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

Not Applicable

• Conditions: SARS-CoV-2; Healthcare Workers
• Interventions: Drug: Placebo oral tablet; Drug: Hydroxychloroquine

• Registration Number: NCT04370015
• Lead Sponsor: Services Institute of Medical Sciences, Pakistan

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-04-27
• Study First Submitted QC: 2020-04-29
• Study First Posted: 2020-04-30
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-04
• Last Update Posted: 2020-05-06
• Study Start: 2020-05-15
• Primary Completion: 2020-06-30
• Study Completion: 2020-10-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 374

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	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.
Treatment group	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of any acute respiratory infection	From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation	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).
Confirmed SARS-CoV-2 infection based on symptoms and confirmed by RT-PCR	From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation	Symptomatic infection by SARS-CoV-2 defined as cough, dyspnea, fever, myalgia, arthralgia or rhinorrhea.
Clinical disease severity in confirmed SARS-CoV-2 participants	From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation	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.