A pilot study on the melatonin treatment in patients with early septic shock: results of a single-center randomized controlled trial

BACKGROUND: We assessed the potential impact of a high dose of melatonin treatment in patients with early septic shock. METHODS: Forty patients with early septic shock were randomly allocated to the melatonin or placebo groups. Besides standard-of-care treatment, melatonin and placebo were administered at a dose of 50 mg for five consecutive nights. The efficacy outcomes were severity of organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score, the number of patients requiring mechanical ventilation and ventilator-free days, the mean required vasopressor dose and vasopressor-free days, and 28 days all-cause mortality. RESULTS: After 5-day treatment, the mean SOFA scores decreased 4.05 ± 4.75 score in the melatonin group and 2.25 ± 4.87 in the placebo group. On day 28, 60% of the melatonin-treated patients and 35% of the placebo-treated patients had a SOFA score below six. Thirteen cases in the placebo group and nine cases in the melatonin group required mechanical ventilation; however, there was no statistically significant difference between the groups regarding these outcomes. The melatonin-treated patients had more ventilator-free days than placebo-treated patients over the 28-day (16.90 ± 9.24 vs. 10.00 ± 10.94; p value = 0.035). The mean reduction in the required dose of vasopressor was 6.2 ± 5.12 in the melatonin-treated patients compared to 3.20 ± 3.95 in the placebo-treated patients (p value = 0.045). Vasopressor-free days in the melatonin-treated group were also significantly more than the placebo-treated group (12.75 ± 7.43 days vs. 10.15 ± 6.12 days; p value = 0.046). CONCLUSIONS: Our pilot study supported the potential benefits of melatonin in treating septic shock. Further clinical evidence is required for expanding and confirming these findings. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (ID code: IRCT20120215009014N296). Registration date: 15/09/2019.