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

Abstract

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.