Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms

Abstract

BackgroundGuaifenesin is a component of medicines used to improve symptoms associated with upper respiratory tract infections. Patient-reported outcome instruments are valuable for evaluating symptom improvements; however, a validated tool to assess efficacy of mucoactive drugs does not exist. We compared the efficacy of extended-release guaifenesin with placebo for treatment of symptoms of upper respiratory tract infection using subjective efficacy assessments in a pilot study and confirmed precision of assessments in a validation study.MethodsThe pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188) or placebo (n = 190), every 12 hours for 7 days. Efficacy was assessed using subjective measures including the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and the Wisconsin Upper Respiratory Symptom Survey. End-of-study assessments were completed by patients and investigator. The validation study consisted of two phases. In Phase I, subjects completed interviews to gather evidence to support the content validity of the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and Patient’s End-of-Treatment Assessment. Phase II examined the psychometric properties of assessments evaluated in Phase I of the validation study using data from the pilot study.ResultsSubjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin. The 8-symptom related questions (SUM8) in the Daily Cough and Phlegm Diary, analyzed as a composite score appeared to be the strongest candidate endpoint for further evaluation. Results from the interviews in Phase I supported the content of the assessments which were validated during Phase II. Treatments were well tolerated.ConclusionsResults from the clinical pilot and validation studies showed that the SUM8 diary scores were robust and reliable for use as efficacy endpoints in studies of mucoactive drugs.Trial registrationThe study was registered with clinicaltrials.gov (NCT01046136).

Assessment of the Effect of Pharmacotherapy in Common Cold/Acute Bronchitis – the Bronchitis Severity Scale (BSS)

“…Potential benefits of composite outcome scales are their ability to measure clinically relevant changes even in cases where not all of the single endpoints of interest changed or where the endpoints changed to a different extent. Patient-reported outcome instruments are also valuable for evaluating symptom improvements and are used in different areas of respiratory medicine [19], e. g. chronic obstructive pulmonary disease (COPD), asthma research, pulmonary arterial hypertension (PAH), etc. The need for a reliable instrument to estimate disease severity in AB is supported by the efforts of Mwachari and colleagues who employed a multiple item instrument called the Acute Bronchitis Severity Score (ABSS) in 2007 [20,21].…”

Management of respiratory symptoms in paediatric palliative care

“…One paediatric study, however, has shown a benefit of honey preparations over placebo [59]. Adult studies suggest that guaifenesin is an effective protussive [55,58,60].…”

“…Guaifenesin may be an effective protussant [56,60]. Evidence for benefit of honey preparations over placebo, although not studied in palliative care patients [59] Honey preparations should be tried on an individual patient basis, prior to opioids…”

Is Extended-Release Guaifenesin No Better Than a Placebo?

“…8 In the patient-related outcome aspect of this study, extended-release guaifenesin was found to have no effect on all 3 patient-related outcome markers analyzed as measured by the Daily Cough and Phlegm Diary, Spontaneous Symptom Severity Assessment score, and the Wisconsin Upper Respiratory Symptom Survey. 8 Hoffer-Schaefer et al 1 studied 3 physical aspects of sputum, including interfacial tension using a du Noüy ring distraction method, dynamic rheology using a rheometer (AR1500ex, TA Instruments, New Castle, Delaware), and mucus hydration using total sputum weight and percentage hydration. The authors found no difference in any of these 3 sputum properties with guaifenesin compared to a placebo in adolescents and adults with a productive cough secondary to a URTI.…”

“…A more detailed breakdown of the clinical subtype of URTI relating to the study cohort has been reported previously and highlights that 82% of the expectorated sputum samples were from patients with rhinopharyngitis, whereas only 8.5% of the patients had acute bronchitis. 8 One might speculate there is a difference in the pathogenesis, sputum origin, and rheology of expectorated sputum from rhinopharyngitis and acute bronchitis, perhaps suggesting that particular subgroups of RTIs may be more amenable to different classes of expectorants. 9 That said, this medication is marketed as an OTC medication for the subgroup of patients studied in this report.…”