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NCT00046475

A Study for Patients With Neurogenic Orthostatic Hypotension

Completed Phase 4 Results posted Last updated 11 June 2021
What this trial tests

Phase 4 trial testing Midodrine Hydrochloride in Hypotension, Orthostatic in 140 participants. Completed in 24 November 1999.

Timeline
1 December 1997
Primary endpoint
24 November 1999
24 November 1999

Quick facts

Lead sponsorShire
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingdouble
Primary purposetreatment
Enrollment140
Start date1 December 1997
Primary completion24 November 1999
Estimated completion24 November 1999
Sites15 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Shire — full company profile →

Who can join

18 and older, any sex, with Hypotension, Orthostatic. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale Primary · End of 2-week treatment period

Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease.

GroupValue95% CI
Midodrine HCl4.1± 2.9
Placebo5.2± 2.7
Re-analysis of The Post-treatment Score For Item 1 of The OHSA Scale, Excluding Two Sites Primary · End of 2-week treatment period

Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease.

GroupValue95% CI
Midodrine HCl4.3± 2.93
Placebo5.1± 2.76
Change From Baseline in The OHSA Items 2 Through 6 Scores Secondary · From the time of titration until the end of treatment

Items 2 through 6 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of the following symptoms whenever he or she was standing and that improved when he or she sat down or laid down: Item 2 addresses problems with vision (blurring, seeing spots, tunnel vision, etc); Item 3, weakness; Item 4, fatigue; Item 5, trouble concentrating; and Item 6, head or neck discomfort. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseli

Item 2, n= 103, 103
GroupValue95% CI
Midodrine HCl-1.2± 2.5
Placebo-0.2± 2.3
Item 3, n=103, 103
GroupValue95% CI
Midodrine HCl-1.3± 3.2
Placebo-0.4± 2.5
Item 4, n=103, 103
GroupValue95% CI
Midodrine HCl-1.2± 3.2
Placebo-0.4± 2.6
Item 5, n=102, 102
GroupValue95% CI
Midodrine HCl-0.4± 2.7
Placebo0.0± 2.2
Item 6, n=102, 102
GroupValue95% CI
Midodrine HCl-0.8± 2.6
Placebo-0.5± 2.1
Change From Baseline in The OHSA Composite Symptom Score Secondary · From the time of titration until the end of treatment

The OHSA composite symptom score was calculated by taking the average of the ratings for the symptoms present at Baseline. Participants were asked to rate symptoms by using a 0-10 scale (0 meaning not bothered and 10 meaning the worst). For subsequent visits, only those symptoms present at Baseline were scored. In this manner, a score was produced that represents the severity (and subsequent change in severity) of the patient's neurogenic OH symptoms, regardless of how many symptoms are presented at Baseline. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6

GroupValue95% CI
Midodrine HCl-1.3± 2.5
Placebo-0.54± 1.952
Change From Baseline in The Orthostatic Hypotension Daily Activity Scale (OHDAS) Items 1 Through 4 Scores Secondary · From the time of titration until the end of treatment

The OHDAS had 4 items that asked the patient to give a graduated score from 0 (no limitation due to OH) to 10 (complete limitation due to OH). Item 1 addressed activities that required standing for a short time; Item 2, activities that required standing for a long time; Item 3, activities that required walking for a short time; and Item 4, activities that required walking for a long time. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved.

Item 1, n=102, 101
GroupValue95% CI
Midodrine HCl-1.1± 2.90
Placebo-0.4± 1.95
Item 2, n=98, 99
GroupValue95% CI
Midodrine HCl-1.8± 3.14
Placebo-0.6± 2.41
Item 3, n=100, 101
GroupValue95% CI
Midodrine HCl-1.1± 2.71
Placebo-0.2± 2.16
Item 4, n=89, 90
GroupValue95% CI
Midodrine HCl-1.3± 3.31
Placebo-0.5± 2.57
Change From Baseline in The Orthostatic Hypotension Global Daily Activity Score Secondary · From the time of titration until the end of treatment

The OHDAS global daily activity score was calculated as the average of all daily activity item scores. The OHDAS had 4 items that asked the patient to give a graduated score from 0 (no limitation due to OH) to 10 (complete limitation due to OH) to activities that required standing for a short time, standing for a long time, walking for a short time, walking for a long time. Symptomatology was assessed at Visit 3A (titration), Visit 5 (Period 2), and Visit 6 (study completion). A negative change from baseline indicates that symptoms have improved.

GroupValue95% CI
Midodrine HCl-1.4± 2.6
Placebo-0.4± 1.9
Percent of Participants Scored as Improved on The Clinician Version of The Clinical Global Impressions Improvement (CGI-I) Scale Secondary · From the time of titration until the end of treatment

The CGI-I is a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Clinical Global Impressions ratings are completed with respect to neurogenic OH symptoms. A value of 0 was used if the investigator or patient assessment was not performed. The improved category is made up of patients who were evaluated as very much improved, much improved, or slightly improved for the classification of "Overall Improvement." The CGI-I was completed at Visit 5 (Period 2) and Visit 6 (study completion).

GroupValue95% CI
Midodrine HCl73.1
Placebo45.2
Percent of Participants Scored as Improved on The Patient Version of The CGI-I Scale Secondary · From the time of titration until the end of treatment

The CGI-I is a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Clinical Global Impressions ratings are completed with respect to neurogenic OH symptoms. A value of 0 was used if the investigator or patient assessment was not performed. The improved category is made up of patients who were evaluated as very much improved, much improved, or slightly improved for the classification of "Overall Improvement." The CGI-I was completed at Visit 5 (Period 2) and Visit 6 (study completion).

GroupValue95% CI
Midodrine HCl62.5
Placebo50.0
Change From Baseline in Standing Blood Pressure (BP) Secondary · From the time of titration until the end of treatment

Standing BP was measured at Visit 5 (Period 2) and Visit 6 (study completion) and compared to measurements taken at Visit 3A (titration). Standing BP was measured 3 minutes after the patient rose from the supine position or as soon as the patient indicated they needed to sit down. If the patient indicated he or she needed to sit down, the BP measurement was taken while in the standing position, before the patient sat down.

Systolic Pressure
GroupValue95% CI
Midodrine HCl10.7± 21.68
Placebo2.8± 19.55
Diastolic Pressure
GroupValue95% CI
Midodrine HCl5.9± 14.46
Placebo1.5± 13.03
Change From Baseline in Supine BP Secondary · From the time of titration until the end of treatment

Supine BP was measured at Visit 5 (Period 2) and Visit 6 (study completion) and compared to measurements taken at Visit 3A (titration). Supine BP was measured after the patient had been in the supine position for 5 minutes.

Systolic Pressure
GroupValue95% CI
Midodrine HCl7.6± 22.76
Placebo-0.9± 15.74
Diastolic Pressure
GroupValue95% CI
Midodrine HCl3.4± 11.89
Placebo0.3± 10.35
Change From Baseline in Short Form-36 (SF-36) Version 2 Health Survey Questionnaire Scores Secondary · From the time of titration until the end of treatment

The SF-36 consists of 36 items in eight domains: physical functioning, general health, role-physical, bodily pain, vitality, social functioning, role-emotional, and mental health. Version 2 references "one week ago" for some questions. Raw scale scores for the SF-36 were transformed to a 0-100 scale with a higher score indicating a better quality of life. A positive change from baseline indicates that symptoms have improved. The SF-36 was completed at Visit 5 (Period 2) and Visit 6 (study completion) and compared to the score from Visit 3A (titration).

General Health
GroupValue95% CI
Midodrine HCl1.97± 7.801
Placebo1.59± 6.027
Physical Functioning
GroupValue95% CI
Midodrine HCl1.99± 8.255
Placebo1.71± 8.034
Test Reliability of the Intent-to-Treat (ITT) Population Secondary · From the time of titration until the end of treatment

Item 1 of the OHSA, the OHSA composite score, and the OHDAS global daily activity score were analyzed for test-retest reliability as a measure of validity. Test-retest reliability is the Pearson product-moment correlation coefficient calculated between OHQ scores at Visit 3A (baseline measure) and OHQ scores at Visit 5 for the subjects who received Placebo during Randomization Period 1.

OHSA Item 1
GroupValue95% CI
ITT Population0.53
OHSA Composite Score
GroupValue95% CI
ITT Population0.61
OHDAS Global Daily Activity Score
GroupValue95% CI
ITT Population0.66

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Screening/Washout
Serious: 1/140 (1%)
Deaths:
Titration
Serious: 4/136 (3%)
Deaths:
Midodrine HCl
Serious: 0/104 (0%)
Deaths:
Placebo
Serious: 1/105 (1%)
Deaths:
Follow-up
Serious: 5/140 (4%)
Deaths:

Serious adverse events (11 terms)

ReactionSystemScreening/WashoutTitrationMidodrine HClPlaceboFollow-up
Cardiac arrestCardiac disorders
Blindness corticalEye disorders
Colitis NOSGastrointestinal disorders
Gastrointestinal haemorrhage NOSGastrointestinal disorders
Injury NOSInjury, poisoning and procedural complications
Therapeutic agent poisoningInjury, poisoning and procedural complications
Neck painMusculoskeletal and connective tissue disorders
Convulsions NOSNervous system disorders
Parkinson's disease NOSNervous system disorders
SyncopeNervous system disorders
Orthostatic hypotensionVascular disorders
Other adverse events (6 terms — click to expand)

ReactionSystemScreening/WashoutTitrationMidodrine HClPlaceboFollow-up
Headache NOSNervous system disorders
Pruritus NOSSkin and subcutaneous tissue disorders
ParaesthesiaNervous system disorders
Hypertension NOSVascular disorders
Urinary tract infection NOSInfections and infestations
DizzinessNervous system disorders

Most-reported serious reactions: Cardiac arrest, Blindness cortical, Colitis NOS, Gastrointestinal haemorrhage NOS, Injury NOS, Therapeutic agent poisoning, Neck pain, Convulsions NOS.

Data from ClinicalTrials.gov NCT00046475 adverse events section.

Sponsor's own description

We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease. The purpose of this clinical study is to further assess the clinical benefit of midodrine hydrochloride (ProAmatine®), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine® or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down and standing positions will be measured at each visit.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Pharmacological Interventions for Orthostatic Hypotension: A Systematic Review.
    Verma A, Saraya E, Haque MS, Senaratne M, et al · · 2025 · PMID 40951129 · DOI 10.7759/cureus.89911

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