Treating post-menopausal women with symptomatic hand osteoarthritis with hormone replacement therapy (conjugated estrogens and bazedoxifene): primary report from the HOPE-e randomised placebo-controlled feasibility study

Background: Symptomatic hand osteoarthritis (OA) is more common in women and its incidence increases round the age of menopause, implicating estrogen deficiency. No randomised clinical trials (RCTs) of hormone replacement therapy (HRT) have been carried out in hand OA. We set out to determine the feasibility and acceptability of a RCT of a form of HRT (conjugated estrogens-bazedoxifene) in post-menopausal women with painful hand OA. Methods: ISRCTN12196200. Females aged 40-65 years and 1-10 years after final menstrual period with definite hand OA and ≥2 painful hand joints were recruited across three primary/secondary care sites and the community. Design was parallel group, double-blind 1:1 randomisation of conjugated estrogens-bazedoxifene or placebo, orally once daily for 24 weeks, then weaning for 4 weeks before study end. Primary feasibility outcomes were rates of eligible participant identification, recruitment, randomisation, retention, compliance, and likelihood of unblinding. Secondary outcomes generated proof-of-concept quantitative and qualitative data, assessing acceptability of proposed outcomes for a full trial (hand pain/function/appearance, menopause symptoms), and adverse events (AEs), to refine study design. Analysis was intention-to-treat. Progression criteria were pre-defined. Findings: From May2019-Dec2020, 434 enquiries/referrals were received. 33 individuals gave written informed consent to participate. Of the remaining, 250/401 (62%) were ineligible, whilst 55/401 (14%) chose not to proceed. Of 96 telephone pre-screens, 28/35 (80%(95%CI 63%,92%)) eligible participants were randomised. All 28 participants completed all follow-ups with high compliance and outcome measure completeness. All three AE-related treatment withdrawals were on placebo when unblinded. No serious AEs were reported. Participants/investigators were well blinded (participant index 0·50(95%CI 0·25,0·75)). Interpretation: This first ever feasibility study of a RCT of HRT for painful hand OA met its progression criteria, though not powered to detect an effect. This indicates that a full trial of an HRT in this population is feasible and acceptable, identifying possible further design refinements. Funding: Research for Patient Benefit programme, National Institute for Health Researc