Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial-a study protocol.

INTRODUCTION: Gabapentin is currently used 'off-label' in children and adolescents with chronic neuropathic pain, and reliable evidence of its effects and optimal dosing are lacking.

OBJECTIVES: The GABA-1 trial aims to compare the efficacy and safety of gabapentin liquid formulation relative to tramadol and to explore the pharmacokinetics of both drugs in the treatment of chronic, neuropathic or mixed pain in the paediatric population.

METHODS AND ANALYSIS: The trial is a multicentre, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial. Participants aged from 3 months to <18 years of age with moderate to severe (≥4/10 in age-appropriate pain scales) chronic neuropathic or mixed pain will be recruited in 14 clinical sites in eight European countries. A total of 94 subjects will be randomised to receive gabapentin and tramadol placebo or tramadol and gabapentin placebo throughout 16-19 weeks (including 3 weeks of titration [optimisation period], 12 weeks of treatment at a stable dose [maintenance period] and 1-4 weeks of tapering [discontinuation period]). The primary objective is to assess the efficacy of gabapentin relative to tramadol for the treatment of moderate to severe chronic neuropathic or mixed pain by comparing the difference in average pain scores (assessed by age-appropriate pain scales) between intervention arms after 15 weeks of treatment. Secondary objectives include the assessment of the safety, quality of life and global satisfaction with treatment and the description of the pharmacokinetic-pharmacodynamic relationship of gabapentin liquid formulation and tramadol oral drops to validate the recommended paediatric doses. Only rescue pain medication by paracetamol and/or ibuprofen is allowed during the trial.

ETHICS AND DISSEMINATION: Ethic approval was obtained in the eight participating countries. Results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

TRIAL REGISTRATION NUMBERS: 2014-004851-30 and NCT02722603.

TRIAL STATUS: Ongoing research study, currently recruiting.