title: Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial.
abstract: 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.
  
  
  METHODS
  This 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).
  
  
  RESULTS
  Patients 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.
  
  
  CONCLUSIONS
  The 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.
  
  
  BACKGROUND
  NCT01944631 (clinicaltrials.gov).
authors.affiliation: Common Cold Centre, Cardiff School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: R
authors.initials: R
authors.lastname: Eccles
authors.affiliation: Respiratory Disease Study Center, University of Virginia, Charlottesville, VA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Winther
authors.affiliation: Airway Disease Infection Section & MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Therapeutic Area Virology, Ridgefield, CT, USA.
authors.forename: P
authors.initials: P
authors.lastname: Robinson
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biometrics & Data Management, Ingelheim/Rhein, 55216, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Trampisch
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, CHC Development, Medicine & Regulatory Affairs, Ingelheim/Rhein, 55216, Germany. stephan.koelsch@boehringer-ingelheim.com.
authors.forename: S
authors.initials: S
authors.lastname: Koelsch
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000336:Aerosols; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002351:Carrageenan / Q000008:administration & dosage* / Q000009:adverse effects; D003139:Common Cold / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004770:Enterovirus / Q000187:drug effects / Q000472:pathogenicity; D005260:Female; D006801:Humans; D008297:Male; D012229:Rhinovirus / Q000187:drug effects / Q000472:pathogenicity; D012646:Self Administration; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014852:Wales; D055815:Young Adult
chemical_list: D000336:Aerosols; D000998:Antiviral Agents; D002351:Carrageenan