Carrageenan Nasal Spray for COVID-19 Prophylaxis (ICE-COVID)
Primary Purpose
COVID-19, SARS-CoV 2
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Carrageenan nasal and throat spray
Saline nasal and throat spray
Sponsored by
About this trial
This is an interventional prevention trial for COVID-19 focused on measuring Carrageenan, Nasal spray, Anti-viral, Prevention, Carragelose
Eligibility Criteria
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
Sites / Locations
- Joint Clinical Research Facility
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Coldamaris plus
Coldamaris sine
Arm Description
verum Coldamaris plus i.e. 0.12% Iota-Carrageenan plus 0.04% Kappa-Carrageenan in 0.5% saline
Coldamaris sine i.e. 0.5% saline
Outcomes
Primary Outcome Measures
Rate of COVID-19 infection
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
Time taken for all symptoms to resolve (days)
Hospitalisation due to COVD-19 infection
Length of hospital and intensive care stay (days)
Severity of COVID-19 infection
Morality rate
Quality of life of nasal spray use
Usability of spray and effect on cost and quality adjusted life years
Full Information
NCT ID
NCT04590365
First Posted
May 28, 2020
Last Updated
April 27, 2023
Sponsor
Swansea University
Collaborators
Cardiff University, Marinomed Biotech AG, Walgreens Boots Alliance, Abertawe Bro Morgannwg University Health Board
1. Study Identification
Unique Protocol Identification Number
NCT04590365
Brief Title
Carrageenan Nasal Spray for COVID-19 Prophylaxis
Acronym
ICE-COVID
Official Title
Efficacy of Carrageenan Nasal and Throat Spray for COVID-19 Prophylaxis - A Double Blind Randomised Placebo-controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
December 17, 2020 (Actual)
Primary Completion Date
November 18, 2022 (Actual)
Study Completion Date
November 18, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swansea University
Collaborators
Cardiff University, Marinomed Biotech AG, Walgreens Boots Alliance, Abertawe Bro Morgannwg University Health Board
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, SARS-CoV 2
Keywords
Carrageenan, Nasal spray, Anti-viral, Prevention, Carragelose
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
480 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Coldamaris plus
Arm Type
Experimental
Arm Description
verum Coldamaris plus i.e. 0.12% Iota-Carrageenan plus 0.04% Kappa-Carrageenan in 0.5% saline
Arm Title
Coldamaris sine
Arm Type
Placebo Comparator
Arm Description
Coldamaris sine i.e. 0.5% saline
Intervention Type
Device
Intervention Name(s)
Carrageenan nasal and throat spray
Intervention Description
Iota-carrageenan nasal and throat spray (verum Coldamaris plus i.e. Iota-Carrageenan 0.12% plus 0.04% Kappa-Carrageenan in 0.5% saline)
Intervention Type
Device
Intervention Name(s)
Saline nasal and throat spray
Intervention Description
Saline nasal and throat spray (placebo Coldamaris sine i.e. 0.5% saline)
Primary Outcome Measure Information:
Title
Rate of COVID-19 infection
Description
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
Time Frame
9-12 months
Secondary Outcome Measure Information:
Title
Duration of COVID-19 infection
Description
Time taken for all symptoms to resolve (days)
Time Frame
9-12 months
Title
Hospitalisation due to COVD-19 infection
Description
Length of hospital and intensive care stay (days)
Time Frame
9-12 months
Title
Severity of COVID-19 infection
Description
Morality rate
Time Frame
9-12 months
Title
Quality of life of nasal spray use
Description
Usability of spray and effect on cost and quality adjusted life years
Time Frame
9-12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zita M Jessop, MBBChir PhD
Organizational Affiliation
Swansea University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Joint Clinical Research Facility
City
Swansea
ZIP/Postal Code
SA6 6NL
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
16839203
Citation
Buck CB, Thompson CD, Roberts JN, Muller M, Lowy DR, Schiller JT. Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog. 2006 Jul;2(7):e69. doi: 10.1371/journal.ppat.0020069.
Results Reference
background
PubMed Identifier
20696083
Citation
Eccles R, Meier C, Jawad M, Weinmullner R, Grassauer A, Prieschl-Grassauer E. Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold. Respir Res. 2010 Aug 10;11(1):108. doi: 10.1186/1465-9921-11-108.
Results Reference
background
PubMed Identifier
26438038
Citation
Eccles R, Winther B, Johnston SL, Robinson P, Trampisch M, Koelsch S. Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial. Respir Res. 2015 Oct 5;16:121. doi: 10.1186/s12931-015-0281-8.
Results Reference
background
PubMed Identifier
2823697
Citation
Gonzalez ME, Alarcon B, Carrasco L. Polysaccharides as antiviral agents: antiviral activity of carrageenan. Antimicrob Agents Chemother. 1987 Sep;31(9):1388-93. doi: 10.1128/AAC.31.9.1388.
Results Reference
background
PubMed Identifier
18817582
Citation
Grassauer A, Weinmuellner R, Meier C, Pretsch A, Prieschl-Grassauer E, Unger H. Iota-Carrageenan is a potent inhibitor of rhinovirus infection. Virol J. 2008 Sep 26;5:107. doi: 10.1186/1743-422X-5-107.
Results Reference
background
PubMed Identifier
24219370
Citation
Ludwig M, Enzenhofer E, Schneider S, Rauch M, Bodenteich A, Neumann K, Prieschl-Grassauer E, Grassauer A, Lion T, Mueller CA. Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial. Respir Res. 2013 Nov 13;14(1):124. doi: 10.1186/1465-9921-14-124.
Results Reference
background
PubMed Identifier
21179403
Citation
Leibbrandt A, Meier C, Konig-Schuster M, Weinmullner R, Kalthoff D, Pflugfelder B, Graf P, Frank-Gehrke B, Beer M, Fazekas T, Unger H, Prieschl-Grassauer E, Grassauer A. Iota-carrageenan is a potent inhibitor of influenza A virus infection. PLoS One. 2010 Dec 14;5(12):e14320. doi: 10.1371/journal.pone.0014320.
Results Reference
background
PubMed Identifier
25969984
Citation
Shao Q, Guo Q, Xu Wp, Li Z, Zhao Tt. Specific Inhibitory Effect of kappa-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus. PLoS One. 2015 May 13;10(5):e0126577. doi: 10.1371/journal.pone.0126577. eCollection 2015.
Results Reference
background
PubMed Identifier
36109791
Citation
Jessop ZM, Gibson J, Lim JY, Jovic TH, Combellack E, Dobbs TD, Carter K, Hiles S, Islam S, Healy B, Humphreys I, Eccles R, Hutchings HA, Whitaker IS. 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. Trials. 2022 Sep 15;23(1):782. doi: 10.1186/s13063-022-06685-z.
Results Reference
derived
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Carrageenan Nasal Spray for COVID-19 Prophylaxis
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