Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa

Italo Biaggioni, Roy Freeman, Christopher J. Mathias, Phillip Low, L. Arthur Hewitt, Horacio Kaufmann

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

We evaluated whether droxidopa, a prodrug converted to norepinephrine, is beneficial in the treatment of symptomatic neurogenic orthostatic hypotension, which results from failure to generate an appropriate norepinephrine response to postural challenge. Patients with symptomatic neurogenic orthostatic hypotension and Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa titration (100-600 mg, 3× daily). Responders then received an additional 7-day open-label treatment at their individualized dose. Patients were subsequently randomized to continue with droxidopa or withdraw to placebo for 14 days. We then assessed patient-reported scores on the Orthostatic Hypotension Questionnaire and blood pressure measurements. Mean worsening of Orthostatic Hypotension Questionnaire dizziness/lightheadedness score from randomization to end of study (the primary outcome; N=101) was 1.9±3.2 with placebo and 1.3±2.8 units with droxidopa (P=0.509). Four of the other 5 Orthostatic Hypotension Questionnaire symptom scores and all 4 symptom-impact scores favored droxidopa, with statistical significance for the patient's self-reported ability to perform activities requiring standing a short time (P=0.033) and standing a long time (P=0.028). Furthermore, a post hoc analysis of a predefined composite score of all symptoms (Orthostatic Hypotension Questionnaire composite) demonstrated a significant benefit for droxidopa (P=0.013). There was no significant difference between groups for standing systolic blood pressure (P=0.680). Droxidopa was well tolerated. In summary, this randomized withdrawal droxidopa study failed to meet its primary efficacy end point. Additional clinical trials are needed to confirm that droxidopa is beneficial in symptomatic neurogenic orthostatic hypotension, as suggested by the positive secondary outcomes of this trial.

Original languageEnglish (US)
Pages (from-to)101-107
Number of pages7
JournalHypertension
Volume65
Issue number1
DOIs
StatePublished - Jan 20 2015

Keywords

  • Autonomic Nervous System
  • Droxidopa
  • Multiple System Atrophy
  • Norepinephrine
  • Parkinson Disease

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa'. Together they form a unique fingerprint.

  • Cite this