Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial

Abstract

Objective To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms. Design Pragmatic, double blind, placebo controlled, randomised trial. Setting Eight ear, nose, and throat outpatient clinics, United Kingdom. Participants 346 patients aged 18 years or older with persistent throat symptoms who were randomised according to recruiting centre and baseline severity of symptoms (mild or severe): 172 to lansoprazole and 174 to placebo. Intervention Random blinded allocation (1:1) to either 30 mg lansoprazole twice daily or matched placebo twice daily for 16 weeks. Main outcome measures Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score. Secondary outcomes included symptom response at 12 months, quality of life, and throat appearances. Results Of 1427 patients initially screened for eligibility, 346 were recruited. The mean age of the study sample was 52.2 (SD 13.7) years, 196 (57%) were women, and 162 (47%) had severe symptoms at presentation; these characteristics were balanced across treatment arms. The primary analysis was performed on 220 patients who completed the primary outcome measure within a window of 14-20 weeks. Mean RSI scores were similar between treatment arms at baseline: lansoprazole 22.0 (95% confidence interval 20.4 to 23.6) and placebo 21.7 (20.5 to 23.0). Improvements (reduction in RSI score) were observed in both groups—score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms: estimated difference 1.9 points (95% confidence interval −0.3 to 4.2 points; P=0.096) adjusted for site and baseline symptom severity. Lansoprazole showed no benefits over placebo for any secondary outcome measure, including RSI scores at 12 months: lansoprazole 16.0 (13.6 to 18.4) and placebo 13.6 (11.7 to 15.5): estimated difference 2.4 points (−0.6 to 5.4 points). Conclusions No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up. Trial registration ISRCTN Registry ISRCTN38578686 and EudraCT 2013-004249-17.

AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review

“…34 In addition, PPIs are frequently initiated without a definite indication, notably for empiric treatment of laryngopharyngeal symptoms of cough, throat clearing, globus, and voice hoarseness. Because an RCT has definitively demonstrated that PPIs have no benefit in the empiric management of these symptoms, 35 these patients should be considered for de-prescribing.…”

“…In addition, PPIs at any dose are ineffective in managing laryngopharyngeal symptoms. 35 Highdose PPIs are indicated for Zollinger-Ellison syndrome, which is exceedingly rare (1/1,000,000). 43,44 Therefore, most high-dose PPI users should be considered for stepping down to standard dosing.…”

“…87 A recent RCT also demonstrated that persons who do not have evidence of abnormal esophageal acid exposure (acid exposure time >4.0%) in the first 7 days after PPI withdrawal on ambulatory pH testing are much more likely to not require PPI re-initiation. 35 However, the feasibility of ambulatory pH testing before any attempt at discontinuation is unclear.…”

The Effect of Hyaluronic Acid and Chondroitin Sulphate-Based Medical Device Combined with Acid Suppression in the Treatment of Atypical Symptoms in Gastroesophageal Reflux Disease

“…Although many studies have focused on laryngopharyngeal reflux (LPR), laryngitis, asthma, and chronic cough, their results are inconsistent and only a few are randomized controlled trials (RCTs). The few RCTs that have recently been published suggest that PPIs have little or no superiority to placebo in the treatment of extraesophageal GERD symptoms [ 15 , 16 ].…”

The acid test: Proton pump inhibitors in persistent throat symptoms: A systematic review of systematic reviews

“…Our group recently undertook a rigorous randomised controlled trial (RCT) investigating the role of PPIs in persistent throat symptoms. 6 During our literature reviews, we became concerned about the poor standard of publications, particularly in the systematic review literature. We therefore aimed to critically appraise the literature to determine their scientific validity.…”