The study proposes to conduct an open-label Phase II trial to evaluate the feasibility, safety and early efficacy of hydroxychloroquine (HCQ) administration in reduction of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and development of Corona Virus Disease 2019 (COVID-19) in high-risk, healthy acute care provider participants exposed, directly or indirectly, to COVID-19 patients. There is a more than 50 years track record of safety of HCQ for treatment and prevention of various disease states. Early data on use of HCQ for COVID treatment suggests anti-viral activity and immunomodulatory properties for reducing inflammation associated with COVID-19.
Given the lack of data regarding use of HCQ for COVID-19 prevention in healthy participants
in midst of pandemic crisis, this study proposes an expedited feasibility study focusing on
safety and early efficacy.
Prior to HCQ administration, baseline SARS-CoV-2 and other baseline biomarker testing will be
conducted. During the 4-week study period, participants will be monitored for drug related
adverse events and assessed for development of COVID. SARS-CoV-2 assay and biomarker testing
will be repeated at the end of four-week study. Safety outcomes will be assessed by the
number of adverse events (AEs) and their severity; and early efficacy as the number of
participants who tested positive at the end of the 4-week period comparing to data collected
by occupational Health regarding the total number of high-risk healthcare workers that were
tested positive during the same period and historical controls from known high risk infection
rates. An exploratory analysis of inflammatory regulation and immunomodulatory markers by HCQ
and its effect on possible disease modification based on previously studied
pathophysiological mechanism of COVID-19.
The broader aim of this study is to set a precedent to facilitate a large-scale emergent
public health intervention. Purpose would be to mitigate, or abort further transmission of
COVID-19. Given that COVID-19 transmission has occurred prior to initiation of this study,
the rationale for this intervention is based on prior epidemiological evidence.
Post-infectious or vaccination-induced immunity in at least 30% of population at-risk has
been shown to mitigate or abort propagation of a local epidemics and global pandemic. This
would help flatten the curve of the disease progression, until such time that a vaccine may
become available. Data from this study will be used to design and implement a
population-based phase IIb/III randomized clinical trial.
Drug: Hydroxychloroquine Sulfate (HCQ)
Open-label, consecutive at-risk subjects allocation with chemoprophylaxis with HCQ.
Inclusion Criteria:
- Volunteers ages 18 to 99 years,
- Able to sign own informed consent form,
- Considered high-risk healthcare care providers in a hospital setting with active
exposure to COVID-19 infection.
High-risk healthcare providers are defined as those actively working during the study
duration in the Emergency Department and in the Intensive Care Setting, for the purpose of
this study.
Exclusion Criteria:
- Inability to tolerate an oral medication or known allergy to chloroquine or
hydroxychloroquine
- Pregnancy or breast-feeding
- Immunocompromised status, hepatic failure, electrolytic imbalance
- Creatinine clearance (CCL) <30 mL/min
- Prolonged QT interval (QTc > 450ms for males and QTc > 470 for females)
- Confirmed COVID-19 infection on baseline testing
- Has another known contraindication to treatment with the study drug, including
retinopathy.
Hackensack Meridian Health - JFK Medical Center
Edison, New Jersey, United States
Jawad Kirmani, MD, Principal Investigator
Hackensack Meridian Health Corporation