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

Background and rational of the study:

Novel corona virus (SARS-CoV-2) epidemic which stared from Wuhan in China is now a well
established pandemic worldwide affecting more than 3 lakh people with more than 15000
mortality. As Italy, Spain, Germany, United Kingdom and USA have taken over from China in
term of highest burden of mortality, India is at the edge of becoming the next epicentre of
this Pandemic. Presently there are around 500 active cases of corona virus disease-19
(COVID-19) in India with unfortunate mortality of 8 patients as on 24th March 2020. The
clinical presentation of the COVID-19 varies from asymptomatic cases and mild symptoms of
fever, cough, sore throat, headache, myalgia, nasal congestion, diarrhea to severe pneumonia,
acute respiratory distress syndrome (ARDS) requiring mechanical ventilation and even
multi-organ dysfunction syndrome (MODS), sepsis leading to death. If adequate preventive and
therapeutic measures are not taken, India has very high risk of affecting million of 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 are 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.

Presently many scientist and doctors are recommending many existing available drugs
(Ribavirin, lopinavir, Remdesivir, chloroquine, hydroxychloroquine) for SARS-CoV-2 infection
for therapeutic and as well as prophylactic purpose . Among which hydroxychloroquine sulphate
(HCQ), a chloroquine analogue has given some rays of hope to battle against this deadly
pandemic. In a in vitro study researchers have found that HCQ has some anti viral effect
against SARS-CoV through mechanism targeted at the host cell. HCQ is quite safe drugs as it
is being used in rheumatology patients for lifelong therapy 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 including USA and India have already endorse
that due to lack of any other better alternative drugs. 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 labarotory confirmed COVID-19 cases. But there is still
lack of significant scientific data to prove or disprove the efficacy of HCQ for the
treatment and post exposure chemo-prophylaxis for SARS-CoV-2 infection management. Being a
tertiary care centre we are catering many states which include Punjab, hariyana, himachal
Pradesh, Uttara khand, Uttar Pradesh. Among this Punjab have highest population of non
residential Indian (NRI) and most of them have returned home. This put our institute to
handle highest burden of suspected cases of SARS-CoV-2 in northern India. So we have planned
this randomised control clinical trial to evaluate the efficacy of post exposure prophylaxis
(PEP) with HCQ for the prevention of COVID-19 in asymptomatic population who are at risk for
SARS-CoV-2 infection. As a research institute of national as well as international interest,
it is a great opportunity for us to produce such a robust data which can be utilized in
reforming national and international guidelines for the battle against of COVID-19 pandemic.

Details of method:

Aims of the study: To evaluate the efficacy of post exposure prophylaxis (PEP) with HCQ for
the prevention of COVID-19 in asymptomatic individual who are at risk for SARS-CoV-2
infection.

Site of Study: The study will be conducted in the special screening OPD for the SARS-CoV-2 at
Emergency and medical outpatient department (EMOPD & MOPD) and Communicable disease ward of
the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
The study will be done under the collaboration of the department of Internal Medicine,
Virology and Pharmacology of the institute, PGIMER,Chandigarh.

Study Design: It is an open label controlled clinical trial. The study will be done in two
groups. After screening of the suspected SARS-CoV-2 infected individuals, asymptomatic
quarantined individuals will be assigned into two study groups. Post exposure prophylaxis
(PPE) 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 not receive
HCQ. Both the groups will receive standard care of therapy. Individual who will not give
consent for HCQ prophylaxis and those with contraindication for HCQ therapy will be directly
included in the control group. They will be followed up for 4 weeks telephonically or
physically as and when required.

Screening and Enrolment of Patients: All the suspected cases of COVID-19 will be screened as
per ICMR guideline at special screening OPD for the SARS-CoV-2 at Emergency and medical
outpatient department (EMOPD & MOPD. All asymptomatic individuals who have undertaken
international travel in last 2 weeks and all asymptomatic individual with direct contact with
laboratory confirmed cases will be advised for home quarantine for 2 weeks along with social
distancing and personal hygiene. They will be given the option for taking HCQ prophylaxis.
They will be assigned into one post exposure prophylaxis (PEP) group and one control croup as
per inclusion and exclusion criteria after getting informed consent.Individual who will not
give consent for HCQ prophylaxis and patients 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 directly included in the
control groups.