Safety And Efficacy Of Hydroxychloroquine For At Risk Population (SHARP) Against COVID-19 (SHARP COVID-19)

Safety And Efficacy Of Hydroxychloroquine For At Risk Population (SHARP) Against COVID-19- A Cluster Randomized Controlled Trial (SHARP COVID-19 RCT)

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.

Study Overview

• Status: Withdrawn
• Conditions: Coronavirus Infection; Hydroxychloroquine Adverse Reaction
• Intervention / Treatment: Drug: Hydroxychloroquine Sulfate 200 milligram (mg) Tab

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Treatment arm will be given Hydroxychloroquine sulfate. Dose: 800 milligrams (mg) (4 pills of 200mg) in two divided doses on day 1 followed by 400mg (2 pills of 200mg) in two divided doses on day 2, 3,4, 5. Mode of administration: Oral pills of 200mg of HCQ; Supply: The total supply of all the pills (12 pills of 200mg per subject in the study group) will be given to the recruited subject from day 1.	Drug: Hydroxychloroquine Sulfate 200 milligram (mg) Tab; Oral tablet of Hydroxychloroquine sulfate
Other: Standard Preventive Measures; No intervention. Standard recommended preventive measures by the ministry of health.	Drug: Hydroxychloroquine Sulfate 200 milligram (mg) Tab; Oral tablet of Hydroxychloroquine sulfate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
positive serology or reverse transcriptase (RT-PCR) for COVID-19 up until day 28.	COVID-19 infection	Until day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive serology at day 28.	Serology	28 days
Symptoms of COVID-19.	COVID-19	Until day 28

Collaborators and Investigators

• Sponsor: Tan Tock Seng Hospital
• Collaborators: Netherlands: Ministry of Health, Welfare and Sports; Duke-NUS Graduate Medical School; Singapore Clinical Research Institute; Singapore Eye Research Institute; Saw Swee Hock School of Public Health; National Center for Infectious Diseases
• Investigators: Principal Investigator: Rupesh Agrawal, MD, Tan Tock Seng Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; Hydroxychloroquine; Singapore; Post Exposure Prophylaxis (PEP)
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 2020/00402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No