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
Authors: Humphrey Toby J. L. , Qian Wendi , Chen-Xu Michael , Dowling Francis , Gatley Katrina , Adhikari Rakshya , Hensman Tracey , Stockley Louise , Bassi Abhinav , Bathla Nikita , Dasgupta Indranil , Dosanjh Davinder P. S. , Jellingsø Mads , Sørensen Per , Jensen Morten Lind , Callesen Anne Weibel , Bradley John R. , Jha Vivekanand , Sommer Morten O. A. , Hiemstra Thomas F. , Smith Rona M. ,   PROTECT-V consortium, Alchi Bassam , Alejmi Abdulfattah , Basu Neil , Bebb Charlotte , Bell Samira , Bhargava Anudita , Bhandari Sunil , Bingham Coralie , Bramham Kate , Caskey Fergus , Chand Sourabh , Chaudhry Dhruva , Chaudhury Arpita Ray , Chennamsetty Sashidhar , Chitalia Nihil , Chowdhury Paramit , Curran Simon , Davies Simon , Davison Rachel , Delaney Michael , Dey Vishal , Dick Jonathan , Eid Mahmoud , El-Damanawi Ragada , Fluck Sarah , Gama Rouvick , Goldsmith Christopher , Gkrania-Klotsas Effrossyni , Griffin Sian , Hull Richard , Ignatius Avinash , Jayne David , Jones Colin , Kamalnathan Manivarma , Kolhe Nitin , Lafont Tanguy , Lambie Mark , Lawman Sarah , Ledson Thomas , Lightstone Liz , Lucas Bethany , Mahalingasivam Viyaasan , Mark Patrick , McAdoo Stephen , McCafferty Kieran , Patrick Jean , Prasad Narayan , Pritchard Nicholas , Rainone Francesco , Ramachandran Raja , Rathore Vinay , Sahay Manisha , Salama Alan , Saxena Sanjiv , Shah Sapna , Sharpe Claire , Spencer Sebastian , Taylor Jo , Trotter Patrick , Udayaraj Udaya , Ugni Shiva , Wade Josh , Wahba Mona , Wason James , Wilkie Martin , Wilkinson Ian 
Published: February 2025

Abstract

Purpose
Despite vaccination, many patients remain vulnerable to COVID-19 infection and poorer outcomes, because of underlying health conditions resulting in sub-optimal vaccine responses. This study aims to demonstrate whether intranasal niclosamide confers additional protection against COVID-19 infection above standard preventative measures including vaccination.

Methods
PROTECT-V (PROphylaxis for paTiEnts at risk of COVID-19 infecTion) is a platform trial testing multiple pre-exposure COVID-19 prophylactic agents in vulnerable patients. This paper reports results from the randomised, double blind, placebo controlled intranasal niclosamide arm.
1651 adult patients on dialysis, with a kidney transplant or renal autoimmune conditions on immunosuppression were randomised from 48 sites (37 UK; 11 Indian). Intranasal niclosamide or matched placebo was administered twice daily, for up to nine months. Primary outcome was time to symptomatic COVID-19 infection.

Results
1651 patients were randomised (826 niclosamide;825 placebo) between February 2021 to November 2022. 655(39.7%) were dialysis patients, 622(37.7%) kidney transplant recipients and 374(22.7%) had renal autoimmune disease. 97.5% patients in the UK and 66.4% patients in India with comparable proportions in both treatment groups had received COVID-19 vaccinations. Despite no adverse safety signal, there was a high withdrawal rate (40% niclosamide;23.8% placebo) due to local upper airway irritation leading to a significantly shorter treatment duration in the niclosamide group). Symptomatic COVID-19 infection during study treatment was observed in 103 patients in the niclosamide group and 133 in the placebo group (estimated hazard ratio 1.02(95%CI 0.79–1.32)).

Conclusion
Intranasal niclosamide did not reduce risk of symptomatic COVID-19 infection in this cohort compared to placebo.

Trial Registration
This study is registered with ClinicalTrials.gov: NCT04870333 (submitted 01/03/2021; posted 03/05/2021), EudraCT: 2020–004144-28 and the Clinical Trials Registry of India (CTRI):#CTRI/2022/03/040802.