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.