Long article for March 2015 #GeriMedJC

This month, we'll take a look at a double-blind, placebo-controlled trial of droxidopa for neurogenic orthostatic hypotension.  Droxidopa is an oral norepinephrine precursor.

Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, Mauney J, Feirtag M, Mathias CJ. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014 Jul 22;83(4):328-35. 

Engage in the discussion on Twitter on March 27, 2015 at 08:00 EDT / 12:00 GMT and don't forget to use the hashtag #GeriMedJC.

Did you know that the live version of #GeriMedJC runs for an hour and is broadcast to nine different hospitals in four different cities via the Ontario Telemedicine Network?  

• Toronto: Mount Sinai Hospital, Sunnybrook Hospital, St. Michael’s Hospital, Baycrest Hospital, North York General Hospital, St. Joseph’s Hospital
• Mississauga: Trillium Hospital
• Kitchener-Waterloo: Grand River Hospital
• Orillia: Soldier's Memorial Hospital

The full text of the article can be found here and the abstract is posted below:

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.