Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury.

OBJECTIVES

To determine the effect of an escalating dose of droxidopa (100, 200, and 400 mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effect of droxidopa on (1) supine BP and heart rate, (2) the change in BP and heart rate when these individuals were transferred from the supine to the seated position, and (3) adverse event (AE) reporting.

DESIGN

Open-label dose titration trial.

SETTING

A Veterans Administration Medical Center.

PARTICIPANTS

Participants with SCI (C3-T12) (N=10) were studied during 4 laboratory visits. Subjects visited the laboratory for about 5 hours on each visit, which incorporated a 30-minute seated baseline, a 30- to 60-minute supine, and a 4-hour seated postdrug observation.

INTERVENTIONS: Placebo on visit 1, droxidopa 100 mg on visit 2, droxidopa 200 mg on visit 3, and droxidopa 400 mg on visit 4.

MAIN OUTCOME MEASURES: BP and heart rate changes from baseline to the postdrug period, orthostatic heart rate and BP responses, and subjective AE reporting.

RESULTS

Seated BP was significantly elevated with 400 mg droxidopa compared with placebo and 100 mg droxidopa for 3 hours and was elevated for 2 hours compared with 200 mg droxidopa. Increase in supine BP was not worsened following droxidopa, and the expected fall in BP when transferred to the seated position was prevented with droxidopa 200 and 400 mg. There were no significant differences in the heart rate response or AE reporting among the study visits.

CONCLUSIONS

Our preliminary findings suggest that droxidopa, at the doses tested, does not cause excessive increases in supine BP and the 400-mg dose appears to be effective at increasing seated BP for up to 3 hours in persons with SCI.