Study to Assess the Benefit of Midodrine in the Treatment of Patients With Neurogenic Orthostatic Hypotension

NCT00555880 | Completed Phase 4 Results

• 1 other identifier: SPD426-404
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this clinical study is to evaluate the clinical effect of midodrine hydrochloride (ProAmatine®) compared to placebo in patients with orthostatic hypotension by measuring the time to onset of near syncopal symptoms and assessing several cardiovascular measurements, such as heart rate, blood pressure, and ECG, using the tilt table test.

Conditions

Hypotension, Orthostatic

Outcome Measures

Primary Outcomes (3)

• Time to Onset of Near-syncopal Symptoms During Tilt Table Testing

  The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.

  1 hour post-dose

• Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2

  The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 1 but the summary data are presented as least squares mean (standard error).

  1 hour post-dose

• Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure

  The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. The Koch procedure is a 3-step process to analyze results while utilizing the available information on magnitude of differences.

  1 hour post-dose

Secondary Outcomes (15)

• Time to Onset of Near-syncopal Symptoms in The Per-protocol Population

  1 hour post-dose

• Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2

  1 hour post-dose

• Time to Near-syncopal Symptoms at Treatment Visit 1

  1 hour post-dose

• Duration of The Effect of Treatment at 3 Hours Post-dose

  1 and 3 hours post-dose

• Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)

  Approximately 1 hour post-dose

Study Arms (2)

1

EXPERIMENTAL

Drug: Midodrine hydrochloride

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Midodrine hydrochloride DRUG

one dose, 10-30mg, given orally

Also known as: ProAmatine

1

Placebo DRUG

Placebo

2

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The male or female subjects must be 18 years of age or older and ambulatory. (Subjects must not require assistance with a walker or wheelchair to perform regular daily activities at all times.)
• Women of childbearing potential must have a negative serum beta HCG pregnancy test at screening and baseline.
• The subject has been diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathy (i.e. neurogenic orthostatic hypotension).
• The subject manifests one of the following symptoms while standing or has a history of one of the following when not treated for orthostatic hypotension: dizziness, lightheadedness, feeling faint or feeling like they may black out.
• The subject is willing and able to undergo the procedures required by this protocol including morning office visits, assessment completion, protocol compliance and participation in the wash-out period.
• The subject has signed an Institutional-Review-Board approved written informed consent form prior to any study procedures taking place.

You may not qualify if:

• The subject is a pregnant or lactating female.
• The subject has pre-existing sustained supine hypertension greater than 180 mm Hg systolic and 110 mm Hg diastolic.
• The subject is taking medications such as vasodilators, pressors, diuretics, ACE inhibitors, angiotensin receptor blockers, beta-blockers, combined alpha and beta-blockers, MAOI's, herbals or specific mixed effect medications.
• The Principal Investigator deems any laboratory test abnormality clinical significant.
• The subject has a diagnosis of any of the following disorders at the time of screening: pheochromocytoma; cardiac conditions including: congestive heart failure within the previous 6 months, myocardial infarction within the previous 6 months, symptomatic coronary artery disease, history of ventricular tachycardia, or uncontrolled cardiac arrhythmias; thyrotoxicosis; uncontrolled diabetes mellitus (uncontrolled defined as a HgbA1c greater than or equal to 10%); history of cerebrovascular accident, transient ischemic attack (TIA) or symptomatic carotid artery stenosis within the previous 6 months; history of coagulopathies; pulmonary hypertension; severe psychiatric disorders; renal failure (Creatinine equal to or greater than 2 times the upper limit of normal)
• The subject has a concurrent chronic or acute illness, disability, or other condition that might confound the results of the tests and/or measurements administered in this trial, or that might increase the risk to the subject.

Sponsors & Collaborators

• Shire: lead

Study Sites (11)

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46805, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Minnesota VA Medical Center

Minneapolis, Minnesota, 55417, United States

Location

Forest Park Neurophysiology

St Louis, Missouri, 63139, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Absher Neurology, PA

Greenville, South Carolina, 29615, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Diabetes and Glandular Disease research Associates, PA

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Hypotension, Orthostatic

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2007
• First Posted: November 9, 2007
• Study Start: September 8, 2004
• Primary Completion: March 21, 2005
• Study Completion: March 21, 2005
• Last Updated: June 14, 2021
• Results First Posted: May 21, 2015

Record last verified: 2021-06

Locations

US (11)