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

Abstract

ObjectivesTo investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent.DesignA multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough.Setting4 general practitioner (GP) surgeries and 14 pharmacies in the UK.ParticipantsParticipants 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).InterventionsParticipants 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 measuresThe 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.ResultsAt 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.ConclusionsAlthough 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 numberEudraCT number 2014-004255-31.

Methodological considerations in clinical outcomes assessment of pharmacy-based minor ailments management: A systematic review

“…One study utilised an RCT design [ 18 ] and the remainder (n = 18) used observational designs ( Table 3 ). All included studies involved community pharmacy setting for which the clinical outcomes were measured [ 1 , 17 – 34 ].…”

“…All included studies involved community pharmacy setting for which the clinical outcomes were measured [ 1 , 17 – 34 ]. Other settings, such as general practice [ 1 , 18 , 32 ] and EDs [ 1 ], were also included as comparators in measuring effectiveness against pharmacy-based management of minor ailments ( Table 3 ). One study was carried out with pharmacy service users as referred by an out-of-hours telephone helpline for non-life threatening conditions (National Health Service (NHS) Direct) [ 25 ].…”

“…Studies either focused on one therapeutic area such as cough [ 18 , 30 ], cold [ 23 ], skin conditions [ 29 ], gastrointestinal problems [ 22 , 24 , 27 , 32 ] or multiple minor ailment areas [ 1 , 17 , 20 , 21 , 26 , 28 , 33 , 34 ] ( Table 4 ).…”

Tos crónica. Síndrome de hipersensibilidad del reflejo de la tos

“…39 La pérdida del control inhibitorio de la tos distingue también a los pacientes con tos crónica, 40 la cual se ha observado en estudios funcionales al inhalar capsaicina con respuestas de tos. Se ha sugerido que agentes antitusivos centrales como la morfi na 41 y los antihistamínicos de primera generación, como la clorfeniramina y la difenhidramina, 42 actúan a través de su actividad agonista en estas vías inhibitorias centrales. Estos efectos no se relacionan con sedación.…”

“…Medicamentos con efi cacia antitusiva en pacientes con tos inexplicable, tales como opioides (morfi na a través del receptor mu opioide), gabapentina, pregabalina (moduladores de canales de calcio centrales y periféricos), amitriptilina y AF-219 (antagonista de receptores purinéricos P2X3), muestran propiedades neuromoduladoras y también son útiles en el tratamiento del dolor neuropático. 42,47,48,49 El receptor de neurocinina 1 (NK1) ha sido implicado en la sensibilización de sinapsis en el NTS y su antagonista aprepitant ha mostrado reducir la tos en pacientes con cáncer pulmonar.…”