Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study)

BMJ Open. 2017 Jan 16;7(1):e014112. doi: 10.1136/bmjopen-2016-014112.

Abstract

Objectives: 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.

Design: A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough.

Setting: 4 general practitioner (GP) surgeries and 14 pharmacies in the UK.

Participants: 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).

Interventions: 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.

Main outcome measures: 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.

Results: 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.

Conclusions: 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.

Trial registration number: EudraCT number 2014-004255-31.

Keywords: Controlled clinical trial; Cough; Demulcent; Diphenhydramine; Simple Linctus.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Ammonium Chloride / therapeutic use*
  • Antipruritics / therapeutic use
  • Cacao
  • Cough / drug therapy*
  • Demulcents / therapeutic use
  • Diphenhydramine / therapeutic use*
  • Drug Combinations
  • Female
  • Histamine H1 Antagonists / therapeutic use
  • Humans
  • Male
  • Menthol / therapeutic use*
  • Middle Aged
  • Nonprescription Drugs / therapeutic use*
  • Severity of Illness Index
  • Single-Blind Method
  • Treatment Outcome
  • United Kingdom
  • Young Adult

Substances

  • Antipruritics
  • Demulcents
  • Drug Combinations
  • Histamine H1 Antagonists
  • Nonprescription Drugs
  • Ammonium Chloride
  • Menthol
  • Diphenhydramine

Associated data

  • EudraCT/2014-004255-31