Melatonin to improve sleep in patients undergoing major surgery: protocol for a double-blind, randomised...

Sleep disturbance is common after major surgery and may impair recovery, immune function and postoperative outcomes. Environmental disruptions, pain and routine hospital care often contribute to poor sleep during hospitalisation. Sedative medications such as benzodiazepines are frequently used but may cause adverse effects. Melatonin, a hormone regulating circadian rhythm, has been shown to improve sleep disturbance with a favourable safety profile; however, evidence for its perioperative use remains limited.

The MELROSE trial is a prospective, double-blind, randomised placebo-controlled trial conducted at John Hunter Hospital. Adults undergoing elective major abdominal or orthopaedic surgery with an expected hospital stay of more than 48 hours are randomised 1:1 to receive melatonin (5 mg sublingual wafer) or placebo. Study medication is administered the night before surgery and nightly postoperatively at 21:00 hours for up to 7 days or until discharge. The primary outcome is the raw Patient-Reported Outcome Measurement Information System (PROMIS) Sleep Disturbance 8a score on postoperative day 3. Secondary outcomes include serum cortisol levels, postoperative complications (Clavien-Dindo classification), length of stay, delirium incidence, 30-day mortality and quality of life with the EuroQuol 5 Dimension 5 levels quality of life scale(EQ-5D-5L). The study aims to recruit 340 participants, with 170 participants per treatment group. The primary analysis will compare treatment groups using an Analysis of Covariance (ANCOVA) model adjusted for baseline PROMIS score and randomisation strata.

This study has been approved by the Hunter New England Human Research Ethics Committee (2019/ETH13791) protocol V11_ 22 January 2026. Study findings will be presented at local and national conferences and in scientific research journals.

ACTRN12620000031965.