Hydroxychloroquine (HCQ) as Post Exposure Prophylaxis (PEP) for Prevention of COVID-19 (PEP-CQ)

Efficacy of Hydroxychloroquine (HCQ) as Post Exposure Prophylaxis (PEP) for Prevention of COVID-19 in Asymptomatic Individual at Risk for SARS-CoV-2 Infection-A Randomized Control Clinical Trial

COVID-19 affected more than 9 million of people with more than 130 thousand death in India. If adequate preventive and therapeutic measures are not taken, India has very high risk of affecting million of more people with high mortality because of the large population along with very high population density. At present there are no definitive therapeutic drugs or vaccine available for the treatment and prevention of SARS-CoV-2 infection. Symptomatic and supportive care are being given to COVID-19 cases along with isolation and quarantine measure are being taken for the suspected individual at risk for COVID-19 to limit the spread of the SARS-CoV-2 infection . Among the all the drugs being used for the treatment of COVID-19, hydroxychloroquine (HCQ), has given some rays of hope to battle against this deadly pandemic. HCQ has some anti viral effect against SARS-CoV in vitro. HCQ is quite safe and being used in rheumatology patients for lifelong without much side effect, so it allow for higher dose without any significant side effects and drug-drug interaction. Recently published clinical trial suggested HCQ can be used for the therapeutic purpose of the SARS-CoV-2 infection and many governments have endorsed that due to lack of any other better alternative drugs. Indian council of medical research (ICMR) has advised for HCQ prophylaxis for the people who are at risk for developing SARS-CoV-2 infection, all asymptomatic health care workers involved in taking care of suspected or confirmed COVID-19 cases and all asymptomatic household contacts of laboratory confirmed COVID-19 cases. With this encouragement an open level clinical trial was conducted on HCQ as post exposure prophylaxis (PEP) for the prevention of COVID-19 in asymptomatic high risk house hold contact of the laboratory confirmed COVID-19 cases. The result was very promising showing absolute risk reduction of around 9% in participant who received PEP with HCQ as compared to the control group and there was no serious adverse event. But there is still conflicting scientific data to prove or disprove the efficacy of HCQ for the treatment and prophylaxis for SARS-CoV-2 infection. Being a tertiary care center PGIMER is catering many states which include Punjab, hariyana, himachal Pradesh, Uttara khand, Uttar Pradesh. This put the institute to handle highest burden of suspected cases of SARS-CoV-2 in northern India. So, this double blind clinical trial has been planned to evaluate the efficacy of HCQ as PEP for the prevention of COVID-19 in asymptomatic individuals who are at risk for SARS-CoV-2 infection.

The asymptomatic individual with direct contact with laboratory confirmed COVID-19 cases will be randomized into one PEP group and one control/placebo group as per inclusion and exclusion criteria. Individual who will not give consent for HCQ prophylaxis and those with contraindication for HCQ therapy like, hypersensitivity to HCQ or 4-aminoquinolone derivatives, patients with known retionopathy, cardiac arrhythmia, G6PD deficiency, psoriasis and pregnancy will be excluded from the study. All symptomatic individual and all health care workers related to suspected or proven COVID-19 and who received CoVID-19 vaccine will be excluded from the study. The PEP group will receive tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks (total cumulative dose of 2000 mg). The control group will receive placebo instead of HCQ. Both the groups will receive standard care of therapy in the form of home quarantine for 2 weeks along with social distancing and personal hygiene. The participants will be followed up for 4 weeks telephonically or physically as and when required and will be enquired regarding development of any COVID-19 symptoms like fever, cough, sore throat, shortness of breath, diarrhoea, myalgia. During follow up nasopharyngeal swab of the participants will be taken for processing reverse transcription polymerase chain reaction (RTPCR) for the detection of SARS-CoV-2 RNA to confirm the CoVID-19. Samples for RTPCR will be taken when any asymptomatic participants becomes symptomatic and by the 5-14 days of contact in asymptomatic participants through in-hospital visit at the institute's COVID-19 screening clinic.

Study Overview

• Status: Recruiting
• Conditions: Covid19; COVID-19 Prevention
• Intervention / Treatment: Drug: Hydroxychloroquine (HCQ); Other: Standard care; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Deba Prasad dhibar, MD; Phone Number: +911722756670; Email: dhibar.dp@pgimer.edu.in

Study Locations

• India
  • Chandigarh, India, 160012
    • Recruiting
    • Post Graduate Institute of Medical education and Research
    • Contact: Deba Prasad dhibar, MD; Phone Number: +911722756670; Email: dhibar.dp@pgimer.edu.in

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Gender: Male/Female
2. Age of ≥18 years
3. Asymptomatic individual with direct contact with laboratory confirmed COVID-19 cases

Exclusion Criteria:

1. Symptomatic individual 2. Health care worker 3. Individual who will not give consent for HCQ prophylaxis 4. Contraindication for HCQ therapy 5. Pregnancy 6. Individual who received COVID-19 vaccine

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PEP group; Tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks (total 5 tablets, cumulative dose of 2000 mg)	Drug: Hydroxychloroquine (HCQ); Tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks (total 5 tablets, cumulative dose of 2000 mg ); Other: Standard care; Standard therapy in the form of home quarantine for 2 weeks along with social distancing and personal hygiene
Placebo Comparator: Control group; Placebo one tablet 12 hourly on day one followed by one tablet once weekly for 3 weeks (total 5 tablets)	Other: Standard care; Standard therapy in the form of home quarantine for 2 weeks along with social distancing and personal hygiene; Other: Placebo; Tablet placebo one tablet 12 hourly on day one followed by one tablet once weekly for 3 weeks (total 5 tablets)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of COVID-19	Both the definite and probable COVID-19 cases together are defined as COVID-19 case	4 weeks
Definite COVID-19	Participant with RTPCR positive for SARS-CoV-2 and with or without symptoms will be defined as definite COVID-19 case	4 weeks
Probable COVID-19	The participant with new onset symptoms, but RTPCR negative for SARS-CoV-2 or cannot be performed for any reason will be defined as probable COVID-19 case.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New onset symptoms of COVID-19	Incidence of new onset symptoms of COVID-19 in asymptomatic participants	4 weeks
Compliance	Percentage of participants will be completing the advised therapy	4 weeks
Adverse drug reaction (ADR)	Incidence of adverse drug reaction among the participants	4 weeks

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Covid19, Hydroxychloroquine (HCQ)
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: INT/IEC/2021/SPL456

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: All data requests should be submitted to the PI (DPD) for consideration. Data sharing may be considered by the PI after due approval from IEC.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No