PROTECT [COVID-19] [UPH]
Research type
Research Study
Full title
PROphylaxis for paTiEnts at risk of COVID-19 infecTion
IRAS ID
288652
Contact name
Rona Smith
Contact email
Sponsor organisation
Cambridge university Hosptials NHS Foundation Trust and University of Cambridge
Eudract number
2020-004144-28
ISRCTN Number
ISRCTN88057279
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 1 months, 16 days
Research summary
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 prevent COVID-19 or to reduce the severity of illness if given as prophylaxis. There is also no vaccine for SARS-CoV-2. Efforts are underway to repurpose established drugs with well understood drug interactions and safety profiles.
A number of clinical trials have been established at great speed following the onset of the pandemic (e.g.PRINCIPLE,RECOVERY) but none of these are enrolling participants with significantly reduced kidney function and/or receiving certain kinds of immunosuppressive medicines such as solid organ transplant recipients.
The PROTECT clinical trial aims to enrol patients at particularly high risk of COVID-19 and its complications, seeking to test the use of nasal nicolosamide treatment as a prophylactic measure that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening. PROTECT is a randomised, double blind, placebo controlled event driven trial.
Patients will be eligible for recruitment to the trial if they fall within one of the following vulnerable populations: a)patients receiving dialysis, b)kidney transplant patients, c)patients with vasculitis or glomerulonephritis.
A total of 1500 participants will be randomised to active treatment or placebo, stratified by PROTECT sub-population, age and participating sites. Enrolment to the trial will be via an online platform following informed consent with a face to face screening visit. Subsequent assessments, aside from an in person end of trial visit, will be done via email or telephone together with utilising the routine collected health data thus reducing the burden to participants as well as reducing their exposure to COVID-19.
Summary of study results:
Sotrovimab lay summary:
Despite covid vaccinations, some people do not have a strong enough immune system to make a protective response and fight off infections, this is known as being immunocompromised. There remains a need for medicines, in addition to vaccines, that can protect patients that have a poor immune system from being infected with covid. The PROTECT-V trial looked at several medications in this group of patients. Sotrovimab is a medicine specifically developed as a treatment for COVID.In the trial, patients were given either Sotrovimab or placebo “dummy drug” through an infusion into a vein. Neither the patient nor their doctor knew which one they received. Patients continued to receive their normal medicines and any vaccinations, and were seen regularly by their doctor over a 48 week period. The main result of this trial was based on whether a patient had a positive covid test or not, within 12 weeks of taking the trial medication.
619 participants entered the trial and 588 of them received either Sotrovimab or placebo. The average age of participants was 64. After 12 weeks, 21 people in the placebo group and 17 people in the sotrovimab group developed covid with symptoms. Four people were admitted to hospital with covid (3 in the placebo group; 1 in the Sotrovimab).
In the trial, Sotrovimab was safe and well tolerated, but it did not change how quickly the virus cleared from their bodies if they became infected.
The trial found that sotrovimab did not prevent COVID better than placebo. There were hints of a benefit early in the trial, before a new covid type called JN.1 became common in the UK. There remains an ongoing need to better protect vulnerable immunosuppressed people from COVID and other viruses, which is particularly challenging when new variants of the virus rapidly appear.
Niclosamide lay summary:
Despite covid vaccinations, people with kidney disease often do not have a strong enough immune system to make a protective response, and to fight off the infection if they get it. There remains a need for medicines to protect patients that have poor immune systems before being exposed to covid. The PROTECT-V trial looked at several medications to use in this group of patients.Patients were given either the trial medicine, Niclosamide, or a placebo “dummy medicine” through a nose spray, taken twice a day for 9 months, or until they developed a covid infection, whichever happened sooner. Neither the patient nor their doctor knew which one the patient received. Those who got COVID but were well enough to stay at home continued the medicine for another 4 weeks, but if they were sick enough to need to be admitted to hospital they stopped the trial medication and could receive any available treatment for COVID.
The trial recruited patients in UK (1233 individuals) and India (420 individuals). Of those, 1588 (795 niclosamide and 793 placebo) patients received at least one dose of their allocated trial treatment. 61% of patients were 60 years old or more. 64% of patient were male. Overall, 37% of patients in the niclosamide group compared to 20% in the placebo group stopped taking the nasal spray due to it causing irritation of the nose. 236 covid infections were reported during in the trial; 103 in the niclosamide group and 133 in the placebo group.
Despite fewer infections in patients receiving niclosamide, many more people in that group stopped taking the medicine early, and so the trial did not show that niclosamide nasal spray reduced the risk of symptomatic covid infection in patients with kidney disease when compared to placebo. Niclosamide nasal spray was safe but not well tolerated due to local nasal irritation.
Although the trial result was negative, it importantly recruited many patients with kidney disease who are often excluded from trials. It also showed the strength of international collaboration between charities, drug company partners and medical doctors and researchers.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
20/SC/0403
Date of REC Opinion
23 Oct 2020
REC opinion
Favourable Opinion