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Neurology. 2014 Jul 22;83(4):328-35. doi: 10.1212/WNL.0000000000000615. Epub 2014 Jun 18.

Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial.

Author information

1
From the Department of Neurology (H.K.), NYU Medical Center, New York; Department of Neurology (R.F.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Medicine (I.B.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (P.L.), Mayo Clinic, Rochester, MN; Chelsea Therapeutics, Inc. (S.P., L.A.H.), Charlotte, NC; Chiltern (J.M.), Wilmington, NC; The Curry Rockefeller Group, LLC (M.F.), Tarrytown, NY; Autonomic and Neurovascular Medicine Departments (C.J.M.), Imperial College London; and Institute of Neurology (C.J.M.), University College London, UK. horacio.kaufmann@nyumc.org.
2
From the Department of Neurology (H.K.), NYU Medical Center, New York; Department of Neurology (R.F.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Medicine (I.B.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (P.L.), Mayo Clinic, Rochester, MN; Chelsea Therapeutics, Inc. (S.P., L.A.H.), Charlotte, NC; Chiltern (J.M.), Wilmington, NC; The Curry Rockefeller Group, LLC (M.F.), Tarrytown, NY; Autonomic and Neurovascular Medicine Departments (C.J.M.), Imperial College London; and Institute of Neurology (C.J.M.), University College London, UK.

Abstract

OBJECTIVE:

To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH).

METHODS:

Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities.

RESULTS:

From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events.

CONCLUSIONS:

In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated.

CLASSIFICATION OF EVIDENCE:

This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days.

PMID:
24944260
PMCID:
PMC4115605
DOI:
10.1212/WNL.0000000000000615
[Indexed for MEDLINE]
Free PMC Article

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