Abstract: Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial Pauline Byakika-Kibwika (  pbyakika@gmail.com ) Makerere University College of Health Sciences Christine Sekaggya-Wiltshire Mulago National Referral Hospital Jerome Roy Semakula Makerere University College of Health Sciences Jane Nakibuuka Mulago National Referral Hospital Joseph Musaazi Makerere University College of Health Sciences James Kayima Makerere University College of Health Sciences Cornelius Sendagire Makerere University College of Health Sciences David Meya Makerere University College of Health Sciences Bruce Kirenga Makerere University College of Health Sciences Sarah Nanzigu Makerere University College of Health Sciences Arthur Kwizera Makerere University College of Health Sciences Fred Nakwagala Mulago National Referral Hospital Ivan Kisuule Mulago National Referral Hospital Misaki Wayengera Makerere University College of Health Sciences Henry G Mwebesa Ministry of Health Page 1/23 Moses Kamya Makerere University College of Health Sciences William Bazeyo Makerere University College of Health Sciences Research Article Keywords: COVID-19, Hydroxychloroquine, outcomes, treatment, safety, efficacy. Posted Date: June 4th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-506195/v1 License:   This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/23 Abstract Background Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design We conducted a randomized open label Phase II clinical trial from October -December 2020. Methods Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400mg twice a day for the first day followed by 200mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. Results Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3-4) vs 4(2-4): p=0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. Conclusion Our results show that HCQ..