Doxycycline vs Hydroxychloroquine + Azithromycin in the Management of COVID-19 Patients: An Open-Label Randomized Clinical Trial in Sub-Saharan Africa (DOXYCOV)

Objective We aimed to compare the safety and efficacy of a doxycycline-based regimen against Cameroon National Standard Guidelines (hydroxychloroquine plus azithromycin) for the treatment of mild symptomatic COVID-19. Methods We conducted an open-label, randomized, non-inferiority trial in Cameroon comparing doxycycline 100 mg, twice daily for seven days versus hydroxychloroquine 400 mg daily for five days and azithromycin 500 mg at day 1 and 250 mg from day 2 through 5 in mild COVID-19 patients. Clinical recovery, biological parameters, and adverse events were assessed. The primary outcome was the proportion of clinical recovery on days 3, 10, and 30. Non-inferiority was determined by the clinical recovery rate between protocols with a 20-percentage points margin. Results One hundred and ninety-four participants underwent randomization and were treated either with doxycycline (n = 97) or hydroxychloroquine-azithromycin (n = 97). On day 3, 74/92 (80.4%) participants on doxycycline versus 77/95 (81.1%) on hydroxychloroquine-azithromycin-based protocols were asymptomatic (p = 0.91). On day 10, 88/92 (95.7%) participants on doxycycline versus 93/95 (97.9%) on hydroxychloroquine-azithromycin were asymptomatic (p = 0.44). On day 30, all participants were asymptomatic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) polymerase chain reaction (PCR) test was negative on day 10 in 60/92 (65.2%) participants who were assigned to doxycycline and in 63/95 (66.3%) participants who were assigned to hydroxychloroquine-azithromycin. None of the participants were admitted for worsening of the disease after treatment initiation. Conclusion Doxycycline 100 mg twice daily for seven days proved to be safe and non-inferior in terms of efficacy when compared to hydroxychloroquine-azithromycin for preventing clinical worsening of mild symptomatic or asymptomatic COVID-19 and achieving virological suppression.