Low-Dose Triple-Pill vs Standard-Care Protocols for Hypertension Treatment in Nigeria: A Randomized Clinical Trial

Abstract

Importance: With the high burden of hypertension in sub-Saharan Africa, there is a need for effective, safe and scalable treatment strategies.

Objective: To compare, among Black African adults, the effectiveness and safety of a novel low-dose triple-pill protocol compared with a standard-care protocol for blood pressure lowering.

Design and setting: Randomized, parallel-group, open-label, multicenter trial conducted in public hospital-based family medicine clinics in Nigeria.

Participants: Black African adults with uncontrolled hypertension (≥140/90 mm Hg) who were untreated or receiving a single blood pressure-lowering drug.

Interventions: Participants were randomly allocated to low-dose triple-pill or standard-care protocols. The triple-pill protocol involved a novel combination of telmisartan, amlodipine, and indapamide in triple one-quarter, one-half, and standard doses (ie, 10/1.25/0.625 mg, 20/2.5/1.25 mg, and 40/5/2.5 mg), with accelerated up-titration. The standard-care protocol was the Nigeria hypertension treatment protocol starting with amlodipine (5 mg).

Main outcomes and measures: The primary effectiveness outcome was the reduction in home mean systolic blood pressure, and the primary safety outcome was discontinuation of trial treatment due to adverse events, both from randomization to month 6.

Results: The first participant was randomized on July 19, 2022, and the last follow-up visit was on July 18, 2024. Among 300 randomized participants (54% female; mean age, 52 years; baseline mean home blood pressure, 151/97 mm Hg; and clinic blood pressure, 156/97 mm Hg), 273 (91%) completed the trial. At month 6, mean home systolic blood pressure was on average 31 mm Hg (95% CI, 28 to 33 mm Hg) lower in the triple-pill protocol group and 26 mm Hg (95% CI, 22 to 28 mm Hg) lower in the standard-care protocol group (adjusted difference, -5.8 mm Hg [95% CI, -8.0 to -3.6]; P < .001]). At month 6, clinic blood pressure control (<140/90 mm Hg) was 82% vs 72% (risk difference, 10% [95% CI, -2% to 20%]) and home blood pressure control (<130/80 mm Hg) was 62% vs 28% (risk difference, 33% [95% CI, 22% to 44%]) in the triple-pill compared with the standard-care protocol group; these were 2 of 21 prespecified secondary effectiveness end points. No participants discontinued trial treatment due to adverse events.

Conclusions and relevance: Among Black African adults with uncontrolled hypertension, a low-dose triple-pill protocol achieved better blood pressure lowering and control with good tolerability compared with the standard-care protocol.

Trial registration: Pan African Clinical Trials Registry Identifier: PACTR202107579572114.

Figure 1.. Screening, Randomization, and Flow of Participants

Figure 2.. Home and Clinic Mean Blood Pressure Over Time, by Group

Crude mean blood pressure and standard deviation at each visit are reported. Estimates for each participant at each visit are calculated from all available home blood pressure measurements since previous clinic visit. The number of participants with available blood pressure data at each visit is reported at the bottom of the figure. Note, numbers are only provided for times when clinic visits were performed, since clinic blood pressure was measured then and home blood pressure measurement frequency was increased before these visits. These were purposefully differential; for example, the triple-pill protocol group had an extra visit in week 2 but no visits in months 4 and 5.

Figure 3.. Blood Pressure–Lowering Drug Regimens at Each Follow-Up Visit

Regimen refers to blood pressure–lowering drugs patients were taking. Data are percentage of participants receiving blood pressure–lowering drugs coming into clinic visit, with percent calculated using denominator of number attending the visit (N) with data available. A5 indicates amlodipine (5 mg); HCTZ, hydrochlorothiazide; T40, telmisartan (40 mg).