Efficacy and Safety of Oral Micronized Progesterone That Converts to Allopregnanolone as an Adjunctive Treatment in Refractory Status Epilepticus: A Prospective Interventional Phase IIa Study

Background: We aimed to study the efficacy and safety of allopregnanolone which convert from oral micronized progesterone as an adjunctive treatment for Thai patients with refractory status epilepticus.Methods: Adults 18–80 years old who diagnosed with either convulsive or non-convulsive refractory status epilepticus receiving standard AED treatment, intravenous midazolam, for longer than 60 minutes were included. The intervention group received Utrogestran® (micronized progesterone, 200 mg/capsule) via enteric feeding every 8 h for five days. Treatments for RSE were continuing along the clinical trial period. Serum allopregnanolone levels were measured by radioimmunoassay (DetectX® Allopregnanolone Immunoassay Kit; Arbor Assays, Michigan, United States). Control patients were randomly selected from our hospital RSE cohort during 2015–2019. Continuous data were presented as the mean and standard deviation. Discrete data were assessed by number and percentage. The changes in laboratories were analyzed by paired t-test. The difference between groups were compared by independent sample t-test. The Mann-Whitney U test, Chi-square test or Fisher’s exact test were used for non-parametric parameters. A p-value < 0.05 indicated statistical significance. All analyses were performed using SPSS version 26 software (IBM Corp., Armonk, NY).Results: The average duration of refractory status epilepticus after treatment with midazolam plus progesterone (intervention group) and without progesterone until status epilepticus termination was 25.5 and 58.4 hours, (p = 0.004), indicated that allopregnanolone significantly shortens the refractory status epilepticus duration in vivo.Conclusions: Allopregnanolone, produced from oral micronized progesterone, demonstrates efficacy and safety in treating refractory status epilepticus as an adjunctive treatment.Trial registration: This trial was registered in Thai Clinical Trials Registry (TCTR) database. The trial registration number was “TCTR20200717002”, 16 July 2020, retrospectively registered.