High-Dose Hydroxychloroquine for Ambulatory Patients with
COVID-19: Our Center’s Experience
With this pharmacologic rationale, our group designed a single arm and
single-center study evaluating the tolerability of high-dose
hydroxychloroquine therapy, 600 mg twice daily for five days, in
outpatient adult participants with mild COVID-19 with risks factors for
clinical decompensation (NCT04351620). Our secondary objectives were to
evaluate whether high-dose hydroxychloroquine lead to symptom relief,
defervescence and maintenance of ambulatory status. Patients were
eligible for inclusion in our trial if they were SARS-CoV-2 PCR
positive, had one fever greater than 100.4 F within 48 hours of
enrollment, manifested symptoms consistent with the disease, and had one
additional risk factor associated with hospitalization. These risk
factors included age > 55, pre-existing pulmonary,
cardiovascular, kidney disease, diabetes, hypertension, or one fever
every 24 hours for > 72h. Patients with history of
cardiovascular disease were required to have had an electrocardiogram
within the past thirty days showing a normal QT interval (QT <
500 ms). Patients with more advanced kidney disease, history of retinal
disease, history of QT prolongation or other arrhythmias, use of QT
prolonging medications and pregnant or lactating women were excluded
from the study.
We designed our trial to enroll a high-risk ambulatory population with
mild illness whom stood to benefit more from early intervention with
hydroxychloroquine. Mild illness is defined by symptoms of upper
respiratory tract infection, including fever, dry cough, sore throat,
nasal congestion, anosmia, ageusia, fatigue, myalgia, and headaches
without pneumonia or with mild pneumonia.[27] Mild illness can
progress to severe illness characterized by respiratory failure with or
without shock and multi-organ failure. Although risk factors for
hospitalization due to COVID-19 had not been well-defined, several
studies reported similar epidemiological risk factors associated with
severe disease and in-hospital mortality, including older age, and
chronic medical conditions such as hypertension and diabetes.[28,
29] Screening, informed consent and entry into the trial was completed
remotely allowing for patients to remain quarantined. Upon notification
of a positive SARS-CoV-2 test result by the University of Chicago
Infection Control, patients were asked permission to be contacted by our
study team. Once contacted, formal screening and informed consent were
completed over the phone by study investigators. No clinical laboratory
assessments were required upon screening, during, or at end of the
study. If enrolled, hydroxychloroquine was delivered to their home
address by the University of Chicago Specialty Pharmacy within 24 hours
of enrollment. While participating in the study, patients were asked to
check and log their body temperature twice a day and record antipyretic
use. A standardized symptom assessment was performed daily while the
participant was taking hydroxychloroquine, 5 days, and at a
pre-specified Day 14 follow up at which point their participation in the
study was complete. The study was approved by the University of Chicago
Institutional Review Boards.
Over a six-week period, 59 patients met eligibility criteria out of 314
patients contacted (18.7%). Out of these 59 potentially eligible
patients, 44 (74.5%) patients declined to be screened further due to
concerns about the risks and unproven efficacy of the medication, often
referencing media accounts and touting of the drug by President of the
United States. Fifteen completed the “Pre-Treatment Assessment” and 9
signed the Telephone Consent, with 7 continuing on to receive the
medication. Two patients discontinued the treatment because of side
effects, one of whom did not follow-up and the other was unable to
tolerate either the original dose or the dose reduction protocol because
of headaches. While we were unable to confirm with certainty that this
was a medication effect, it was deemed prudent to end their enrollment.
The remaining patients were able to complete their courses, hence
meeting the primary outcome of tolerability. Two of the patients
reported rapid improvement in fever and myalgia within 24 hours of
starting the treatment. One patient continued to have fevers throughout
the course and was admitted to hospital for pneumonitis. Incidentally,
EKG obtained on admission demonstrated a normal QTc interval. Another
patient had fevers through the entire study period. Hence with the small
sample size, no conclusions could be drawn and the study was terminated
early due to recruitment difficulties, with many patients contacted by
the team citing negative media reports on the drug as the reason behind
their disinterest.