Objective: Fludrocortisone is recommended for treatment of neurogenic orthostatic hypotension (nOH) in Parkinson’s disease, but not yet approved by the Food and Drug Administration (FDA). The present study aimed to establish its efficacy compared with that of midodrine, the FDA-approved agent.

Materials and Methods: In these 12-week, open-label, non-inferiority trial, patients aged older than 18 with Parkinson’s disease with nOH defined by a decrease of more than 20 mmHg systolic blood pressure (SBP) or more than 10 mmHg diastolic blood pressure (DBP) when measured in supine and 3-minute upright positions, were randomly assigned (1:1) to receive either fludrocortisone 0.1 mg daily in the morning or midodrine 5 mg twice a day in morning and noon. The primary outcome was the difference of SBP within a 3-minute upright position between the first and 12-week visits. The non-inferiority of fludrocortisone’s efficacy was met if the lower limit of the one-sided 97.5% CI of the mean difference was not beyond -6 mmHg.

Results: Thirty-seven patients were enrolled, 18 with fludrocortisone and 19 with midodrine. Over the period of 12 weeks, the mean increase in SBP within a 3-minute upright position between the groups provided evidence of non-inferiority at 18.11±10.203 mmHg versus 17.36±9.662 mmHg, respectively, with a mean difference 0.74±3.266 (95% CI –5.887 to 7.372, p=0.02) for non-inferiority. The adverse events found more common in the fludrocortisone group were supine hypertension (SH) and hypokalemia.

Conclusion: Fludrocortisone raised SBP within a 3-minute upright position by the same amount as midodrine, despite having more adverse events.