COVID-19
Conditions
Keywords
haemodialysis, transplant, immunosuppression, vasculitis, hydroxychloroquine, chemoprophylaxis, COVID-19
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.
Interventions
Hydroxychloroquine Sulfate administered orally for a maximum of 6 months. Doses population specific.
Sponsors
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
PROTECT will use an innovative basket design to conduct a series of prospective, randomised comparisons in multiple vulnerable patient groups in the United Kingdom with the capabilities of assessing effects within specific patients groups, and across the pooled PROTECT cohort. Additional interventions may be added as these become available. Basket Trial design brings greater efficiency, due to running multiple comparisons within one master protocol. It also allows application of innovative Bayesian analysis methods that allow adaptive borrowing of information across populations. This will mean in the case that there is a consistent effect across populations, the trial will have greater power to find significant differences for individual patient groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to confirmed diagnosis of COVID-19 | To 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
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | To study completion, average 6 months | Death from any cause |
| Severity of COVID-19 disease | To 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 complications | To study completion, average 6 months | Acute respiratory distress syndrome, viral pneumonitis, myocarditis/myocardial injury, acute kidney injury. |
Outcome results
None listed