The number of patients with COVID-19 in Singapore was coming down for the community and the concerns about the potential side effects particularly when the baseline ECG and serum electrolytes was not proposed.

The Coronavirus Disease 2019 (COVID-19) pandemic has placed tremendous stress on the global economy since its outbreak in December 2019. Currently, with nearly 1.3 million confirmed cases, there is still no effective way to contain the disease. The transmission of COVID-19 occurs via direct (prolonged close interaction, within 2 meters for more than 30 minutes) and indirect (fomites) contacts. Locally, the risk of COVID-19 infection in household contacts of confirmed cases is about 4%. These at-risk individuals are identified through contact tracing and infectious may be preventable using post-exposure-prophylaxis (PEP). However, there has yet to be a single effective, safe, and affordable pharmacological agent with such capabilities. Hydroxychloroquine (HCQ) is a cheap anti-malarial and immunomodulatory agent which may potentially be used as PEP against COVID-19. HCQ is capable of blocking the invasion and intracellular replication of the virus. Existing studies have reported efficacy of HCQ in treating COVID-19, with reduced time to clinical recovery and few reports of patients suffering from significant side effects. However, existing studies are largely limited by their small sample sizes. Furthermore, there has yet to be a published trial on HCQ's role in PEP. This cluster randomized trial will evaluate the safety and efficacy of oral HCQ PEP, taken over for 5 days, in reducing the number of infected household contacts of confirmed COVID-19 patients under home quarantine. Comparison will be made between HCQ PEP (treatment group) and no treatment (control group). Subjects will be followed up over a course of 28 days, with daily symptom monitoring conducted over phone calls. Positive outcomes from this study will provide a means for us to battle the COVID-19 pandemic.

Inclusion criteria:

1. Aged 18 to 80 years.
2. History of close contact or exposure to positive COVID-19 cases in the same household.
3. Absence of symptoms resembling COVID-19 (e.g., fever and acute respiratory or gastrointestinal symptoms) for two weeks prior to enrolment for the study.
4. Able to give informed consent or in case of <21 and>/=18 years old subject, parents able to give consent for those individuals. In the event the household is unable to read or sign/date the ICF, an impartial witness to be present to ascertain the information, comprehension and voluntariness. The impartial witness must be able to read the informed consent form (ICF).
5. Able to comply with study procedures and follow-up
6. Singapore citizen, permanent resident or long-term pass-holder.

Exclusion Criteria:

1. Person diagnosed with COVID-19 infection.
2. Pregnant at the time of screening or breastfeeding.
3. Known allergy or hypersensitivity to HCQ or other aminoquinoline compounds.
4. Already on HCQ for different indications (e.g., rheumatological diseases, malaria prophylaxis)
5. Diagnosis of other systemic viral or bacterial infection.
6. Use of systemic immunosuppressant agents within 90 days of enrollment (e.g., corticosteroids and immunomodulatory therapy)
7. History of immunocompromised state.
8. History of psychiatric illness.
9. History of psoriasis or porphyria.
10. History of cardiac disease.
11. Other major comorbidities that contraindicate the use of HCQ: i. Hematologic malignancy, ii. Stage 4-5 chronic kidney disease or end-stage renal failure, iii. history of ventricular arrhythmias, iv. current use of drugs that prolong the QT interval
12. History of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
13. Bradycardia <50beats/min.
14. Uncorrected hypokalemia
15. Uncorrected hypomagnesemia.
16. Unwillingness to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) while on study and for at least 30 days after last dose.