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- Title
Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension.
- Authors
Biaggioni, Italo; Hewitt, L. Arthur; Rowse, Gerald J.; Kaufmann, Horacio; Arthur Hewitt, L
- Abstract
<bold>Background: </bold>Droxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460).<bold>Methods: </bold>Efficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined.<bold>Results: </bold>Droxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 ± 2.20 vs -1.82 ± 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 ± 2.9 vs -1.8 ± 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P ≤ 0.010]). Droxidopa significantly improved 3 of 4 measures of activities of daily living (standing a long time, walking a short time, and walking a long time [P ≤ 0.003]) and significantly increased upright systolic blood pressure (11.5 ± 20.5 vs 4.8 ± 21.0 mmHg for placebo; P < 0.001). Droxidopa was effective in patients using inhibitors of dopa decarboxylase (DDCI; the enzyme that converts droxidopa to norepinephrine), but its efficacy was numerically greater in non-DDCI users. Droxidopa was well-tolerated. Rates of most adverse events were similar between groups. Supine hypertension rates were low, but slightly higher in patients receiving droxidopa (≤7.9% vs ≤4.6% for placebo); patients with severe hypertension at screening were excluded from these studies.<bold>Conclusions: </bold>Droxidopa is effective for the treatment of nOH in patients with primary autonomic disorders and is generally well-tolerated. A longer trial is underway to confirm efficacy beyond the ≤2 to 10 - week period assessed in the current trials.<bold>Trial Registration: </bold>ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.
- Subjects
DROXIDOPA; DRUG efficacy; ORTHOSTATIC hypotension treatment; PARKINSON'S disease; AUTONOMIC nervous system; NORADRENALINE; ANTIPARKINSONIAN agents; BLOOD pressure; COMPARATIVE studies; DIZZINESS; ORTHOSTATIC hypotension; RESEARCH methodology; MEDICAL cooperation; RESEARCH; WALKING; ACTIVITIES of daily living; EVALUATION research; BLIND experiment; THERAPEUTICS
- Publication
BMC Neurology, 2017, Vol 17, p1
- ISSN
1471-2377
- Publication type
journal article
- DOI
10.1186/s12883-017-0867-5