Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials

Koenighofer, Martin; Lion, Thomas; Bodenteich, Angelika; Prieschl-Grassauer, Eva; Grassauer, Andreas; Unger, Hermann; Mueller, Christian A.; Fazekas, Tamás

doi:10.1186/2049-6958-9-57

Cited by 85 publications

(113 citation statements)

References 22 publications

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“…Consistent trends in favor of I-C for secondary endpoints and statistically significant outcomes for exploratory analyses were also observed for the ICICC trial. The finding that nominally greater treatment effects were seen in the ICICC trial among patients who were viruspositive, is supported by a pooled analysis by Koenighofer [14], which combined the Fazekas and Ludwig trials [6,7]. The pooled analysis examined only those patients who were virus-positive, and showed that nominal response rates were higher in virus-positive patients than in all participants of the Ludwig and Fazekas trials.…”

Section: Discussionmentioning

confidence: 91%

Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial

et al. 2015

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Iota-carrageenan (I-C) is active against respiratory viruses in vitro and was effective as nasal spray in three previous clinical trials. The current trial served to further investigate I-C in patients with early common cold symptoms.MethodsThis randomized, placebo-controlled, double-blind phase IV trial was conducted in 200 adult patients with self-diagnosed colds of <48 h’ duration that were confirmed by baseline cold symptom scores. Patients were to self-administer 0.12 % I-C or placebo spray (NaCl 0.5 %) four times daily for four to ten days and record symptom information for ten days. Common respiratory viruses were quantified by RT-PCR during pretreatment and on Day 3 or 4. The primary endpoint was the mean total symptom score (TSS) of eight cold symptoms on Days 2–4 (TSS2–4).ResultsPatients in both treatment groups had similar baseline TSSs (mean TSS: 6.75 for I-C and 6.79 for placebo). Viruses were detected in baseline samples from 53 of 98 I-C patients (54.1 %) and 54 of 97 placebo patients (55.7 %). Mean ± SE for TSS2–4 was 5.78 ± 0.25 for I-C patients and 6.39 ± 0.25 for placebo (p = 0.0895). Exploratory analyses after unblinding (TSS2–4 excluding a patient with aberrantly high symptom scores [TSS2–4, ex 1pt]; mean of TSS over Days 1–4 [TSS1–4]; change in TSS1–4 relative to baseline [TSS1–4, rel]) demonstrated treatment differences in favor of I-C (p = 0.0364, p = 0.0495 and p = 0.0421, respectively). For patients with quantifiable rhinovirus/enterovirus at baseline, there was a trend towards greater reduction of virus load at Day 3 or 4 (p = 0.0958; I-C: 90.2 % reduction in viral load; placebo: 72.0 %). Treatments were well tolerated with no differences in adverse event rates.ConclusionsThe primary endpoint did not demonstrate a statistically significant difference between I-C and placebo but showed a trend towards I-C benefit. Exploratory analyses indicated significant reduction of cold symptoms in the I-C group relative to placebo during the first four days when symptoms were most severe, and also substantiated I-C’s activity against rhinovirus/enterovirus.Trial registrationNCT01944631 (clinicaltrials.gov)

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Section: Discussionmentioning

confidence: 91%

Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial

et al. 2015

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“…Carrageenan has been extensively used in food, cosmetic and pharmaceutical industries, and is on the FDA's list of generally recognized as safe (GRAS) products for consumption (21 CFR 172.620). We demonstrated the antiviral effectiveness of iota-carrageenan against a variety of respiratory viruses in several preclinical and clinical trials; [21][22][23][24][25][26] therefore, it has been approved for marketing in the EU, Asia and Australia as part of a variety of over-the-counter products addressing common cold and related diseases.…”

Section: Discussionmentioning

confidence: 97%

“…[23][24][25] The pooled analysis of two studies conducted in 153 children and 203 adults revealed that patients infected with any respiratory virus who were intranasally treated with iota-carrageenan showed a 1.9-day faster recovery from common cold symptoms than placebo-treated patients in the intention-to-treat population. 26 Carrageenan is contained in medical device nasal sprays that have been approved and marketed in the EU for 10 years for the supportive treatment of common cold/flu-like illnesses caused by viruses.…”

Section: Introductionmentioning

confidence: 99%

Development of a nasal spray containing xylometazoline hydrochloride and iota-carrageenan for the symptomatic relief of nasal congestion caused by rhinitis and sinusitis

Gräf¹,

Bernkop‐Schnürch²,

Egyed³

et al. 2018

IJGM

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IntroductionXylometazoline hydrochloride (HCl) is a nasal decongestant that causes vasoconstriction in the nasal submucosa. It has been used for more than 50 years for the treatment of nasal congestion caused by rhinitis/sinusitis. Iota-carrageenan is effective against a broad variety of respiratory viruses, which are the most common cause of infections of the upper respiratory tract. Therefore, it is used as the active component in the antiviral nasal spray Coldamaris prophylactic (1.2 mg/mL iota-carrageenan in 0.5% NaCl) and other medical device nasal sprays that are approved and marketed in the EU. Recently, we developed a nasal spray formulation containing both xylometazoline HCl (0.05%) and iota-carrageenan (0.12%) that provides decongestion and antiviral protection of the nasal mucosa at the same time.ResultsA set of in vitro experiments revealed that the vasoconstrictive properties of xylometazoline HCl and the antiviral effectiveness of iota-carrageenan against human rhinovirus (hRV) 1a, hRV8 and human coronavirus OC43 were maintained in the formulation containing these two compounds. Permeation experiments using bovine nasal mucosa showed that iota-carrageenan had no significant influence on the permeation of xylometazoline HCl. Finally, in the local tolerance and toxicity study, it was shown that the formulation was well tolerated at the application site with no occurrence of erythema or edema in the nostrils of all rabbits or any signs of toxicity in any of the organs and tissues inspected.ConclusionInvestigations on compatibility of xylometazoline HCl and iota-carrageenan demonstrated that the substances do not influence each other, allowing both to fulfill their known specific clinical efficacy (xylometazoline HCl) and effectiveness (iota-carrageenan).

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“…We published that iota-carrageenan is a potent inhibitor of hRV [36] and influenza A [37] replication and demonstrated the antiviral efficacy of iota-carrageenan against common cold viruses by intranasal application in several randomized, double-blind, parallel group, placebo-controlled clinical trials [38][39][40]. The pooled analysis of two studies conducted in 153 children and 203 adults revealed that patients infected with any respiratory virus, who were intranasally treated with iota-carrageenan showed a 1.9 day faster recovery from common cold symptoms than placebo treated patients in the intention-to-treat population [41,42]. The anti-influenza activity was shown by subgroup analysis of 49 influenza infected patients who benefited from a 3.3 days faster recovery from symptoms.…”

Section: Introductionmentioning

confidence: 97%

The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model

et al. 2015

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BackgroundCarrageenan is a clinically proven and marketed compound for the treatment of viral upper respiratory tract infections. As infections caused by influenza virus are often accompanied by infections with other respiratory viruses the combination of a specific anti-influenza compound with the broadly active antiviral polymer has huge potential for the treatment of respiratory infections. Thus, the combination of the specific anti-influenza drug Zanamivir together with carrageenan in a formulation suitable for intranasal application was evaluated in-vitro and in-vivo.Principal FindingsWe show in-vitro that carrageenan and Zanamivir act synergistically against several influenza A virus strains (H1N1(09)pdm, H3N2, H5N1, H7N7). Moreover, we demonstrate in a lethal influenza model with a low pathogenic H7N7 virus (HA closely related to the avian influenza A(H7N9) virus) and a H1N1(09)pdm influenza virus in C57BL/6 mice that the combined use of both compounds significantly increases survival of infected animals in comparison with both mono-therapies or placebo. Remarkably, this benefit is maintained even when the treatment starts up to 72 hours post infection.ConclusionA nasal spray containing carrageenan and Zanamivir should therefore be tested for prevention and treatment of uncomplicated influenza in clinical trials.

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Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials

Cited by 85 publications

References 22 publications

Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial

Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial

Development of a nasal spray containing xylometazoline hydrochloride and iota-carrageenan for the symptomatic relief of nasal congestion caused by rhinitis and sinusitis

The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model

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