Amitriptyline for the prevention of post herpetic neuralgia: study protocol for the ATHENA study

Abstract

Background Post herpetic neuralgia (PHN) is the most common complication of herpes zoster, also known as shingles. Amitriptyline has been postulated to prevent PHN. The objective is to determine whether prophylactic low-dose amitriptyline prevents PHN in patients newly diagnosed with shingles. Methods This is a multicentre, individually randomized, pragmatic, placebo-controlled superiority trial with health economic analysis and nested qualitative study. Patients with new-onset shingles are screened by treating clinicians in participating general practitioner surgeries. Key eligibility criteria are age ≥50 years, ≤6 days since rash onset and not already taking (and no contraindication to) amitriptyline. Participants are randomized 1:1 to amitriptyline 10 mg or matched placebo tablets (dose escalated as tolerated to a maximum of three tablets daily for 70 days). Resource-use data (including health, social and informal care, personal expenses and usual activities) are collected from electronic medical records and participant questionnaires. A sample of recruitment conversations are audio-recorded and interviews conducted with recruiters and patients, including those who decline to participate or who withdraw from the trial. Discussion The primary outcome is the presence of PHN (≥3/10 worst pain on Zoster Brief Pain Inventory) at 90 days after rash onset. Primary health economic analyses will present cost per case of PHN prevented and cost per quality-adjusted life year. Qualitative data will be analysed to optimize trial delivery and to aid interpretation and implementation of the trial findings. This is the largest trial to date to evaluate the clinical/cost-effectiveness and acceptability of prophylactic low-dose amitriptyline for the prevention of PHN. Protocol registration. EudraCT 2021-001101-78 and ISRCTN14490832.