Background/Purpose: Coronavirus disease 2019 (COVID-19) was first recognized in December 2019 and quickly became a global pandemic within months. Amidst a myriad of uncertainties, early data from in-vitro analysis and a small-population retrospective study demonstrated promise for hydroxychloroquine (HCQ), a small molecule oral drug prevalently used for rheumatic diseases and previously in malarial therapy. The news of HCQ and its use in COVID-19 disseminated through social media channels and rose to international attention before proper conduct of large population, prospective clinical studies. It is within this capricious global environment that we discuss the unique pharmacokinetic (PK) reasoning for use of high dose HCQ in mild COVID-19 and subsequent proceedings of our phase I clinical trial and associated challenges.

Methods: We conducted a single-center, single-arm tolerability study for ambulatory patients with mild COVID-19 and risk factors for progression to moderate or severe disease. Physiologically based PK modeling suggests HCQ loading doses between 400 mg BID and 600 mg BID are effective in achieving desired lung tissue concentration, potentially enabling a faster clinical effect. Enrollment and consent were obtained remotely through a telephonic interaction between a physician and participant while the participant utilized the REDCap electronic consent platform. Participants took HCQ 600 mg twice daily for 5 days. Changes in symptoms and side effects were assessed via daily telephone questionnaire, with tolerability of HCQ at day 14 as the primary endpoint. Tolerability of the regimen was deemed acceptable if 80% of patients completed the protocol. Figure 1 shows the timeline of media releases with HCQ study recruitment.

Results: Ultimately, only 7 patients were enrolled in the study and 6 completed the 5 day course. Five patients (71%) tolerated the course without any side effects. One patient developed headaches, while another had nausea, vomiting, and diarrhea, was lost to follow up, and later hospitalized. After numerous reports in the media of potential severe side effects and ineffectiveness of HCQ for COVID-19 treatment, public opinion of HCQ shifted and potential participants became unwilling to be enrolled in the study, leading to its termination on 5/29/2020.

Conclusion: While a limited number of participants enrolled, no serious side effects were noted with use of high dose HCQ in mild COVID-19. We demonstrate that a large cohort prospective trial properly assessing HCQ in mild COVID-19 has many challenges in the current atmosphere, but given the tolerability of high doses HCQ, future research should give consideration of studying the potential benefit of this dose in rheumatic disease. (clinicaltrials.gov, NCT04351620)

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/phase-i-trial-of-high-dose-hydroxychloroquine-for-the-treatment-of-ambulatory-patients-with-mild-covid-19-a-study-in-the-effects-of-shifting-public-opinion-on-patient-enrollment/