Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension

a phase 4, double-blind, placebo-controlled, randomized, tilt-table study

William Smith, Hong Wan, David Much, Antoine G. Robinson, Patrick Martin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objective: 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. Methods: 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. Results: 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. Interpretation: Midodrine is a well-tolerated and clinically effective treatment for symptomatic orthostatic hypotension.

Original languageEnglish (US)
Pages (from-to)269-277
Number of pages9
JournalClinical Autonomic Research
Volume26
Issue number4
DOIs
StatePublished - Aug 1 2016

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Midodrine
Orthostatic Hypotension
Placebos
Syncope
Tilt-Table Test
United States Food and Drug Administration
Marketing
Least-Squares Analysis
Cross-Over Studies
Multicenter Studies
Therapeutics
Research Personnel

All Science Journal Classification (ASJC) codes

  • Endocrine and Autonomic Systems
  • Clinical Neurology

Cite this

Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension : a phase 4, double-blind, placebo-controlled, randomized, tilt-table study. / Smith, William; Wan, Hong; Much, David; Robinson, Antoine G.; Martin, Patrick.

In: Clinical Autonomic Research, Vol. 26, No. 4, 01.08.2016, p. 269-277.

Research output: Contribution to journalArticle

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