A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis – ICE COVID (preprint)

ABSTRACT

Introduction: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in-vitro activity against SARS-CoV-2. This clinical trial was designed to investigate the efficacy of carrageenan nasal and throat sprays in reducing the rate and severity of COVID-19 infection. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Methods: and analysis: A single centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 11 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water) or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks.Primary outcome: Acquisition of COVID-19 infection as confirmed by positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. Hypothesis: That carrageenan spray will reduce SARS-CoV-2 attachment to the naso- and oropharyngeal mucosal epithelial cells thus reducing the effective viral infective dose preventing COVID19 infection and reducing disease severity where infection is not prevented. Ethics and dissemination Ethics approval was obtained from Research Ethics Committee 6 South Wales (REC Reference 20/WA/0298; IRAS 283187) on the 18 th November 2020. The results will be submitted for publication in a peer-reviewed journal. Trial registration number NCT04590365; registered on ClinicalTrials.gov (NCT04590365) on the 19 th October 2020.