Identifying Most Effective Treatment Strategies to Control Arterial Hypertension in Sub-Saharan Africa

Study Overview
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Brief Summary
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This study is to compare the effectiveness of three different antihypertensive treatment strategies for reaching a target blood pressure (clinic BP) of </= 130/80 mmHg among patients <65years of age and </= 140/90 mmHg among patients >/=65years of Age in HIV-positive and HIV-negative patients with uncomplicated arterial hypertension in rural Tanzania and Lesotho.

Official Title
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Identifying Most Effective Treatment Strategies to Control Arterial Hypertension in Sub-Saharan Africa - A Randomized Controlled Trial

Conditions
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Arterial Hypertension

Intervention / Treatment
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* Other: dual combination
* Other: triple combination
* Other: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-positive and negative patients of African descent and black ethnicity with a documented uncomplicated, untreated arterial hypertension (blood pressure >/=140/90 mmHg) diagnosed at one of the 2 study sites Exclusion Criteria: Current hospitalization for any reason Not of African descent Refusal of an HIV-test or indeterminate HIV test result History of cardiovascular event in the last month (anginal pain, stroke, myocardial infarction or diagnosis by a doctor) Symptomatic arterial hypertension (blood pressure >/=180/110 mmHg plus headache or chest pain) or acute cardiovascular event acute disease, (e.g. fever >37.5°C or other signs of acute concomitant infection; Dyspnea/respiratory distress; Acute pain) Clinical signs of hypertension-mediated organ damage (heart failure, bilateral pitting edema, bilateral crackles or pleural effusion, distended jugular veins, ischemic heart disease (anginal pain on exertion), signs of current ischemic/hemorrhagic stroke (hemiparesis, loss of consciousness) Pregnancy (test required for females 18-45years of age) Non-consenting or inability to come for follow-up visits creatinine clearance </=30ml/min by Chronic Kidney Disease Epidemiology Formula (CK-EPI) estimation and measurement with a point-of care creatinine from capillary blood

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The intervention is a treatment algorithm (comparing two combination treatment strategies with the World Health Organization (WHO) standard and not an individual drug.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention 1: dual combination<br>dual combination of half-dose Calcium Channel Blocker (CCB) and Angiotensin II Receptor Blocker (ARB), dosage increases at 4 and 8 weeks if target blood pressure is not reached at the respective time point | Other: dual combination<br>* Participants will be started on a dual therapy with half dose of CCB and an ARB. If needed, a) the dose of the CCB will be increased at 4 weeks, and b) the dose of the ARB at 8 weeks, if blood pressure remains uncontrolled ((if target blood pressure is not achieved at this time point (target blood pressure defined as clinic BP </=130/80mmHg in patients <65years and </=140/90mmHg in patients >65years)<br>|
| Active Comparator: Intervention 2: triple combination<br>triple combination of quarter-dose of Calcium Channel Blocker (CCB), Thiazide diuretic (TZD) and Angiotensin II Receptor Blocker (ARB) with dosage increases of all drugs at 4 and 8 weeks, if target blood pressure is not reached at the respective time point | Other: triple combination<br>* Participants will be started with low dose (1/4) triple combination treatment with CCB, TZD and ARB. If uncontrolled after 4 weeks, dosages of all drugs will be doubled. If after 8 weeks still uncontrolled dosage will be increased to full dose of all three drugs ((if target blood pressure is not achieved at this time point (target blood pressure defined as clinic BP </=130/80mmHg in patients <65years and </=140/90mmHg in patients >65years)<br>|
| Placebo Comparator: Standard of care<br>start normal dose Calcium Channel Blocker (CCB), add Thiazide diuretic (TZD) after 4weeks and increase of TZD dosage after 8 weeks, if target blood pressure is not reached at the respective time point | Other: Standard of care<br>* Participants will be started on regular dose of CCB with a) addition of TZD at 4 weeks, if needed, b) increase of dose of TZD after 8 weeks, if needed (if target blood pressure is not achieved at this time point (target blood pressure defined as clinic BP </=130/80mmHg in patients <65years and </=140/90mmHg in patients >65years)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reaching a target blood pressure | Proportion of patients reaching a target blood pressure (clinic blood pressure) of </=130/80 mmHg in patients <65years of age and </=140/90 mmHg in patients >65years of age | at 12 weeks after enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reaching a target blood pressure | Proportion of patients reaching a target blood pressure (clinic blood pressure) of </=130/80mmHg in patients <65years of age and </=140/90mmHg in patients >65years of age | at 4, 8 and 24 weeks after enrolment | 
| Change in blood pressure (mmHg) | Change in blood pressure (change from enrolment) (mmHg) | at 4, 8, 12, 24 weeks after enrolment | 
| Proportion of patients with treatment adaptations made to the primary treatment | Proportion of patients with treatment adaptations made to the primary treatment (dose increases and/or drug additions) | within 12 weeks after enrolment | 
| Number of treatment adaptations per patient made to the primary treatment | Number of treatment adaptations per patient made to the primary treatment | within 12 weeks after enrolment | 
| Time until first target blood pressure of </=130/80 mmHg in patients <65years of age and </=140/90mmHg in patients >65years of age | Time until first target blood pressure of </=130/80 mmHg in patients <65years of age and </=140/90mmHg in patients >65years of age | within 24 weeks after enrolment | 
| Proportion of patients with major cardiovascular endpoints | Proportion of patients with major cardiovascular endpoints such as death, stroke, myocardial infarction, heart failure) | within 24 weeks after enrolment | 
| Proportion of patients with changes in surrogate markers for hypertension-mediated organ damage | Proportion of patients with changes in surrogate markers for hypertension-mediated organ damage (resolving, newly occurring or worsening) | within 24 weeks after enrolment | 
| Proportion of patients lost to follow up or stopped treatment | Proportion of patients lost to follow up or stopped treatment | within 24 weeks after enrolment | 
| Proportion of patients with at least one grade 3/4 adverse event | Proportion of patients with at least one grade 3/4 adverse event | within 24 weeks after enrolment | 
| Proportion of patients with at least one severe adverse event | Proportion of patients with at least one severe adverse event | within 24 weeks after enrolment | 
| Proportion of patients who were non-adherent to drugs | Proportion of patients who were non-adherent to drugs (<90% pill count or <90% of self-reported drug intake) | at 12 weeks after enrolment | 
| Reasons for non-adherence assessed by pill count (descriptive analysis) | Reasons for non-adherence assessed by pill count (descriptive analysis) | within 24 weeks after enrolment | 
| Cost-effectiveness of the 3 treatment algorithms | Cost-effectiveness of the 3 treatment algorithms | within 24 weeks after enrolment | 
| Proportion of patients with white coat hypertension, as determined by 24h ambulatory blood pressure measurement | Proportion of patients with white coat hypertension, as determined by 24h ambulatory blood pressure measurement | within 12 weeks after enrolment | 
| Proportion of patients with blood pressure control determined by 24h ambulatory blood pressure measurement (24h mean blood pressure <130/80mmHg irrespective of age) | Proportion of patients with blood pressure control determined by 24h ambulatory blood pressure measurement (24h mean blood pressure <130/80mmHg irrespective of age) | within 12 weeks after enrolment | 
| Reasons for non-adherence assessed by self-report (descriptive analysis) | Reasons for non-adherence assessed by self-report (descriptive analysis) | within 24 weeks after enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antihypertensive treatment