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Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical ....

Updated: Sep 19, 2021

Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical worsening and hospitalization in mild COVID-19 patients: An open-label randomized clinical trial (DOXYCOV)

Abstract Objective We aimed to compare the safety and efficacy of a doxycycline-based regimen against the national standard guidelines (Hydroxychloroquine plus Azithromycin) for the treatment of mild symptomatic COVID-19.

Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical worsening and hospitalization in mild COVID-19 patients: An open label randomized clinical trial (DOXYCOV)

Methods We conducted an open-label, randomized, non-inferiority trial, in Cameroon comparing Doxycycline 100mg, twice daily for 7 days versus Hydroxychloroquine, 400 mg daily for 5 days and Azithromycin 500mg at day 1 and 250mg from day 2 through 5, in mild COVID-19 patients. Clinical improvement, biological parameters, and adverse events were assessed. The primary outcome was the proportion of clinical cures at days 3, 10, and 30. Non-inferiority was determined by the clinical cure rate between protocols with a 20 percentage points margin. Results 194 participants underwent randomization and were treated 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. SARS-CoV2 PCR was negative at Day 10 in 60/92 (65.2%) participants allocated to Doxycycline and 63/95 (66.3%) participants allocated to Hydroxychloroquine-Azithromycin. None of the participants were admitted for worsening of the disease after treatment initiation. Conclusion Doxycycline 100 mg twice daily for 7 days is as effective and safe as Hydroxychloroquine-Azithromycin, for preventing clinical worsening of mild symptomatic or asymptomatic COVID-19 and achieving virological suppression. Strengths and Limitations

  • ➢ This study is one of the first randomized trials, assessing the efficacy and tolerance of Doxycycline to treat COVID-19

  • ➢ It is one of the first to evaluate disease progression and needs to hospitalization in mild or asymptomatic COVID-19

  • ➢ Patients will not receive identical treatments

  • Doxycycline has advantages in terms of availability, safety, and cost compared to Hydroxychloroquine and Azithromycin

  • ➢ Though this study has encounter 7 lost to follow-up, this does not have a major influence on our results

  • ➢ These data will assist clinicians in their daily practice, and provide a new tool for the fight against COVID-19

Competing Interest Statement

The authors have declared no competing interests.

Clinical Trial


Funding Statement

The study was partially sponsored by a special grant from the French Embassy in Cameroon. The study benefited from material support from the RSD institute Yaounde Cameroon and Yaounde Central Hospital.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.


The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study received ethical clearance from the Cameroon National Ethics Committee (2020/07/1585/L/CNERSH/SP).

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.


I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).


I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Credited to Medrxiv


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