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

TL;DR

A study tested if intranasal niclosamide could protect renal patients from COVID-19 but found no significant benefit compared to placebo.

Contribution

This is the first randomized, placebo-controlled trial evaluating intranasal niclosamide as prophylaxis for renal patients at risk of COVID-19.

Findings

Intranasal niclosamide did not reduce the risk of symptomatic COVID-19 infection compared to placebo.

The study observed a high withdrawal rate due to local upper airway irritation in the niclosamide group.

Most participants had received prior vaccination, but the drug did not provide additional protection.

Abstract

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.

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.

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)).

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

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.

The online version contains supplementary material available at 10.1186/s12879-025-10584-4.

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