Protocol of Pakistan randomized and observational trial to evaluate coronavirus treatment among newly diagnosed patients with COVID-19: Azithromycin, Oseltamivir, and Hydroxychloquine

Abstract

Background & Objective: This study aimed to assess the clinical effectiveness of Hydroxychloroquine Sulfate (200 mg orally 8 hourlies thrice a day for 5 days), oseltamivir (75 mg orally twice a day for 5 days), and Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in seven groups). Methods & Analysis: An adaptive design is deployed, set within a comprehensive cohort study, to permit flexibility in fast-changing clinical and public health scenario. Primary outcomes include turning the test negative for coronavirus nucliec acid and in bringing about clinical improvement on day 7 of follow-up on a seven-point ordinal scale. The randomized study will recruit participants of either gender above 18 years of age who will test positive for SARS-CoV-2 on Quantitative Reverse Transcription Polymerase Chain Reaction (PCR). Pregnant or lactating females, and those with severe respiratory distress, or with serious comorbidities will be excluded. Randomization will be done maintaining concealment of allocation sequence using a computer-generated random number list. The sample size will be subjected to periodic reviews by National Data Safety and Monitoring Board. Ethics and Dissemination: The trial is approved by the National Bioethics Committee (No.4-87/NBC-471-COVID-19-05/20/) and institutional Ethical Review Committee. This clinical trial conducted under Good Clinical Practice is expected to inform patients clinical guidelines for the use of these drugs in newly diagnosed with SARS-CoV-2. Trial Registration: The trial was prospectively registered on April 08, 2020 at clinicaltrials.gov with ID: NCT04338698.