Hydroxychloroquine Chemoprophylaxis for COVID-19 Infection in High-risk Healthcare Workers.

Efficacy and Safety of Hydroxychloroquine in Primary Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers at Risk of Exposure: Randomised Control Trial

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.

Study Overview

• Status: Unknown
• Conditions: Healthcare Workers; SARS-CoV-2
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Placebo oral tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 374
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; 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.	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 Names: HCQ
Placebo Comparator: Control group; 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of SARS-CoV-2 as determined by negative RT-PCR at the end of 12 week study period	Negative RT-PCR for SARS-CoV-2 both at baseline and at end of 12 weeks in experimental arm	From date of randomization until study completion 12 weeks after treatment initiation
Safety as determined by presence or absence of any adverse event related with hydroxychloroquine treatment	To assess the presence or absence of side effects from HCQ treatment.	From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed SARS-CoV-2 infection based on symptoms and confirmed by RT-PCR	Symptomatic infection by SARS-CoV-2 defined as cough, dyspnea, fever, myalgia, arthralgia or rhinorrhea.	From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation
Clinical disease severity in confirmed SARS-CoV-2 participants	Disease severity including i) asymptomatic. ii) Mild symptoms but ambulatory. iii) Moderate symptoms requiring hospitalisation. iv) severe symptoms requiring ICU care and oxygen. v) Severe symptoms requiring assisted mechanical ventilation. vi) Death.	From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation
Incidence of any acute respiratory infection	Symptomatic non-COVID viral infection (any other acute respiratory illness with fever but without evidence of epidemiological risk factors such as close contact with SARS-CoV-2 positive patient or travel to or residence in high-risk area).	From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation

Collaborators and Investigators

• Sponsor: Services Institute of Medical Sciences, Pakistan
• Investigators: Principal Investigator: Saira Burney, FRCP (Edin), SIMS

Study record dates

Study Major Dates

• Study Start (Anticipated): May 15, 2020
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): October 15, 2020

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): April 30, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; prophylaxis; HCQ; healthcare workers
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 16082019

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