Because ivermectin is being used to treat COVID-19 with insufficient evidence, the investigator conducted a randomized clinical trial to investigate the efficacy and safety of ivermectin in comparison to hydroxychloroquine and placebo in severe COVID-19 patients. The study was conducted in Shebin-Elkom teaching hospital and recruited patients from December 6, 2020, to January 31, 2021.

This study is an adaptive, randomized, double-blinded, controlled trial to evaluate the safety and efficacy of therapeutic agents in hospitalized adult patients diagnosed with COVID-19. The study is a single-center trial that will be conducted in Shebin Elkom teaching hospital. The study will be a series of 3-arm comparisons between two different investigational therapeutic agents (Ivermectin and Hydroxychloroquine) and a placebo. There will be interim monitoring to allow early stopping for futility, efficacy, or safety. Because of the possibility that background standards of supportive care may evolve/improve over time as more is learned about the successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized participants. An independent data and safety monitoring board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms.

Inclusion Criteria:

1. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
2. Understands and agrees to comply with planned study procedures.
3. Agrees to the collection of OP swabs and venous blood per protocol.
4. Male or non-pregnant female adult ≥18 years of age at time of enrollment.
5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other
6. Severe cases according to WHO definition.

Exclusion Criteria:

1. ALT/AST > 5 times the upper limit of normal.
2. Mortality within 12 hours of admission.
3. Pregnancy.
4. Anticipated transfer to another hospital within 24 hours.
5. Allergy to any study medication commercial or public health assay in any specimen prior to randomization.
6. Mechanically ventilated on admission

Unlabelled tablets were prepared for each patient in a special envelope in a time-based manner in the central pharmacy