Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial

Martin Ludwig, Elisabeth Enzenhofer, Sven Schneider, Margit Rauch, Angelika Bodenteich, Kurt Neumann, Eva Prieschl-Grassauer, Andreas Grassauer, Thomas Lion, Christian A Mueller, Martin Ludwig, Elisabeth Enzenhofer, Sven Schneider, Margit Rauch, Angelika Bodenteich, Kurt Neumann, Eva Prieschl-Grassauer, Andreas Grassauer, Thomas Lion, Christian A Mueller

Abstract

Background: The common cold is the most widespread viral infection in humans. Iota-carrageenan has previously shown antiviral effectiveness against cold viruses in clinical trials. This study investigated the efficacy of a carrageenan-containing nasal spray on the duration of the common cold and nasal fluid viral load in adult patients.

Methods: In a randomized, double-blind, placebo-controlled trial, 211 patients suffering from early symptoms of the common cold were treated for seven days. Application was performed three times daily with either a carrageenan-supplemented nasal spray or saline solution as placebo with an overall observation period of 21 days. The primary endpoint was the duration of disease defined as the time until the last day with symptoms followed by all other days in the study period without symptoms. During the study, but prior unblinding, the definition of disease duration was adapted from the original protocol that defines disease duration as the time period of symptoms followed by 48 hours without symptoms.

Results: In patients showing a laboratory-confirmed cold virus infection and adherence to the protocol, alleviation of symptoms was 2.1 days faster in the carrageenan group in comparison to placebo (p = 0.037). The primary endpoint that had been prespecified but was changed before unblinding was not met. Viral titers in nasal fluids showed a significantly greater decrease in carrageenan patients in the intention-to-treat population (p = 0.024) and in the per protocol population (p = 0.018) between days 1 and 3/4.

Conclusions: In adults with common cold virus infections, direct local administration of carrageenan with nasal sprays reduced the duration of cold symptoms. A significant reduction of viral load in the nasal wash fluids of patients confirmed similar findings from earlier trials in children and adults.

Trial registration: Current Controlled Trials ISRCTN80148028.

Figures

Figure 1
Figure 1
COP 03/09 trial, patient flow chart.
Figure 2
Figure 2
Alleviation of symptoms in patients infected with a cold virus treated either with intranasal Carrageenan or placebo. Alleviation was defined as the time until complete absence of cold symptoms followed by all other days in the study period without cold symptoms. Figure 2A shows the ITT-VP population p = 0.077 and Figure 2B shows the PP-VP population p = 0.037.
Figure 3
Figure 3
Mean daily rate of TSS reduction in the second phase of the cold. The mean daily rate of TSS reduction was calculated from the variable a2 that was determined by ReWuMod analysis and is shown for the ITT-VP (3A), p = 0.029 and PP-VP populations (3B) p = 0.048. Details describing the ReWuMod analysis are shown in supplementary Figure 1.
Figure 4
Figure 4
Differences in viral load between days 1 and 3/4. The median log10 difference of the viral load between days 1 and days 3 or 4 determined with quantitative real time PCR for a set of respiratory viruses as described in the materials and methods is shown. The titers were compared by applying a Median-test. A: ITT-VP p = 0.024; B: PP-VP: p = 0.018. The black bar shows Iota-Carrageenan and the grey bar shows placebo.

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