Association between ramelteon and 30‐day mortality in ICU patients with COVID‐19: A retrospective analysis of the MIMIC‐IV database

Aims Melatonin may improve the prognosis of severe COVID‐19 patients. However, the association between its analogue ramelteon and the survival outcomes of severe COVID‐19 patients remains unclear. This retrospective study was conducted to investigate this knowledge gap. Methods The data of COVID‐19 patients admitted to the ICU were extracted from the Medical Information Mart for Intensive Care IV 3.0 database. Patients were categorized into the ramelteon group and the non‐ramelteon group based on the corresponding treatment. The primary outcome was 30‐day mortality. Subsequently, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were employed to address confounding variables. Kaplan–Meier analysis, Cox proportional hazards regression and subgroup analyses were performed to evaluate the association between ramelteon exposure and survival outcomes. Results This study included 607 unexposed patients and 459 exposed patients. Thirty‐day mortality was 10.2% in the ramelteon group and 30.1% in the non‐ramelteon group. Results from 301 patient pairs in the PSM cohort showed that ramelteon exposure was associated with significantly lower 30‐day mortality (12.3% vs . 19.6%, P = 0.012). IPTW and Cox regression also supported this association ( P < 0.05). Finally, subgroup analysis showed that invasive mechanically ventilated (IMV) patients on ramelteon may have a greater survival benefit ( P interaction = 0.017). Conclusions This study suggests an association between ramelteon exposure and lower 30‐day mortality in ICU patients with COVID‐19, particularly among those receiving IMV. However, given the retrospective design of this study, these findings should be interpreted as hypothesis‐generating rather than definitive.