title: Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study).
abstract: To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent.
  
  
  
  A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough.
  
  
  
  4 general practitioner (GP) surgeries and 14 pharmacies in the UK.
  
  
  
  Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0-100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females).
  
  
  
  Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough.
  
  
  
  The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed.
  
  
  
  At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was -5.9 mm (-14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was -4.2 mm (-12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference -11.6 mm (-20.6 to 2.7), p=0.01) and cough frequency (mean difference -8.1 mm (-16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely stopped treatment due to cough improvement in the CS1002 group (24.4%) compared with SL (10.7%; p=0.02). Adverse events (AEs) were comparable between CS1002 (20.5%) and SL (27.6%) and largely related to the study indication. 6 participants (7%) in the CS1002 group reduced the dose of medication due to drowsiness/tiredness, which subsequently resolved. These events were not reported by participants as AEs.
  
  
  
  Although the primary end point was not achieved, CS1002 was associated with greater reductions in cough frequency, sleep disruption and improved health status compared with SL.
  
  
  
  EudraCT number 2014-004255-31.
authors.affiliation: Division of Asthma, Allergy and Lung Biology, King's College London, London, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: Birring
authors.affiliation: Infirst Healthcare Ltd, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Brew
authors.affiliation: Infirst Healthcare Ltd, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kilbourn
authors.affiliation: Infirst Healthcare Ltd, London, UK.
authors.forename: V
authors.initials: V
authors.lastname: Edwards
authors.affiliation: Spica Consultants Ltd, Marlborough, UK.
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.affiliation: Hull York Medical School, Castle Hill Hospital, East Yorkshire, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Morice
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000643:Ammonium Chloride / Q000627:therapeutic use*; D000982:Antipruritics / Q000627:therapeutic use; D002099:Cacao; D003371:Cough / Q000188:drug therapy*; D065106:Demulcents / Q000627:therapeutic use; D004155:Diphenhydramine / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008610:Menthol / Q000627:therapeutic use*; D008875:Middle Aged; D004366:Nonprescription Drugs / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016896:Treatment Outcome; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000982:Antipruritics; D065106:Demulcents; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; D004366:Nonprescription Drugs; D000643:Ammonium Chloride; D008610:Menthol; D004155:Diphenhydramine
keywords: Controlled clinical trial; Cough; Demulcent; Diphenhydramine; Simple Linctus