To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH).
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.
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.
Abbott (2010-present) Alnylam (2012-present Chelsea Pharmaceuticals (2007-present) Johnson and Johnson (2011-present) Pfizer (2001-present) Sanofi-Adventis (2012)
Autonomic Neuroscience - Basic and Clinical, Editor (2007-present) Clinical Autonomic Research, Editorial Board (1999-present) Clinical Journal of Pain, Assoc. Editor, 2009-2012 Clinical Journal of Pain, Editorial Board (2009-present)
U54 NS 065736-03 (Project 3 PI Freeman) 07/01/2009-06/30/2014 NIH/NINDS R01HL109634-01 07/01/2011-06/30/2016 NIH/NHLBI (PI) R01HL111465-01 (Freeman) 09/01/2011-08/31/2015 NIH/NHLBI
1) Chelsea Pharmaceuticals, reimbursement to present at a meeting, unrelated to this study
1) Chelsea Therapeutics, droxidopa 2) Astra Zeneca, ticagrelor 3) Merk, A2A antagonists All unrelated to this study. The consultancy for Chelsea is related to overall drug development of droxidopa.
1) Forest Laboratories, use of nevibolol for supine hypertension in autonomic failure; completed 2) Astra Zeneca, role of adenosine uptake blockade on the effects of ticagrelor; ongoing Both unrelated to this study
NOH301coinvestigators are listed on the Neurology® Web site at Neurology.org.
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