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

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

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.

Study Overview

• Status: Completed
• Conditions: Arterial Hypertension
• Intervention / Treatment: Other: dual combination; Other: triple combination; Other: Standard of care

• Study Type: Interventional
• Enrollment (Actual): 1268
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Lesotho
  • Mokhotlong, Lesotho
    • SolidarMed Lesotho, Mokhotlong Government Hospital
• Switzerland
  • Basel, Switzerland, 4031
    • Division of Infectious Diseases & Hospital Epidemiology; University Hospital Basel
• Tanzania
  • Morogoro
    • Ifakara, Morogoro, Tanzania
      • St. Francis Referral Hospital/ Ifakara Health Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention 1: dual combination; 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; 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 65years)
Active Comparator: Intervention 2: triple combination; 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; 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 65years)
Placebo Comparator: Standard of care; 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; 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 65years)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Swiss National Fund for Scientific Research
• Investigators: Principal Investigator: Maja Weisser Rohacek, PD Dr., Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel

Publications and helpful links

General Publications

• Mapesi H, Gupta R, Wilson HI, Lukau B, Amstutz A, Lyimo A, Muhairwe J, Senkoro E, Byakuzana T, Mphunyane M, Bresser M, Glass TR, Lambiris M, Fink G, Gingo W, Battegay M, Paris DH, Rohacek M, Vanobberghen F, Labhardt ND, Burkard T, Weisser M. The coArtHA trial-identifying the most effective treatment strategies to control arterial hypertension in sub-Saharan Africa: study protocol for a randomized controlled trial. Trials. 2021 Jan 21;22(1):77. doi: 10.1186/s13063-021-05023-z.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2020
• Primary Completion (Actual): September 22, 2022
• Study Completion (Actual): September 22, 2022

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: antihypertensive treatment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 2019-00817; qu19Weisser

Drug and device information, study documents

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