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

• Published in: Health technology assessment (Winchester, England) England), 2021-01, Vol.25 (3), p.1-118
• Main Authors: Wilson, Janet A, Stocken, Deborah D, Watson, Gillian C, Fouweather, Tony, McGlashan, Julian, MacKenzie, Kenneth, Carding, Paul, Karagama, Yakubu, Harries, Meredydd, Ball, Stephen, Khwaja, Sadie, Costello, Declan, Wood, Ruth, Lecouturier, Jan, O'Hara, James
• Format: Article
• Language: English
• Subjects: ear nose and throat; extra oesophageal reflux; laryngopharyngeal reflux; proton pump inhibitor; reflux symptom index
• ISSN: 1366-5278; 2046-4924
• DOI: 10.3310/hta25030

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. To assess the value of proton pump inhibitor therapy in patients with persistent throat symptoms. This was a double-blind, placebo-controlled, randomised Phase III trial. This was a multicentre UK trial in eight UK ear, nose and throat departments. 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. Random allocation (1 : 1 ratio) to either 30 mg of lansoprazole twice daily or matched placebo for 16 weeks. Symptomatic response (i.e. total Reflux Symptom Index score after 16 weeks of therapy). 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. A total of 267 participants completed the primary end-point visit (lansoprazole,  = 127; placebo,  = 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;  = 0.096), adjusted for site and baseline severity. Ninety-five (43%) participants achieved a Reflux Symptom Index score in the normal range (