertension more common, and make blood pressure control more difficult. In many cases, the exact cause of hypertension is not known, which can make finding the most appropriate treatment more difficult. By testing the blood for specific chemicals - renin (a kidney enzyme) and aldosterone (a hormone produced by the adrenal glands, located on top of the kidney) - it is possible to identify which treatments would be most effective based on the actual cause of the hypertension. The aim of this study is to look at the effectiveness of individualized therapy based on the physiological cause of the hypertension as determined from the plasma renin and aldosterone testing.
Who can participate?
Adult patients with resistant hypertension (blood pressure above 160/90 despite three medications) who are attending one of the three hypertension clinics participating in the study.
What does the study involve?
Patients are randomly allocated to one of two groups. Those in the first group continue to receive usual care according to the consensus guidelines of the country in which the clinic is located. Those in the second group take part in a new strategy of care based on finding the underlying physiological process that is causing the high blood pressure. This is done by taking a sample of blood and measuring levels of renin, and aldosterone. The results of these tests are then analysed and used to choose the most appropriate therapy. Participants in both groups are followed up after one year to find out if their blood pressure control has improved.
What are the possible benefits and risks of participating?
It is anticipated that the patients who take part in the new strategy will benefit from better blood pressure control. There are no notable risks involved with taking part in this study.
Where is the study run from?
1. Ladoke Akintola University of Technology Teaching Hospital (Nigeria)
2. Groote Schuur Hospital (South Africa)
3. Nakuru County Referral Hospital (Kenya)
When is study starting and how long is it expected to run for?
September 2013 to June 2016
Who is funding the study?
Grand Challenges Canada (Canada)
Who is the main contact?
Dr. J. David Spence
dspence@robarts.ca
Trial website
Contact information
Type
Scientific
Primary contact
Prof J. David Spence
ORCID ID
http://orcid.org/0000-0001-7478-1098
Contact details
Robarts Research Institute
Western University
1400 Western Road
London
N6G 2V4
Canada
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
01
Study information
Scientific title
Physiologically individualized therapy for resistant hypertension in Africa
Acronym
Study hypothesis
Individualized therapy for resistant hypertension will improve blood pressure control compared to usual therapy.
Ethics approval
1. Human Research Ethics Board of Western University, 20/08/2013 (renewal date: 10/11/2014), ref: 103876
2. University of Cape Town Faculty of Health Sciences Human Research Ethics Committee, 04/04/2013, ref: 169/2013
3. Ethical Committee Ladoke Akintola University of Technology Teaching Hospital, 20/06/2013, ref: LTH/OGB/Ec/2013/003
4. Egerton University Research Ethics Board, 22/07/2013, ref: EUIDVRE/009
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
No participant information sheet available
Condition
Resistant hypertension
Intervention
On the first study visit, participants have blood samples taken for measurement of plasma renin and aldosterone using kits provided by Diagnostics Biochem Canada Inc, and a sample of blood to be sent for DNA extraction and Sanger sequencing to identify genetic factors that may cause salt and water retention.
Patients are randomized using random numbers generated in SPSS, to either the usual care group (in which the plasma renin and aldosterone results are blinded to the physician and the patient) or the physiologically individualized treatment group, in which the plasma renin and aldosterone levels are used to choose the most appropriate therapy. The algorithm used to interpret the plasma renin and aldosterone levels and choose appropriate therapy was described in 2012 (Spence JD. Lessons from Africa: the importance of measuring plasma renin and aldosterone in resistant hypertension. Can J Cardiol. 2012 May;28(3):254-7. PMID: 22289470).
Participants in both groups are followed up for one year in the hypertension clinic, with visits scheduled according to the usual routine in each clinic.
Intervention type
Drug
Phase
Phase III
Drug names
Primary outcome measure
Blood pressure control, defined as a systolic pressure <140 mmHg and Diastolic Control is defined as a diastolic pressure <90, is measured using an automated blood pressure device at baseline and one year.
Secondary outcome measures
Nucleotide polymorphisms (SNPs) found in the candidate genes are measured using sanger sequencing at baseline in the intervention group only.
Overall trial start date
03/05/2014
Overall trial end date
22/05/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Blood pressure greater than 160 systolic or 90 diastolic
2.Currently on three medications including a diuretic
3. Attending the hypertension clinic at the study site
4. Aged 18 and over
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
120
Participant exclusion criteria
1. Renal failure
2. Congestive heart failure
3. Patients with a serious health condition that would limit life expectancy to less than one year
Recruitment start date
03/07/2014
Recruitment end date
03/07/2015
Locations
Countries of recruitment
Kenya, Nigeria, South Africa
Trial participating centre
Ladoke Akintola University of Technology Teaching Hospital
Cardiology Clinic
Department of Medicine
General area
Ogbomoso-Ilorin Road
Ogbomoso
202061
Nigeria
Trial participating centre
Groote Schuur Hospital
Hypertension Clinic
Cape Town
7925
South Africa
Trial participating centre
Nakuru County Referral Hospital
Medical Outpatient Department
Nakuru Town
20100
Kenya
Sponsor information
Organisation
Grand Challenges Canada
Sponsor details
Sandra Rotman Centre
MaRS Centre
South Tower
101 College Street
Suite 406
Toronto
M5G 1L7
Canada
+1 416 673 8122
winnie.luong@grandchallenges.ca
Sponsor type
Charity
Website
Funders
Funder type
Government
Funder name
Grand Challenges Canada
Alternative name(s)
Grands Défis Canada
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Canada
Results and Publications
Publication and dissemination plan
An abstract has been presented at a meeting in Maputo, Mozambique, April 18 - 19, 2016. Planned submission of a paper on the main results in June 2016, and a paper on the genetic sequencing results in July 2016
Intention to publish date
31/12/2016
Participant level data
Available on request
Basic results (scientific)
Publication list
2017 results in https://www.ncbi.nlm.nih.gov/pubmed/28472315