title: Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial.
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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Horacio
authors.initials: H
authors.lastname: Kaufmann
authors.affiliation: 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.
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
authors.affiliation: 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.
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.affiliation: 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.
authors.forename: Phillip
authors.initials: P
authors.lastname: Low
authors.affiliation: 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.
authors.forename: Simon
authors.initials: S
authors.lastname: Pedder
authors.affiliation: 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.
authors.forename: L Arthur
authors.initials: LA
authors.lastname: Hewitt
authors.affiliation: 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.
authors.forename: Joe
authors.initials: J
authors.lastname: Mauney
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Feirtag
authors.affiliation: 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.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Mathias
mesh_terms: D000368:Aged; D001337:Autonomic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D004244:Dizziness / Q000188:drug therapy; D004311:Double-Blind Method; D015103:Droxidopa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000150:complications / Q000188:drug therapy; D009422:Nervous System Diseases / Q000150:complications* / Q000188:drug therapy; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy; D011187:Posture; D054970:Pure Autonomic Failure / Q000150:complications / Q000188:drug therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001337:Autonomic Agents; D015103:Droxidopa