Clinical benefit of midodrine hydrochloride in symptomatic orthostatic hypotension: a phase 4, double-blind, placebo-controlled, randomized, tilt-table study.

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.

• Authors: William Smith, Hong Wan, David Much, Antoine G Robinson, Patrick Martin
• Journal: Clinical autonomic research : official journal of the Clinical Autonomic Research Society (Clin Auton Res) Vol. 26 Issue 4 Pg. 269-77 (08 2016) ISSN: 1619-1560 [Electronic] Germany
• PMID: 27372462 (Publication Type: Clinical Trial, Phase IV, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Vasoconstrictor Agents
• Midodrine

Topics

• Adolescent
• Adult
• Aged
• Blood Pressure
• Cross-Over Studies
• Double-Blind Method
• Female
• Humans
• Hypotension, Orthostatic (diagnosis, drug therapy)
• Male
• Middle Aged
• Midodrine (adverse effects, therapeutic use)
• Supine Position
• Tilt-Table Test
• Treatment Outcome
• Vasoconstrictor Agents (adverse effects, therapeutic use)
• Young Adult