Randomised Clinical Trial

Randomised Clinical Trial: The Effects of Pregabalin vs Placebo on Functional Dyspepsia

Isariyaphong Kotikula; Nithi Thinrungroj; Kanokwan Pinyopornpanish; Phuripong Kijdamrongthum; Apinya Leerapun; Taned Chitapanarux; Satawat Thongsawat; Ong-Ard Praisontarangkul

Disclosures

Aliment Pharmacol Ther. 2021;54(8):1026-1032. 

In This Article

Methods

Study Design

This study was a prospective, single-centre, double-blind, randomised controlled trial study conducted at Chiang Mai University Hospital from April 2020 to February 2021. The study was carried out in line with the declaration of Helsinki and Good Clinical Practice guidelines. All patients provided written informed consent before participation in the study. The study was approved by the Institutional Review Board and registered with the Thai Clinical Trials Registry (No. TCTR20200404002).

Participants

All eligible patients were aged 18–70 years, had been diagnosed with FD as defined by Rome IV criteria,[18] and had remained symptomatic after the treatment with a standard dose of PPI for at least 8 weeks before enrolment. All patients had normal upper endoscopy results and no evidence of Helicobacter pylori infection the year prior to enrolment. FD subtypes were determined from a structured interview during the baseline visit.

The exclusion criteria were: (a) had a concurrent diagnosis of gastro-oesophageal reflux disease, irritable bowel syndrome (IBS), or having defaecation problems; (b) had severe comorbid diseases or end-stage renal disease; (c) pregnancy and breastfeeding or planned pregnancy.

Randomisation and Intervention

Computer-generated blocking randomisation was used for patient's randomisation to receive either pregabalin or placebo. An independent staff member assigned the treatments according to consecutive numbers, which were kept in sealed envelopes. All investigators and patients were blinded to treatment allocation. PPIs were held for at least 14 days before the starting of the study medication. Patients allocated to the pregabalin group were prescribed pregabalin 75 mg (Lyrica®, Pfizer inc.) once daily before bedtime for 8 weeks. Patients allocated to the placebo group were given an identical starch-containing capsule to be taken in the same way. During the study, the participants were advised to avoid using over-the-counter medication. An antacid was given as rescue medicine. Compliance was checked by pill count at week 4 and week 8.

Data Collection and Outcome Assessment

Baseline characteristics were documented including age, gender, medical illness, psychiatric condition, FD subtype by Rome IV criteria, the Hospital Anxiety and Depression Scale (HADS),[19,20] FD specific Global Overall Symptom scale and quality of life. The HADS is a well-validated 14 item instrument used to screen for anxiety and depression with 7 anxiety items and 7 depression items yielding a score range of 0–21. Self-reporting of adequate relief, by patient's report of adequate or inadequate relief, was used as the tool to assess patient's satisfaction daily. Patients were considered as a responder if they reported adequate relief over 50% of days during the period of treatment.

Dyspeptic symptom score was assessed using a Global Overall Symptom scale (using the 7-point Likert dyspepsia severity scale) every 4 weeks.[21] The quality of life was assessed using the short-form Nepean Dyspepsia Index[22] at baseline and post-treatment. The authors requested permission to translate the original version into Thai. The translation was done with the forward-backward translation method by the language institute Chiang Mai University and assessed by three independent gastroenterologists for content validity and clarification of the language. The short-form Nepean Dyspepsia Index is divided into 5 subcategories: interference; knowledge/control; eating/drinking; sleep disturbance; work/study and these scores are summarised into the overall quality of life score with a total score of between 10 and 50. Higher scores on the Global Overall Symptom scale and short-form Nepean Dyspepsia Index indicated more severe symptoms and a lower quality of life, respectively.

The primary outcome was an adequate relief response rate. The secondary outcomes were an improvement in the quality of life, overall symptom scores and safety profile.

Statistical Analysis

To date, the placebo response rate in FD is approximately 30%-40% among patients in randomised-controlled trials.[23] Since this was the first trial of pregabalin in the FD study we expect a 30% therapeutic gain over placebo to be clinically significant. The sample size calculation was based on an estimation of 40% responders in the placebo group and 70% responders in the treatment group with a 5% α-error and a 20% β-error. In expectation of a drop-out rate of 20%, the number of participants included in this study needed to be at least 42 patients in each arm. The primary outcome was analysed based on the intention-to-treat analysis. Chi-square test or Fisher's exact test were used to evaluate the difference between the two treatment arms in terms of the proportion of responders, and the rates of adverse events. The dyspepsia symptom score and quality of life scores were compared between the two treatment arms using an independent t-test or Mann-Whitney U test as appropriate. All statistical analyses were performed using Stata (version 16.0 for Windows, StataCorp LCC). A P-value <0.05 was considered a statistically significant difference.

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