PROphylaxis for paTiEnts at Risk of COVID-19 infecTion -V
PROTECT-V
2 other identifiers
interventional
2,240
1 country
45
Brief Summary
COVID-19 (SARS-CoV2 virus) was declared a global pandemic by the WHO on 11th March 2020. Currently there are no drugs proven to prevent COVID-19 or to reduce the severity of illness if given as prophylaxis. Although vaccines are now available, there remains a need for other prophylactic agents until vaccine use becomes widespread globally and effectiveness and durability is established, particularly in immunocompromised individuals, for whom vaccine responses may be suboptimal. Efforts are underway to repurpose established drugs with well understood drug interactions and safety profiles. PROTECT-V is a platform trial to test prophylactic interventions against SARS-CoV2 infection in vulnerable patient populations at particularly high risk of COVID-19 and its complications, seeking to identify treatments that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening. In PROTECT-V, multiple agents can be evaluated on the same platform across vulnerable populations, with the option of adding additional treatments at later time points as these become available. The expectation is for as many sites as possible to recruit to all available trial treatments at any time, however, the platform structure and randomisation/data collection systems allow sites to open the trial treatment arms according to their capacity. The trial opened with intranasal niclosamide and matched placebo, aiming to recruit 1500 vulnerable renal patients in February 2021. A parallel study protocol, was conducted in India, sponsored by The George Institute. Recruitment of around 750 Indian patients was completed in with the rest of the study arm recruitment in November 2022. The Niclosamide arm of the study was completed in June 2023. The second agent, intranasal and inhaled ciclesonide and matched placebo, was meant to be added to the platform in mid-2022 in the same renal patient population however it was unable to be included due to other factor. Sotrovimab and matched placebo have been added to the platform in August 2022 which aim to recruit approximately 800-1000 patients from the main study population with additional patient groups with primary immunodeficiency, any Haematology or Oncology patient who is currently receiving or has received chemotherapy or who is immunocompromised as a result of their disease or treatment, those with a diagnosis of an autoimmune or inflammatory disease receiving immunosuppression and also haematopoietic stem cell transplant recipients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 covid19
Started Feb 2021
Longer than P75 for phase_2 covid19
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 19, 2021
CompletedFirst Submitted
Initial submission to the registry
March 1, 2021
CompletedFirst Posted
Study publicly available on registry
May 3, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 16, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
April 16, 2025
CompletedJune 20, 2025
June 1, 2025
4.2 years
March 1, 2021
June 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Confirmed symptomatic COVID-19 infection during treatment
The primary outcome for PROTECT is confirmed symptomatic COVID-19 infection during treatment. The primary outcome event is defined as the presence of both * PCR confirmed SARS-CoV2 and * One or more symptoms in keeping with COVID-19, including: * Respiratory (Cough +/- sputum and shortness of breath) * Constitutional (Pyrexia/chills, myalgia/arthralgia, fatigue, rash, headache, confusion) * Gastrointestinal (nausea/vomiting, diarrhoea, abdominal pain, loss of appetite) The date (time) of the primary outcome event is defined as the date of the confirmed COVID-19 test.
6-9 months. Reported at 24 weeks for niclosamide and ciclesonide arms and 12 weeks for sotrovimab arm from date of IMP administration.
Secondary Outcomes (4)
Time to confirmed SARS-Cov-2 infection from the date of randomisation including asymptomatic cases. In addition, confirmed symptomatic COVID-19 infection at 16, 24, 36, and 48 weeks from date of IMP administration.
6-9 months
Safety and seriousness of the event
9 months
All-cause mortality
9 months
Severity of COVID-19 disease
28 days after date of positive test
Other Outcomes (1)
Occurrence of other infections
6-9 months
Study Arms (6)
Niclosamide
ACTIVE COMPARATORINN: Niclosamide Ethanolamine Chemical name (IUPAC): 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide.2 aminoethanol CAS registry number: 1420-04-8 Lab code: UNI911 The IMPs niclosamide Nasal Spray 1% and matching Nasal Spray Placebo will be provided in 20 mL amber glass vials with nasal spray pumps, containing 8.5 mL of the respective solution, delivering 140 μL per spray shot. It is an isotonic and euhydric aqueous solution with red colour.
Placebo niclosamide
PLACEBO COMPARATORPlacebo to match niclosamide will be supplied, stored, labelled, dispensed and dosed as for the active formulation. The placebo product is formulated to have the same appearance as the active solution.
Ciclesonide
ACTIVE COMPARATORChemical name (IUPAC): 2-\[(1S,2S,4R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9,13-dimethyl-16-oxo-5,7-dioxapentacycloicosa-14, 17-dien-8-yl\]- 2-oxoethyl 2-methylpropanoate CAS registry number: 141845-82-1 It is a pressurised solution, intended for inhalation use and commercialised under the brand Alvesco. The recommended dose of ciclesonide is 160μg once daily, which leads to asthma control in the majority of patients. However, this may be increased if necessary to 320μg twice daily, in severe asthma.
Placebo ciclesonide
PLACEBO COMPARATORMatched placebo contains the same solvent and propellant as the active product but no drug substance.
Sotrovimab
EXPERIMENTALSotrovimab, VIR-7831, GSK4182136 Sterile solution for intravenous infusion, 62.5 mg/mL, intravenous infusion Colourless or yellow to brown, liquid solution 20 mM histidine, 7% sucrose (w/v), 0.04% PS80 (w/v), 5 mM L-methionine at pH 6.0
Placebo sotrovimab
PLACEBO COMPARATORThis will be in the form of 0.9% sodium chloride 100mL for infusion and will be sourced from commercially available stock by the site. It may be procured and stored as per sites usual procedures and only requires handling as an IMP upon dispensing and labelling.
Interventions
140μL of a 1% niclosamide ethanolamine solution in each nostril twice daily, equivalent to 1.4mg of niclosamide ethanolamine salt per nostril twice daily, approximately 12 hours apart. Total daily dose 5.6mg niclosamide ethanolamine salt (4.7mg free niclosamide acid). Treatment duration will be 6-9 months or up to 28 days after COVID-19 diagnosis unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.
140μL of a matching placebo solution in each nostril twice daily. Treatment duration will be 6-9 months or up to 28 days after COVID-19 diagnosis unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.
Participants will be prescribed ciclesonide once daily, administered as follows: Two puffs (320 μg) inhaled via mouth sequentially One puff (160 μg) inhaled via nose Treatment duration will be 6-9 months or up to 28 days after COVID-19 diagnosis unless hospitalised. Participants hospitalised with a diagnosis of COVID-19 should stop the randomised treatment immediately.
There will be a single infusion of sotrovimab administered at the beginning of the study. 500mg of sotrovimab solution (8mL) will be diluted in 42mL of 0.9% sodium chloride and administered by intravenous infusion. 50mLs to be infused over 30 minutes with a 0.2 micrometre inline filter. Four vials will be required for a 2000 mg dose.
Eligibility Criteria
You may qualify if:
- Be aged 18 years or older
- Have given written informed consent
- Be a member of one of the following vulnerable patients populations
- Dialysis - including in centre haemodialysis, home haemodialysis and peritoneal dialysis
- Kidney transplant receiving at least one of the immunosuppressive medications listed below
- Vasculitis (according to Chapel Hill Consensus Conference 2012 definitions) or systemic lupus erythematosus (SLE) receiving at least one of the immunosuppressive medications listed below
- Glomerulonephritis (includes prior histological confirmation of any of the following conditions - minimal change nephropathy, focal segmental glomerulosclerosis (FSGS), IgA nephropathy, primary membranous nephropathy, membranoproliferative glomerulonephritis or lupus nephritis) receiving at least one of the immunosuppressive medications listed below Ciclosporin Tacrolimus Azathioprine Mycophenolate Mofetil or Mycophenolic Acid Belatacept Methotrexate Tocilizumab Abatacept Leflunomide Sirolimus Prednisolone (current dose) \> 20mg daily for 8 weeks Anti-TNF (infliximab, adalimumab, etanercept) Belimumab Cyclophosphamide (within the last 6 months) Rituximab (in the last 12 months) or Rituximab in the last 5 years and IgG level \<5g/l Alemtuzumab (in the last 12 months)
You may not qualify if:
- Inability to provide informed consent or to comply with trial procedures
- COVID-19 at time of enrolment - either positive SARS CoV-2 swab (PCR) or symptoms highly suggestive of COVID-19 infection
- Known chronic liver disease or hepatic dysfunction as evidenced by ALT or AST \> 3x upper limit of the normal range
- Allergy or hypersensitivity to any of the active IMPs, or to any of the excipients used
- Pregnant, trying to conceive, unwilling to use contraception or breastfeeding
- Current participation in another interventional prophylactic or vaccine trial\* against COVID-19.
- Patients remain eligible for enrolment if they have received SARS-COV-2 vaccination as part of routine care.
- Significant structural nasal disease in the opinion of the investigator
- Prior participation in the niclosamide arm of the trial (if being re-screened for participation in a second interventional arm).
- Significant structural nasal disease in the opinion of the investigator
- Prior participation in the ciclesonide arm of the trial (if being re-screened for participation in a second interventional arm).
- Currently taking inhaled corticosteroids - beclometasone dipropionate (aerosol inhaler and dry powder inhaler), budesonide (dry powder inhaler and single-dose units for nebulization), ciclesonide (aerosol inhaler), fluticasone propionate (dry powder inhaler, aerosol inhaler, and single-dose units for nebulization), mometasone furoate (dry powder inhaler).
- Received a live vaccine within last 14 days - ciclesonide increases risk of generalised infection: influenza, MMR, rotavirus, typhoid, varicella-zoster (shingles), yellow fever.
- Taking one of the following medications â—‹ Systemic Ketoconazole, itraconazole, ritanovir, nelfinavir
- Be a member of an immunocompromised population, which includes but is not limited to those groups listed in the core protocol as well as the following:
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cambridge University Hospitals NHS Foundation Trustlead
- Life Arccollaborator
- Kidney Research UK (KRUK)collaborator
- UNION therapeuticscollaborator
- Addenbrookes Charitable Trustcollaborator
- GlaxoSmithKlinecollaborator
- National Institute for Health Research, United Kingdomcollaborator
Study Sites (45)
Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
NHS Lanarkshire - University Hospital Monklands
Airdrie, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Betsi Cadwaladr University Health Board
Bodelwyddan, United Kingdom
Brighton and Sussex University Hospitals NHS Trust
Brighton, United Kingdom
North Bristol NHS Trust
Bristol, United Kingdom
West Suffolk NHS Foundation Trust
Bury St Edmunds, United Kingdom
Royal Papworth Hospital NHS Foundation Trust
Cambridge, United Kingdom
East Kent Hospitals University NHS Foundation Trust
Canterbury, United Kingdom
Cardiff & Vale University Health Board
Cardiff, United Kingdom
Epsom and St Helier University Hospitals NHS Trust
Carshalton, United Kingdom
Ayrshire & Arran NHS Trust
Crosshouse, United Kingdom
Dartford and Gravesham NHS Trust
Dartford, United Kingdom
University Hospitals of Derby and Burton NHS Trust
Derby, United Kingdom
Dorset County Hospital NHS Foundation Trust
Dorchester, United Kingdom
NHS Tayside
Dundee, United Kingdom
The Royal Devon and Exeter NHS Foundation Trust
Exeter, United Kingdom
James Paget University Hospital NHS Foundation Trust
Great Yarmouth, United Kingdom
Hull University Teaching Hospitals NHS Trust
Hull, United Kingdom
Queen Elizabeth Hospital, King's Lynn, NHS Foundation Trust
Kings Lynn, United Kingdom
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
University Hospitals of Leicester NHS Trust
Leicester, United Kingdom
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool, United Kingdom
Barts Health NHS Trust
London, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom
Royal Free NHS Foundation Trust
London, United Kingdom
St George's University Hospitals NHS Foundation Trust
London, United Kingdom
Manchester University NHS Foundation Trust
Manchester, United Kingdom
Wirral University Teaching Hospital NHS Foundation Trust
Metropolitan Borough of Wirral, United Kingdom
South Tees Hospitals NHS Foundation Trust
Middlesbrough, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
North West Anglia NHS Foundation Trust
Peterborough, United Kingdom
University Hospitals Plymouth NHS Trust
Plymouth, United Kingdom
Portsmouth Hospitals NHS Trust
Portsmouth, United Kingdom
Royal Berkshire NHS Foundation
Reading, United Kingdom
Salford Royal NHS Foundation
Salford, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, United Kingdom
The Shrewsbury and Telford Hospital NHS Trust
Shrewsbury, United Kingdom
East and North Hertfordshire NHS Trust
Stevenage, United Kingdom
South Tyneside and Sunderland NHS Foundation Trust
Sunderland, United Kingdom
The Royal Wolverhampton NHS Trust
Wolverhampton, United Kingdom
York Teaching Hospital NHS Foundation Trust
York, United Kingdom
Related Publications (2)
Humphrey TJL, Qian W, Chen-Xu M, Dowling F, Gatley K, Adhikari R, Hensman T, Stockley L, Bassi A, Bathla N, Dasgupta I, Dosanjh DPS, Jellingso M, Sorensen P, Jensen ML, Callesen AW, Bradley JR, Jha V, Sommer MOA, Hiemstra TF, Smith RM; PROTECT-V consortium. Prophylaxis for renal patients at risk of COVID-19 infection: results from the intranasal niclosamide randomised, double blinded, placebo controlled arm of the PROTECT-V platform trial. BMC Infect Dis. 2025 Feb 11;25(1):204. doi: 10.1186/s12879-025-10584-4.
PMID: 39934669DERIVEDHumphrey TJL, Dosanjh D, Hiemstra TF, Richter A, Chen-Xu M, Qian W, Jha V, Gatley K, Adhikari R, Dowling F, Smith RM. PROphylaxis for paTiEnts at risk of COVID-19 infecTion (PROTECT-V). Trials. 2023 Mar 13;24(1):185. doi: 10.1186/s13063-023-07128-z.
PMID: 36915199DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rona Smith, Dr
Cambridge University Hospitals NHS Foundation Trust
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- PROTECT-V will be a double blind placebo controlled study where neither the participant nor clinician will be aware of treatment allocation.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Senior Research Associate
Study Record Dates
First Submitted
March 1, 2021
First Posted
May 3, 2021
Study Start
February 19, 2021
Primary Completion
April 16, 2025
Study Completion
April 16, 2025
Last Updated
June 20, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Beginning 9 months and ending 36 months following article publication.
- Access Criteria
- Proposals may be submitted up to 36 months following article publication and after 36 months the data will be available in our University's data warehouse however without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at the link below
Anonymized individual participant data meta-analysis that underlie the results reported in this article would be shared with investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.