PROphylaxis for paTiEnts at Risk of COVID-19 infecTion (PROTECT)
Primary Purpose
COVID-19
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Hydroxychloroquine Sulfate 200 MG
Sponsored by
About this trial
This is an interventional prevention trial for COVID-19 focused on measuring haemodialysis, transplant, immunosuppression, vasculitis, hydroxychloroquine, chemoprophylaxis, COVID-19
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
HCQ group (dialysis)
Control
Arm Description
Dialysis 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).
Patients will continue with their usual medicines and clinical care without additional HCQ.
Outcomes
Primary Outcome Measures
Time to confirmed diagnosis of COVID-19
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
All-cause mortality
Death from any cause
Severity of COVID-19 disease
Severity will be assessed by requirement for hospitalisation, HDU/ICU admission or death and Length of inpatient stay.
Incidence of COVID-19 complications
Acute respiratory distress syndrome, viral pneumonitis, myocarditis/myocardial injury, acute kidney injury.
Full Information
NCT ID
NCT04389359
First Posted
May 12, 2020
Last Updated
March 4, 2021
Sponsor
Cambridge University Hospitals NHS Foundation Trust
Collaborators
University of Cambridge
1. Study Identification
Unique Protocol Identification Number
NCT04389359
Brief Title
PROphylaxis for paTiEnts at Risk of COVID-19 infecTion
Acronym
PROTECT
Official Title
PROphylaxis for paTiEnts at Risk of COVID-19 infecTion (PROTECT): a Basket Trial of Prophylactic Interventions Amongst At-risk Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Regulatory approvals not received
Study Start Date
September 2020 (Anticipated)
Primary Completion Date
August 2021 (Anticipated)
Study Completion Date
August 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cambridge University Hospitals NHS Foundation Trust
Collaborators
University of Cambridge
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
haemodialysis, transplant, immunosuppression, vasculitis, hydroxychloroquine, chemoprophylaxis, COVID-19
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HCQ group (dialysis)
Arm Type
Experimental
Arm Description
Dialysis 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).
Arm Title
Control
Arm Type
No Intervention
Arm Description
Patients will continue with their usual medicines and clinical care without additional HCQ.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine Sulfate 200 MG
Other Intervention Name(s)
Plaquenil
Intervention Description
Hydroxychloroquine Sulfate administered orally for a maximum of 6 months. Doses population specific.
Primary Outcome Measure Information:
Title
Time to confirmed diagnosis of COVID-19
Description
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.
Time Frame
To study completion, average 6 months
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
Death from any cause
Time Frame
To study completion, average 6 months
Title
Severity of COVID-19 disease
Description
Severity will be assessed by requirement for hospitalisation, HDU/ICU admission or death and Length of inpatient stay.
Time Frame
To study completion, average 6 months
Title
Incidence of COVID-19 complications
Description
Acute respiratory distress syndrome, viral pneumonitis, myocarditis/myocardial injury, acute kidney injury.
Time Frame
To study completion, average 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Hiemstra, PhD
Organizational Affiliation
Cambridge University Hospitals NHS Foundation Trust
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
PROphylaxis for paTiEnts at Risk of COVID-19 infecTion
We'll reach out to this number within 24 hrs