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. 2021 Jan;25(3):1–118. doi: 10.3310/hta25030

Lansoprazole for persistent throat symptoms in secondary care: the TOPPITS RCT.

Janet A Wilson, Deborah D Stocken, Gillian C Watson, Tony Fouweather, Julian McGlashan, Kenneth MacKenzie, Paul Carding, Yakubu Karagama, Meredydd Harries, Stephen Ball, Sadie Khwaja, Declan Costello, Ruth Wood, Jan Lecouturier, James O'Hara
PMCID: PMC7869007  PMID: 33492208

Abstract

BACKGROUND

Persistent throat symptoms are commonly attributed to 'laryngopharyngeal reflux'. Despite a limited evidence base, these symptoms are increasingly being treated in primary care with proton pump inhibitors.

OBJECTIVE

To assess the value of proton pump inhibitor therapy in patients with persistent throat symptoms.

DESIGN

This was a double-blind, placebo-controlled, randomised Phase III trial.

SETTING

This was a multicentre UK trial in eight UK ear, nose and throat departments.

PARTICIPANTS

A total of 346 participants aged ≥ 18 years with persistent throat symptoms and a Reflux Symptom Index score of ≥ 10, exclusive of the dyspepsia item, were recruited.

INTERVENTION

Random allocation (1 : 1 ratio) to either 30 mg of lansoprazole twice daily or matched placebo for 16 weeks.

MAIN OUTCOME MEASURE

Symptomatic response (i.e. total Reflux Symptom Index score after 16 weeks of therapy).

RESULTS

A total of 1427 patients were screened and 346 were randomised. The mean age was 52 years (standard deviation 13.7 years, range 20-84 years); 150 (43%) participants were male and 196 (57%) were female; 184 (53%) participants had a mild Reflux Symptom Index minus the heartburn/dyspepsia item and 162 (47%) had a severe Reflux Symptom Index minus the heartburn/dyspepsia item. A total of 172 patients were randomised to lansoprazole and 174 were randomised to placebo.

MAIN OUTCOMES

A total of 267 participants completed the primary end-point visit (lansoprazole, n = 127; placebo, n = 140), of whom 220 did so between 14 and 20 weeks post randomisation ('compliant' group); 102 received lansoprazole and 118 received placebo. The mean Reflux Symptom Index scores at baseline were similar [lansoprazole 22.0 (standard deviation 8.0), placebo 21.7 (standard deviation 7.1), overall 21.9 (standard deviation 7.5)]. The mean Reflux Symptom Index scores at 16 weeks reduced from baseline in both groups [overall 17.4 (standard deviation 9.9), lansoprazole 17.4 (standard deviation 9.9), placebo 15.6 (standard deviation 9.8)]. Lansoprazole participants had estimated Reflux Symptom Index scores at 16 weeks that were 1.9 points higher (worse) than those of placebo participants (95% confidence interval -0.3 to 4.2; padj = 0.096), adjusted for site and baseline severity.

SECONDARY OUTCOMES

Ninety-five (43%) participants achieved a Reflux Symptom Index score in the normal range (< 12) at 16 weeks: 42 (41%) in the lansoprazole group and 53 (45%) in the placebo group. A total of 226 participants completed the end-of-trial follow-up visit (lansoprazole, n = 109; placebo, n = 117), of whom 181 were 'compliant'. The mean Reflux Symptom Index scores at 12 months reduced from baseline in both groups [lansoprazole 16.0 (standard deviation 10.8), placebo 13.6 (standard deviation 9.6), overall 14.7 (standard deviation 10.2)]. A total of 87 (48%) participants achieved a Reflux Symptom Index score in the normal range at 12 months: 33 (40%) in the lansoprazole group and 54 (55%) in the placebo group. Likewise, the Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life total scores and subscales all showed very similar changes in the lansoprazole and placebo cohorts at both 16 weeks and 12 months.

LIMITATIONS

Drop-out rate and compliance are issues in pragmatic clinical trials. The Trial Of Proton Pump Inhibitors in Throat Symptoms (TOPPITS) aimed to detect clinically relevant difference with 90% power. The 346 randomised participants reduced to 283 at the primary end point; 267 completed the primary outcome measure, 220 within the protocol time scale. Despite this, the powers to detect the clinically relevant difference in Reflux Symptom Index score at 16 weeks were 82% (compliant comparison) and 89% (pragmatic comparison). The lack of difference between lansoprazole and placebo is generalisable across NHS clinics.

CONCLUSIONS

Participants on lansoprazole did not report significantly better outcomes than participants on placebo on any of the three patient-reported outcome tools (Reflux Symptom Index, Comprehensive Reflux Symptom Score and Laryngopharyngeal Reflux - Health Related Quality of Life). This multicentre, pragmatic, powered, definitive Phase III trial found no evidence of benefit for patients by treating persistent throat symptoms with lansoprazole.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN38578686 and EudraCT number 2013-004249-17.

FUNDING

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 3. See the NIHR Journals Library website for further project information.

Plain language summary

BACKGROUND

One of the commonest reasons for patients attending hospital throat or voice clinics is persistent throat symptoms, which include a feeling of a lump in the throat, a cough or a hoarse voice. Over time, more of these patients are being treated with proton pump inhibitors to suppress stomach acid in the belief that stomach acid entering the throat causes the symptoms, but there is little evidence that these medications work.

STUDY AIM

The aim of this study is to explore whether or not having a 16-week course of proton pump inhibitors has any impact on throat symptoms. We also tested the usefulness of three different questionnaires in measuring throat symptoms, explored side effects and whether or not patients adhere to treatment, and measured patients’ quality of life.

METHODS

Patients with persistent (lasting for more than 6 weeks) throat symptoms who agreed to participate were randomised to receive either the proton pump inhibitor lansoprazole or a placebo. Participants took lansoprazole or placebo for 16 weeks. Symptoms and quality of life were measured before patients were randomised and at 4 and 12 months after randomisation.

RESULTS

The total number of participants was 346. The mean Reflux Symptom Index outcome score (higher scores meaning worse symptoms) was 22 before the 4-month course of capsules, 16 after 4 months and 15 after 12 months. Participant-reported throat symptoms and quality of life in all participants improved over the 12 months of the study. There was no difference in the symptom improvement experienced by proton pump inhibitor and placebo participants.

CONCLUSIONS

This study shows that proton pump inhibitors do not benefit patients with persistent throat symptoms. Future research should focus on other available therapies.

Full text of this article can be found in Bookshelf.

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