Hydroxychloroquine has been approved by FDA as one of the treatment options for COVID 19.Healthcare personnel are amongst those at highest risk to contract the disease. Several health authorities are now recommending the use of hydroxychloroquine as pre-exposure prophylaxis is in health care personnel. Several studies are on going in this context. However there is a controversy regarding the dosage regimen. This drug has a half life of 22.4 days. In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.
Study design:
Phase 2 proof of concept study Study Type: Interventional (Clinical Trial) Estimated
Enrollment : at least 200 participants Since the investigators have no current data on
pre-exposure prophylaxis to calculate sample size statistically, so a minimum of 50
participants in each arm will be recruited including 20% attrition rate. The investigators
will be recruiting a minimum of 200 participants in the study , that is at least 50 in each
of the four arms.
Allocation: Randomized Intervention Model: Parallel Assignment Study model: Parallel group
interventional study Location: SZABMU/PIMS Study duration: a minimum of 12 weeks from
recruitment
Materials and Methods:
Participants will be recruited after approval from Ethical Review Board .A written informed
consent will be taken from all participants. Participants fulfilling the eligibility criteria
will be randomized to 4 arms.
Arm Intervention /treatment
Experimental group 1: Hydroxychloroquine 400 mg twice a day 1,followed by 400 mg weekly for a
total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral
Experimental group 2:Hydroxychloroquine 400 mg on day 1 followed by 400mg once every 3 weeks
for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral
Experimental group 3:Hydroxychloroquine 200 mg on day 1 followed by 200 mg once every 3 weeks
for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral
Control Group : Placebo 200mg will be given on day 1 followed by Placebo 200mg every three
weeks for a total of 12 weeks.
Base line characteristics of all participants will be recorded including age ,gender,role of
healthcare personnel, comorbidities, and drugs the participant is using.
Samples will be collected for complete picture blood, liver and renal function tests and
electrocardiogram. These tests will also be conducted every month till the end of the trial
and the participants will be monitored for any adverse effects.
During the study duration all participants will self- report any symptoms related to COVID 19
and any adverse reactions from the drug. Participants having COVID 19 symptoms at any time
will be tested by the gold standard test PCR for SARS-COV-2 using nasopharyngeal and
oropharyngeal swabs.
All participants at the end of the study will have PCR for SARS-COV-2 and if available IgM
and IgG serology to find out if they had any infection, did not get infected at all or only
had asymptomatic or mild infection.
Drug: Hydroxychloroquine Sulfate 200 MG
Hydroxychloroquine Sulphate 200 mg tablets will be prescribed and instituted orally at the doses and regimens described
Other Name: Tab HCQ
Other: Placebo
Control group will receive a Placebo tablet. Placebo 200mg will be given on Day 1 followed by Placebo 200mg every three weeks.
Inclusion Criteria after taking a written informed consent:
- A healthcare worker at high risk for COVID19 exposure (defined below):
- Persons primarily working in emergency departments (physicians, nurses, ancillary
staff, triage personnel) ;
- Persons primarily working in intensive care units (physicians, nurses, ancillary
staff, respiratory therapists) ;
- Persons performing aerosol generating procedures (i.e. anesthesiologists, nurse
anesthetists, gastroenterologists performing endoscopy, Pulmonologists performing
bronchoscopy);
- First responders (i.e. EMTs, paramedics) ;
- Persons working in the departments of General Medicine, Pulmonology, Infectious
disease and Isolation wards.
Exclusion Criteria:
- Active COVID-19 disease;
- Confirmed prior COVID-19 disease;
- Current fever, cough, shortness of breath;
- Contraindication or hypersensitivity to chloroquine or hydroxychloroquine ad
hypersensitivity to 4-aminoquinoline compounds;
- Pregnancy;
- Lactation;
- Prior retinal eye disease;
- Known Chronic Kidney disease, Stage 4 or 5 or dialysis;
- Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency ;
- Weight <40 kg;
- Current use of chloroquine,hydroxychloroquine or cardiac medicines like flecainide,
amiodarone, digoxin, procainamide, or propafenone;
- Current use of medications with known significant drug-drug interactions: artemether,
lumefantrine, mefloquine, tamoxifen or methotrexate;
- Current use of medications causing QT interval prolongation like:
macrolides,antipsychotics,quinolones,antihistamines,SSRIs,tricyclic antidepressants,
antifungals;
- Recent Myocardial Infarction;
- History of Epilepsy
Shaheed Zulfiaqar Ali Bhutto Medical University
Islamabad, Federal Capital, Pakistan
Investigator: Fibhaa Syed, FRCP
Contact: +923335300002
fibhaasyed@gmail.com
Fibhaa Syed, FRCP
+923335300002 - +923335300002
drfibhasyed@szabmu.edu.pk
Mohammed Ali Arif, FRCP
+923335123701 - +923335123701
mohammad_ali_arif@hotmail.com