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

H. Albrecht, M. Vernon, G. Solomon

Respiratory Research 2012, 13:118

Purpose:

To compare 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

Methods:

• Randomized, double-blind trial
• 378 participants were enrolled (range 13-85 years); 188 treatment group, 190 placebo group
• Active treatment = two 600 mg extended-release guaifenesin tablets every 12 hours for 7 days
• Efficacy assessed using Daily Cough and Phlegm Diary (DCPD), the Spontaneous Symptom Severity Assessment (SSSA), and the Wisconsin Upper Respiratory Symptom Survey (WURSS)
• End-of-study assessments were completed by patients and investigator
• Validation study Phase 1: patients interviewed to collect evidence to support validity of DCPD, SSSA, and End-of-Treatment assessments
• Validation study Phase 2: examined psychometric properties of assessments

Key Findings:

Convergent validity: correlations between more and less conceptually related measures at Days 1, 4, and 8

Adapted from Albrecht H, et al. Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms. Respir Res 13, 118 (2012).

Validity estimates demonstrated good convergent, discriminant, and known group’s validity, providing evidence of the reliability of SUM8 (8 symptom-related questions) for evaluating changes in URTI symptoms over time with an expectorant treatment.

Results:

Results 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

• As extended-release guaifenesin is an expectorant that improves the rheology and clearance of respiratory tract mucus, this comprehensive measure of phlegm may be optimal for precisely evaluating treatment effects

• Subjective measures of efficacy at Day 4 showed most prominent difference between treatment groups, in favor of guaifenesin, although there were some improvements in earlier time points as well

• SUM8 in the DCPD, which includes three functional items that focus on phlegm and cough analyzed as a composite score, appeared to be the strongest candidate endpoint for further evaluation
• Results from Phase I interviews supported content of assessments which were validated in Phase II
• Treatment was well tolerated, with adverse events reported in 8.5% of patients in the treatment group vs. 5.3% of patients in the placebo group

The CDC notes that OTC medicines “may provide temporary relief of symptoms”¹ for adults and children 6+ years old. This randomized, double-blind trial of 378 participants (aged 13 to 85; 188 treatment, 190 placebo) compared extended-release guaifenesin, an expectorant and the active ingredient in MUCINEX® (two 600 mg tablets every 12 hours for 7 days), with placebo using patient-reported diaries and surveys, followed by a two-phase validation study. The SUM8 diary scores proved robust and reliable as efficacy endpoints for mucoactive drugs, the most prominent difference favoring guaifenesin appeared at Day 4, and treatment was well tolerated (adverse events: 8.5% vs 5.3% with placebo).²

Source:

1 Centers for Disease Control and Prevention. Manage Common Cold. https://www.cdc.gov/common-cold/treatment

2 Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms. https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-13-118