Clinical trial NCT04370015: Hydroxychloroquine Chemoprophylaxis for COVID-19 Infection in High-risk Healthcare Workers.
Official title: Efficacy and Safety of Hydroxychloroquine in Primary Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers at Risk of Exposure: Randomised Control Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: SARS-CoV-2
Healthcare Workers
Keywords: SARS-CoV-2
HCQ
prophylaxis
healthcare workers
Lead sponsor: Services Institute of Medical Sciences, Pakistan
Sponsor class: OTHER_GOV
First posted: 2020-04-30
Enrollment: 374
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel assignment
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prevention of SARS-CoV-2 as determined by negative RT-PCR at the end of 12 week study period
timeFrame: From date of randomization until study completion 12 weeks after treatment initiation
measure: Safety as determined by presence or absence of any adverse event related with hydroxychloroquine treatment
timeFrame: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation
Secondary outcomes:
measure: Confirmed SARS-CoV-2 infection based on symptoms and confirmed by RT-PCR
timeFrame: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation
measure: Clinical disease severity in confirmed SARS-CoV-2 participants
timeFrame: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation
measure: Incidence of any acute respiratory infection
timeFrame: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation
Other outcomes:
Locations:
Study officials:
affiliation: SIMS
name: Saira Burney, FRCP (Edin)
role: PRINCIPAL_INVESTIGATOR
References: