TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea-a MASTERMIND study protocol

Abstract

Introduction: Pharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents.

Methods and analysis: TriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA1c) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase-4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA1c after 4 months of therapy (allowing a range of 12-18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects.

Ethical approval: This study was approved by National Health Service Health Research Authority Research Ethics Committee South Central-Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants.

Trial registration numbers: 12039221; 2015-002790-38 and NCT02653209.

Keywords: clinical trials; diabetes & endocrinology; therapeutics.

Conflict of interest statement

Competing interests: EP has received Honoraria from Lilly. NS has consulted for Amgen, Astrazeneca, Boehringer Ingelheim, Eli-Lilly, Napp, NovoNordisk, Sanofi and Pfizer and received grant funding from Boehringer Ingelheim. RRH reports research support from AstraZeneca, Bayer and Merck Sharp & Dohme, and personal fees from Bayer, Intarcia, Merck Sharp & Dohme, Novartis and Novo Nordisk outside the submitted work. CJ has consulted for AstraZeneca, Boehringer Ingelheim, NovoNordisk and Sanofi. WH has received grant funding from IQVIA and travel funds from Eisai.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

TriMaster consort diagram.

Figure 2

TriMaster schedule of assessment. 1Where baseline visit takes place more than 2 weeks after screening visit, eligibility blood samples must be repeated. 2Optional procedure for participants at sites which have previously agreed to sample collection. 3Analysis performed on both visit 1 baseline and visit 1 mixed-meal tolerance test samples. Other analyses at visit 1 performed on baseline only. DTSQ, Diabetes Treatment Satisfaction Questionnaire; HbA1c, glycated haemoglobin; IMP, investigational medicinal product