Evidence map›Paper›PMID 24944260›Full record

Trial reportNeurology2014

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

Horacio Kaufmann, Roy Freeman, Italo Biaggioni, Phillip Low, Simon Pedder, L Arthur Hewitt, Joe Mauney, Michael Feirtag, Christopher J Mathias, NOH301 Investigators

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 114 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 6 pooled it
29.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03446807 phase2withdrawnnot on this mapstarted 2021, after this paper: background citation

Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism

TypeinterventionalSponsorLoma Linda UniversityRan2021 to 2023Enrolled0ConditionsParkinson Disease, Multiple System Atrophy, Progressive Supranuclear PalsyArmsDroxidopa, Placebo Oral Tablet
NCT03602014 phase4completednot on this mapstarted 2018, after this paper: background citation

Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury

TypeinterventionalSponsorJames J. Peters Veterans Affairs Medical CenterRan2018 to 2021Enrolled22ConditionsHypotension, Orthostatic, Hypotension, Spinal Cord InjuriesArmsNorthera, Placebo
3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 6 syntheses or guidelines pooled it, 273 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Guideline
  4. Pooled it
  5. Pooled it
  6. Meta-analysis of the safety and efficacy of droxidopa for neurogenic orthostatic hypotension.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2016
    Pooled it
  7. Trial
  8. Establishing minimally clinically important differences for the orthostatic hypotension questionnaire (OHQ).Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026
    Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Review
  16. The Noradrenergic Brain in Parkinson's Disease.Current neurology and neuroscience reports · 2026
    Review
  17. Symptoms are an optimal target for orthostatic hypotension screening and management: an argument in favor.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026
    Review
  18. How to treat cardiovascular autonomic failure in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  19. Review
  20. Review

54 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Horacio KaufmannFrom 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.
Roy FreemanFrom 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.
Italo BiaggioniFrom 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.
Phillip LowFrom 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.
Simon PedderFrom 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.
L Arthur HewittFrom 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.
Joe MauneyFrom 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.
Michael FeirtagFrom 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.
Christopher J MathiasFrom 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.
NOH301 Investigators
Curry College · USImperial College London · GBVanderbilt University Medical Center · USNYU Langone Health · US

Funding

Training CoreU54NS065736 · NINDS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BIAGGIONI, ITALO · 2009 to 2018
$11.6M
Carbidopa for the treatment of nausea and vomiting in familial dysautonomiaIND #R01FD003731 · FDA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KAUFMANN, HORACIO · 2009 to 2010
$366k
FDA HHS FD-R-3731-01NINDS NIH HHS U54NS065736)
6 · The paper itself

Abstract

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

methodsPatients 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.

resultsFrom 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.

conclusionsIn 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.

Indexed as

AgedAutonomic AgentsAutonomic Nervous System DiseasesBlood PressureDizzinessDouble-Blind MethodDroxidopaFemaleHumansHypotension, OrthostaticMaleMiddle AgedMultiple System AtrophyNervous System DiseasesParkinson DiseasePostureAutonomic AgentsDroxidopa

Identifiers

PMID24944260
PMCPMC4115605
OpenAlexW2153988998

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.