ICE-COVID: Carrageenan Nasal Spray for COVID-19 Prophylaxis

Sponsor

Swansea University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04590365

Collaborator

Cardiff University (Other), Marinomed Biotech AG (Industry), Walgreens Boots Alliance (Other), Abertawe Bro Morgannwg University Health Board (Other)

480

Enrollment

Location

Arms

23.5

Anticipated Duration (Months)

20.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The current COVID-19 pandemic is the biggest global healthcare challenge in the last century, and the number of cases in the next 12 months is likely to increase. There is currently no proven treatment, chemoprophylaxis or vaccine against COVID-19, which exhibits a wide clinical spectrum from asymptomatic carriage to mild upper respiratory tract infection, severe viral pneumonia to acute respiratory distress syndrome and death. Key workers are at high risk of exposure highlighting the need for effective preventative strategies.

SARS-CoV-2 is a positive-sense single-stranded enveloped RNA virus which transmits via droplets, aerosols and direct contact, to reach their target naso- and oropharyngeal epithelial cells through initial electrostatic interactions to cell surface heparan sulphate (HS) proteoglycans. Carrageenan mimics cell surface HS, thereby trapping the virus to allow mucociliary clearance and has demonstrated anti-viral activity in-vitro and in a number of common cold clinical trials when administered as a nasal spray.

ICE-COVID a randomised, double blind, placebo-controlled phase III trial of the prophylactic efficacy of iota-carrageenan nasal and throat spray in preventing COVID-19 illness in at risk healthcare professionals. Participants (n=240) will be randomly allocated to either the treatment arm (verum Coldamaris plus, 0.12% iota-carrageenan plus 0.04% Kappa-Carrageenan in 0.5% saline) or placebo (Coldamaris sine, saline 0.5%) arm. The study's primary objective is the prevention of COVID-19 infection, confirmed by PCR swab or documented seroconversion. Secondary objectives are to determine if carrageenan sprays reduce the clinical severity of COVID-19 and symptomatic acute respiratory infection of other aetiologies (non-SARS-CoV-2).

Condition or Disease	Intervention/Treatment	Phase
COVID-19 SARS-CoV 2	Device: Carrageenan nasal and throat spray Device: Saline nasal and throat spray	N/A

Detailed Description

Objectives:

The primary objective is to determine whether carrageenan nasal and throat sprays reduce the risk of COVID-19 infection.

The secondary objectives are:

To determine whether carrageenan nasal and throat spray reduces the severity and/or duration of COVID-19 infection;
To determine whether carrageenan nasal and throat spray reduces the risk of infection with other respiratory viruses
To determine whether carrageenan nasal and throat spray reduces the severity and/or duration of infection with other respiratory viruses
To determine the usability of carrageenan nasal and throat spray for long term prophylaxis against respiratory viruses
To determine the effect on of using the spray on quality adjusted life years and cost effectiveness

Study Design:

The study design consists of a double blind, randomised placebo-controlled trial. Of the 480 healthcare professionals recruited, 240 participants will be randomly allocated to each of either the treatment arm (verum Coldamaris plus i.e. Iota-carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline) or placebo (Coldamaris sine i.e. 0.5% saline) arms. Participants will use the spray prophylactically into each nostril and throat three times per day for 8 weeks, during which time the participants will be invited to complete a daily symptom tracker questionnaire. COVID-19 infection during the trial period will be confirmed using viral PCR swabs (if symptomatic), SARS-CoV-2 serology at 14 days following onset of symptoms as well as trial entry and exit serology to detect asymptomatic infection during the study period.

Allocation to each group, treatment or placebo administration and data analysis will be blinded to both participant and investigator. The primary outcome measure will be acquisition of COVID-19 infection as confirmed by positive PCR swab taken at the time of symptoms or positive serology measured 2 weeks after symptom onset or seroconversion at the end of the trial (via trial entry and exit serology) to detect asymptomatic infection during the study period. Secondary outcome measured will include symptom types, severity and duration (recorded by the daily symptom tracker questionnaire), hospital admission and length of stay, oxygen saturation and radiological lung changes on admission, need for ventilatory support (oxygen therapy, CPAP, intubation & ventilation), haematological changes, intensive care admission and length of stay, mortality, subsequent familial/household COVID-19 infection and acquisition of non-COVID-19 upper respiratory tract infections.

Deliverables:

This trial will help us to determine whether carrageenan nasal sprays significantly affect the primary outcome measure of acquisition of COVID-19 infection as confirmed by positive PCR swab taken at the time of symptoms or positive serology measured 2 weeks after symptom onset or at the end of the study.
It will also determine the effect of carrageenan nasal sprays on secondary outcome measures which include types, severity and duration of symptoms, hospital admission and length of stay, need for ventilatory support and intensive care admission, mortality as well as familial or household COVID-19 infection and acquisition of other respiratory tract infections.
We will also investigate whether haematological changes (FBC, CRP, U&E, Ferritin, LFT, LDH, Clotting, D-dimer, FDP, Vitamin D level) and demographic questionnaire findings can offer a predictive value for acquiring COVID-19 infection or determining severity and/or duration of resultant infection.
To determine any associations between symptom severity and/or duration and prognosis in those with COVID-19.
Determine usability and acceptability of nasal and throat spray as prophylaxis and affect on quality adjusted life years and cost effectiveness

Study Design

Study Type:

Interventional

Anticipated Enrollment :

480 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The study design consists of a double blind, randomised placebo-controlled trial. Of the 480 participants recruited, 240 participants will be randomly allocated to each of either the treatment arm (verum Coldamaris plus i.e. Iota-Carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline) or placebo (Coldamaris sine i.e. 0.5% saline) arms.The study design consists of a double blind, randomised placebo-controlled trial. Of the 480 participants recruited, 240 participants will be randomly allocated to each of either the treatment arm (verum Coldamaris plus i.e. Iota-Carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline) or placebo (Coldamaris sine i.e. 0.5% saline) arms.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Allocation to each group, treatment or placebo administration and data analysis will be blinded to both participant and investigator. The sprays will be blinded at the site of manufacture. Trial sealed envelopes will be available in case of any adverse reactions.

Primary Purpose:

Prevention

Official Title:

Efficacy of Carrageenan Nasal and Throat Spray for COVID-19 Prophylaxis - A Double Blind Randomised Placebo-controlled Trial

Actual Study Start Date :

Dec 17, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Coldamaris plus verum Coldamaris plus i.e. 0.12% Iota-Carrageenan plus 0.04% Kappa-Carrageenan in 0.5% saline	Device: Carrageenan nasal and throat spray Iota-carrageenan nasal and throat spray (verum Coldamaris plus i.e. Iota-Carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline)
Placebo Comparator: Coldamaris sine Coldamaris sine i.e. 0.5% saline	Device: Saline nasal and throat spray Saline nasal and throat spray (placebo Coldamaris sine i.e. 0.5% saline)

Arm

Intervention/Treatment

Experimental: Coldamaris plus

verum Coldamaris plus i.e. 0.12% Iota-Carrageenan plus 0.04% Kappa-Carrageenan in 0.5% saline

Device: Carrageenan nasal and throat spray

Iota-carrageenan nasal and throat spray (verum Coldamaris plus i.e. Iota-Carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline)

Placebo Comparator: Coldamaris sine

Coldamaris sine i.e. 0.5% saline

Device: Saline nasal and throat spray

Saline nasal and throat spray (placebo Coldamaris sine i.e. 0.5% saline)

Outcome Measures

Primary Outcome Measures

Rate of COVID-19 infection [9-12 months]
Acquisition of COVID-19 infection as confirmed by positive PCR swab taken at the time of symptom onset or positive serology measured 2 weeks after symptom onset or seroconversion at the end of the trial (via trial entry and exit serology) to detect asymptomatic infection during the study period

Secondary Outcome Measures

Duration of COVID-19 infection [9-12 months]
Time taken for all symptoms to resolve (days)
Hospitalisation due to COVD-19 infection [9-12 months]
Length of hospital and intensive care stay (days)
Severity of COVID-19 infection [9-12 months]
Morality rate
Quality of life of nasal spray use [9-12 months]
Usability of spray and effect on cost and quality adjusted life years

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age ≥18 years;
Study participants who have given informed consent, and received a copy of signed consent form prior to any study related procedures;
Healthcare professionals (nurses, doctors, allied health professionals, health care assistants, operating department practitioners) working in Swansea Bay University Health Board initially as well as any other volunteers >18 years who have not previously tested positive for COVID19 or been vaccinated.
Subjects agree to refrain from taking over the counter products intended to prevent, intervene in, or treat colds/flu, starting at study entry and continuing through week 10 of the study.

Exclusion Criteria:

Capacity, consent and conflicts of interest:

The person lacks capacity;
The subject is related to any study personnel or has any other close ties or conflicts of interest with the research team or the study sponsor;
The subject has received any investigational drug or participated in a clinical trial within 4 weeks of entry to this study.
Unable to complete the daily symptom tracker
Unable to communicate in English or Welsh

Comorbidities:

Known hypersensitivity or allergy to any component of the test product;
Severe cardiovascular, endocrinological, neurological, respiratory, gastrointestinal disease, immune deficiency, autoimmune disease or a history or any current disease that is considered by the investigator as a reason for exclusion;
Severe nasal septal deviation, nasal polyps or other non-infectious condition that could cause nasal obstruction;
A history of any nasal or sinus surgery in the past that in the opinion of the investigator may influence the symptoms or spray administration;
An unrelated infection that in the opinion of the investigator may influence symptoms (gastrointestinal infection, other viral diseases such as measles, mumps);

COVID-19 Status:

Participants with proven COVID-19 infection (previous positive serology and/or viral PCR swab)
Participants that have already received their vaccination or already booked in for their vaccination

Medications:

Recent treatment of common cold that in the opinion of the investigator may influence symptoms (see Table 2)
Participants taking any of the medications outlined in Table 2 during the trial period will be excluded