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PROphylaxis for paTiEnts at Risk of COVID-19 infecTion

Phase 2
Withdrawn
Conditions
COVID-19
Interventions
Registration Number
NCT04389359
Lead Sponsor
Cambridge University Hospitals NHS Foundation Trust
Brief Summary

The PROTECT open-label randomised basket trial will assess the effectiveness of hydroxychloroquine (HCQ) as chemoprophylaxis against COVID-19 in multiple vulnerable populations in the United Kingdom.

Detailed Description

COVID-19 (novel coronavirus-induced disease) was declared a global pandemic by the WHO on 11th March 2020. Currently there are no drugs proven to treat or delay progression of COVID-19 and no vaccine is yet available. Efforts are underway to repurpose established drugs with well understood drug interactions and safety profiles. Vulnerable populations such as those receiving in-centre dialysis are largely excluded from ongoing trials.

The PROTECT Basket clinical trial aims to enrol patients at particularly high risk of COVID-19 and its complications, seeking to test treatments that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening. The PROTECT trial will use innovative design and analysis methodologies to allow the simultaneous assessment of one or more treatments in multiple populations.

Patients will be eligible for recruitment to the trial if they fall within one of the following vulnerable populations: a) patients receiving in-centre haemodialysis, b) transplant patients, c) vasculitis, or d) other disease groups that may be added during the course of this trial.

PROTECT will use an innovate basket design to carry out a series of individually powered prospective, randomised comparisons in distinct vulnerable patient groups in the UK while applying Bayesian approaches to conduct pooled assessment of efficacy.

Once consented, eligible participants will be randomised to active treatment or control, stratified by PROTECT subpopulation (disease specific). Enrolment to the trial will be via an online platform and following informed consent subsequent assessments will be done via email or telephone thus reducing the burden to participants as well as reducing their exposure to COVID-19.

The master PROTECT protocol describes core components that are shared between disease specific appendices to the core protocol.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Have no previous confirmed COVID-19 diagnosis
  • Fall into one of the high risk population groups
Exclusion Criteria
  • Inability to provide informed consent
  • Symptomatic for possible COVID-19 at baseline or symptoms highly suggestive of COVID-19 experienced since 1st March 2020
  • Hypersensitivity reaction to hydroxychloroquine, chloroquine or 4-aminoquinolines or any formulation excipients
  • Contraindication to taking hydroxychloroquine as prophylaxis e.g known epilepsy
  • Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines
  • History of any retinopathy including diabetic retinopathy requiring laser therapy
  • Taking medications which are contra-indicated alongside HCQ - Digoxin, Halofantrine, Amiodarone, Moxifloxacin, Cyclosporin, Mefloquine, Praziquantel, Tamoxifen
  • Known history of prolonged QTc
  • Type I diabetes or insulin-dependent type II diabetes

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
HCQ group (dialysis)Hydroxychloroquine Sulfate 200 MGDialysis patients will receive Hydroxychloroquine sulfate 200 mg capsules or tablets (oral administration), as 600mg weekly in divided doses, given as 200mg after each dialysis session. Non-dialysis patients will receive Hydroxychloroquine sulfate, 400mg twice daily for two days, then 400mg weekly. Maximum treatment duration will be 26 weeks (6 months).
Primary Outcome Measures
NameTimeMethod
Time to confirmed diagnosis of COVID-19To study completion, average 6 months

The primary outcome for PROTECT is the time to confirmed COVID-19 infection from the date of randomisation. This will be captured via linkage with PHE or by direct reporting by sites.

Secondary Outcome Measures
NameTimeMethod
All-cause mortalityTo study completion, average 6 months

Death from any cause

Severity of COVID-19 diseaseTo study completion, average 6 months

Severity will be assessed by requirement for hospitalisation, HDU/ICU admission or death and Length of inpatient stay.

Incidence of COVID-19 complicationsTo study completion, average 6 months

Acute respiratory distress syndrome, viral pneumonitis, myocarditis/myocardial injury, acute kidney injury.

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