The coArtHA trial-identifying the most effective treatment strategies to control arterial hypertension in sub-Saharan Africa: study protocol for a randomized controlled trial

Abstract

Background: Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa.

Methods: In this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥ 18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90 mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤ 130/80 mmHg and ≤ 140/90 mmHg among those aged < 65 years and ≥ 65 years, respectively. Clinical manifestations of end-organ damage and cost-effectiveness at 6 months are secondary endpoints.

Discussion: This trial will help to identify the most effective and cost-effective treatment strategies for uncomplicated arterial hypertension among people of African descent living in rural sub-Saharan Africa and inform future clinical guidelines on antihypertensive management in the region.

Trial registration: Clinicaltrials.gov NCT04129840 . Registered on 17 October 2019 ( https://www.clinicaltrials.gov/ ).

Keywords: Antihypertensive therapy; Arterial hypertension; Blood pressure; Dual therapy; HIV; Randomized controlled trial; Sub-Saharan Africa; Tanzania and Lesotho; Triple therapy.

Fig. 1

Study interventions and drug dosing according to study arm. OD, once daily. ^$ Increases in dosages only if target BP is not reached (see above). * In case of orthostatic hypotension or adverse events, medication will be reduced to the prior step—or to half of the initial dosage. ** if regimen shows insufficient effect, individualized adaptation possible according the treating physician

Fig. 2

Study visit schedule. SV, screening visit; ER, enrolment; FUP, follow-up; EOS, end of study; ALT, alanine aminotransferase; Alb/Crea, albumin/creatinine; HIV, human immunodeficiency virus. *Day 0 (screening) and day 1 (enrolment) are the same day for participants not enrolled in the 24-h ambulatory BP study, £for all women of reproductive age (18–45 years), ** in 100 participants from Ifakara (nested study)