title: Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study.
abstract: Midodrine hydrochloride is a short-acting pressor agent that raises blood pressure in the upright position in patients with orthostatic hypotension. The US Food and Drug Administration's Subpart H approval, under which midodrine was initially approved, requires post-marketing studies to confirm midodrine's clinical benefit in this indication. The purpose of this study was to evaluate the clinical benefit of midodrine with regard to symptom response.
  
  
  
  This was a double-blind, placebo-controlled, randomized, crossover, multicenter study (NCT01518946). Following screening, patients aged ≥18 years with severe symptomatic orthostatic hypotension and on a stable dose of midodrine for at least 3 months were randomized to treatment with either their previous midodrine dose or placebo on day 1 and the respective alternate treatment on day 2. The primary endpoint measured time to syncopal symptoms or near-syncope using a 45-min tilt-table test at 1 h post-dose.
  
  
  
  Thirty-three patients were screened for inclusion: 19 received at least one dose of midodrine and had at least one post-dose measurement of the primary endpoint. The least-squares mean time to syncopal symptoms or near-syncope after tilt-table initiation (mean ± standard error) was 1626.6 ± 186.8 s for midodrine and 1105.6 ± 186.8 s for placebo (difference, 521.0 s; 95 % confidence interval 124.2-971.7 s; p = 0.0131). There were 15 adverse events in 10 patients; all of these were mild or moderate in severity, with none considered by the investigators to be related to midodrine.
  
  
  
  Midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension.
authors.affiliation: Volunteer Research Group, University of Tennessee Medical Center, Knoxville, TN, USA.
authors.forename: William
authors.initials: W
authors.lastname: Smith
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wan
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Much
authors.affiliation: Barclay Consulting LLC, Ardmore, PA, USA.
authors.forename: Antoine G
authors.initials: AG
authors.lastname: Robinson
authors.affiliation: Shire, Lexington, MA, USA. pmartin@shire.com.|Global Clinical Pharmacology & Pharmacokinetics, Shire, 300 Shire Way, Lexington, MA, 02421, USA. pmartin@shire.com.
authors.forename: Patrick
authors.initials: P
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008879:Midodrine / Q000009:adverse effects / Q000627:therapeutic use*; D016683:Supine Position; D018667:Tilt-Table Test; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents; D008879:Midodrine
keywords: Clinical trial; Midodrine; Orthostatic hypotension