Healthcare personnel are at an increased risk of exposure to SARS-CoV-2 infection while handling such patients. Currently, there is no treatment available for SARS-CoV-2 and stringent preventive measures are advised to avoid or minimize risk of exposure to healthcare workers. There are in vitro studies available which show inhibition of corona virus by hydroxychloroquine, a widely-used agent against malaria and certain autoimmune conditions and of low-cost and limited toxicity. However, evidence regarding its effects in patients is limited. We plan to conduct a randomized controlled trial to evaluate the safety and potential prophylactic efficacy of hydroxychloroquine in preventing secondary SARS-CoV-2 infection among healthcare workers at high-risk of exposure while managing such patients.
An interventional randomised control trial that will include 374 participants who will be
healthcare workers at variable risks of exposure to SARS-CoV-2 while managing patients both
suspected and confirmed with COVID-19 infection.Each participant will undergo detailed
clinical evaluation to confirm eligibility, complete blood count, retinal imaging and ECG
rhythm lead at baseline. A nasopharyngeal swab for reverse-transcriptase-polymerase chain
reaction (RT-PCR) will also be taken. The enrolled participants will be randomised to two
treatment arms with the experimental arm receiving Tab.Hydroxychloroquine (HCQ) 400mg twice a
day on day 1 followed by 400mg weekly for 11 weeks. The placebo comparator arm will receive 2
tablets twice daily on day 1 followed by 2 tablets weekly for 11 weeks. The participants will
be followed up via phone call weekly to ensure drug compliance, occurrence of drug-related
side effects or respiratory symptoms. The final visit 4 will mark the end of study at 12
weeks from randomisation when a repeat nasopharyngeal swab for SARS-CoV-2 RT-PCR will be
taken.The primary outcome measures will be prevention of SARS-CoV-2 infection as determined
by a negative RT-PCR in the experimental arm at the end of 12 weeks and HCQ safety as
determined by occurrence of adverse events.
Drug: Hydroxychloroquine
Health care workers at high risk of contracting SARS-CoV-2 randomized to this arm will be treated with oral hydroxychloroquine 400 mg twice a day (four 200 mg tablets) on day 1 followed by 400mg (two 200 mg tablets) once a week for 11 weeks.
Other Name: HCQ
Drug: Placebo oral tablet
• Health care workers at high risk of contracting SARS-CoV-2 randomized to this arm will be treated with placebo twice a day (four tablets) on day 1 followed by 2 tablets once a week for 11weeks.
Inclusion Criteria:
- Adult healthcare workers all genders ≥ 18 to ≤ 60 years of age upon study consent.
- Healthcare workers (doctors and nurses) at Services hospital, Lahore considered work
at high-risk of SARS-CoV-2 exposure (defined below):
- Healthcare workers in Corona triage areas.
- Healthcare workers in Corona Isolation Units.
- Healthcare workers in Corona ICUs.
- Healthcare workers in general medical wards.
- Healthcare workers in general surgical wards.
- Healthcare workers in other units not directly dealing with suspected Corona
patients e.g. Endocrinology department
- Afebrile with no constitutional symptoms.
- No household contact with confirmed active SARS-CoV-2 infection in the last 3 weeks.
- Negative PCR at visit 0.
- Willing and able to comply with scheduled visits, treatment plan, and other study
procedures.
- Willing to not take any other medicines especially fluoroquinolones and macrolides for
the duration of study.
- Signed informed consent, demonstrating that the subject understands the interventions
required for the study and the purpose of the study.
Exclusion Criteria:
- Participation in other investigational clinical trials for the treatment or prevention
of SARS-CoV-2 infection within 30days.
- Subjects unwilling to practice at least one highly effective method of birth control
for the duration of the study.
- Having a prior history of blood disorders such as aplastic anemia, agranulocytosis,
leukopenia, or thrombocytopenia or prior history of glucose-6-phosphate dehydrogenase
(G-6-PD) deficiency.
- Having H/O skin disorders e.g. dermatitis, psoriasis or porphyria.
- Taking any of the following medication:
- Anti-arrythmic agents including digoxin.
- GI drugs including antacids, proton-pump inhibitors, cimetidine.
- Anti-cancer treatment including methotrexate, cyclosporin.
- Anti-diabetic agents including insulin.
- Corticosteroids.
- Drugs causing QT interval prolongation especially antidepressants,
anti-epileptics and macrolides.
- Drugs affecting electrolyte balance including diuretics, laxatives.
- Drug allergies: 4-Aminoquinolines.
- Pre-existing retinopathy/maculopathy of the eye.
- Known chronic liver disease or cirrhosis, including hepatitis B and/or untreated
hepatitis.
- Previous history of severe hypoglycaemia.
- Known case of renal disease.
- Untreated or uncontrolled active bacterial, fungal infection.
- Known or suspected active drug or alcohol abuse.
- Women who are pregnant or breastfeeding.
- Known hypersensitivity to any component of the study drug.
- A known history of prolonged QT syndrome or history of additional risk factors for
arrythmias (e.g., heart failure, family history of Long QT Syndrome).
- Known H/O respiratory disorders e.g. asthma, chronic obstructive pulmonary disease.
Saira Burney, FRCP (Edin)
923014226617
dr_syra@hotmail.com
Khadija I Khawaja, FCPS
923009495896
khadijairfan@gmail.com
Saira Burney, FRCP (Edin), Principal Investigator
SIMS