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

Herry Mapesi, Ravi Gupta, Herieth Ismael Wilson, Blaise Lukau, Alain Amstutz, Aza Lyimo, Josephine Muhairwe, Elizabeth Senkoro, Theonestina Byakuzana, Madavida Mphunyane, Moniek Bresser, Tracy Renée Glass, Mark Lambiris, Günther Fink, Winfrid Gingo, Manuel Battegay, Daniel Henry Paris, Martin Rohacek, Fiona Vanobberghen, Niklaus Daniel Labhardt, Thilo Burkard, Maja Weisser, Herry Mapesi, Ravi Gupta, Herieth Ismael Wilson, Blaise Lukau, Alain Amstutz, Aza Lyimo, Josephine Muhairwe, Elizabeth Senkoro, Theonestina Byakuzana, Madavida Mphunyane, Moniek Bresser, Tracy Renée Glass, Mark Lambiris, Günther Fink, Winfrid Gingo, Manuel Battegay, Daniel Henry Paris, Martin Rohacek, Fiona Vanobberghen, Niklaus Daniel Labhardt, Thilo Burkard, Maja Weisser

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.

Conflict of interest statement

All authors declare that they have no competing interests.

Figures

Fig. 1
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
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)

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