NCT00555880

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

Completed Phase 4 Results posted Last updated 14 June 2021

What this trial tests

Phase 4 trial testing Midodrine hydrochloride in Hypotension, Orthostatic in 24 participants. Completed in 21 March 2005.

Timeline

8 September 2004

Primary endpoint
21 March 2005

21 March 2005

Quick facts

Lead sponsor	Shire
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	treatment
Enrollment	24
Start date	8 September 2004
Primary completion	21 March 2005
Estimated completion	21 March 2005
Sites	11 locations across United States

Drugs / interventions tested

• Midodrine hydrochloride — full drug profile →
• Placebo

Conditions studied

• Hypotension, Orthostatic — all drugs for Hypotension, Orthostatic →

Sponsor

Shire — full company profile →

Who can join

19 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.

Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Primary · 1 hour post-dose

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 s

Group	Value	95% CI
Midodrine HCl	551.3	± 115.63
Placebo	461.0	± 190.74

Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Secondary · 1 hour post-dose

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 s

Group	Value	95% CI
Midodrine HCl	544.3	± 122.34
Placebo	447.9	± 199.31

Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2 Secondary · 1 hour post-dose

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

Group	Value	95% CI
Midodrine HCl	545.1	± 36.90
Placebo	447.2	± 36.90

Time to Near-syncopal Symptoms at Treatment Visit 1 Secondary · 1 hour post-dose

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 s

Group	Value	95% CI
Midodrine HCl	539.5	± 45.91
Placebo	448.4	± 49.91

Duration of The Effect of Treatment at 3 Hours Post-dose Secondary · 1 and 3 hours post-dose

Duration of effect was defined as the difference in time to onset of near-syncopal symptoms between the first and second tilt table test, conducted at 1 hour and 3 hours post-dose, respectively, at Treatment Visit 2 (time to onset at 3 hours minus time at 1 hour). 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

Group	Value	95% CI
Midodrine HCl	45.1	± 94.03
Placebo	48.0	± 114.96

Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA) Secondary · Approximately 1 hour post-dose

The OHSA measures the severity of six symptoms/symptom complexes associated with orthostatic hypotension. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". The OHSA total score is the sum of six subscales, ranging from 0 (no symptoms) to 60 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjec

Group	Value	95% CI
Midodrine HCl	13.7	± 2.95
Placebo	19.4	± 2.95

Scores for 6 Items of The OHSA Secondary · Approximately 1 hour post-dose

The OHSA measures the severity of six symptoms/symptom complexes associated with OH: dizziness, lightheadedness, and feeling faint; problems with vision; weakness; fatigue; trouble concentrating; and head/neck discomfort. Subjects rated symptoms experienced during the tilt table test on an eleven-point scale from "none" to "worst possible". Scores for each subscale range from 0 (no symptoms) to 10 (worst possible symptoms). The OHSA was completed after the tilt table test was over, but was answered with reference to symptoms experienced during testing. The tilt table test is a 10-minute assess

Dizziness, Lightheadedness, and Feeling Faint

Group	Value	95% CI
Midodrine HCl	3.4	± 3.44
Placebo	4.7	± 3.57

Problems with Vision

Group	Value	95% CI
Midodrine HCl	1.5	± 2.32
Placebo	2.7	± 3.43

Weakness

Group	Value	95% CI
Midodrine HCl	3.0	± 3.13
Placebo	4.1	± 3.17

Fatigue

Group	Value	95% CI
Midodrine HCl	2.7	± 3.22
Placebo	3.5	± 3.48

Trouble Concentrating

Group	Value	95% CI
Midodrine HCl	1.7	± 2.04
Placebo	2.6	± 3.13

Head/Neck Discomfort

Group	Value	95% CI
Midodrine HCl	1.9	± 2.52
Placebo	2.1	± 3.21

Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test Secondary · 1 and 3 hours post-dose

The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The clinician completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. 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 an

Treatment Visit 1- 1 hour post-dose, n=13, 11

Group	Value	95% CI
Midodrine HCl	4
Placebo	4

Treatment Visit 2- 1 hour post-dose, n=11, 13

Group	Value	95% CI
Midodrine HCl	6
Placebo	4

Treatment Visit 2- 3 hour post-dose, n= 11, 12

Group	Value	95% CI
Midodrine HCl	3
Placebo	5

Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test Secondary · 1 and 3 hours post-dose

The CGI-I instrument assesses the overall impression of the subject's orthostatic hypotension during the tilt table test by using a 7-point scale, with 1 being Very much improved; 2, Much improved; 3, Slightly improved; 4, No change; 5, Slightly worse; 6, Much worse; and 7, Very much worse. The patient completed the CGI-I after each of the tilt table tests. A patient was assessed as "Improved" if the score was 1, 2, or 3. 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

Treatment Visit 1-1 hour post-dose, n= 13, 11

Group	Value	95% CI
Midodrine HCl	3
Placebo	2

Treatment Visit 2-1 hour post-dose, n= 11, 13

Group	Value	95% CI
Midodrine HCl	5
Placebo	3

Treatment Visit 2-3 hour post-dose, n= 11, 12

Group	Value	95% CI
Midodrine HCl	3
Placebo	3

Final Blood Pressure During Tilt Table Testing Secondary · 1 hour post-dose

Blood pressure was recorded just before tilt table testing and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. 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 minu

Systolic Pressure

Group	Value	95% CI
Midodrine HCl	106.5	± 37.27
Placebo	90.2	± 24.17

Diastolic Pressure

Group	Value	95% CI
Midodrine HCl	70.6	± 16.44
Placebo	60.6	± 15.04

Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2 Secondary · 1 and 3 hours post-dose

Blood pressure was recorded just before tilt table testing, at each minute during tilt table testing, and immediately after. Timed readings were stopped once a subject experienced near-syncopal symptoms, except for subjects for whom the table was returned to horizontal before 1 minute; for these subjects, a reading was made at 1 minute and was included in analyses. 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

At 1 minute 1 hour post-dose, n= 11, 13

Group	Value	95% CI
Midodrine HCl	142.2	± 44.20
Placebo	97.3	± 24.55

At 1 minute 3 hours post-dose, n= 11, 12

Group	Value	95% CI
Midodrine HCl	110.1	± 19.06
Placebo	94.9	± 31.36

At 10 minutes 1 hour post-dose, n= 10, 8

Group	Value	95% CI
Midodrine HCl	121.7	± 37.57
Placebo	102.9	± 21.03

At 10 minutes 3 hours post-dose, n= 7, 6

Group	Value	95% CI
Midodrine HCl	108.3	± 30.48
Placebo	107.2	± 19.32

Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2 Primary · 1 hour post-dose

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

Group	Value	95% CI
Midodrine HCl	552.4	± 32.93
Placebo	460.0	± 32.93

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.

Midodrine/Placebo

Serious: 1/13 (8%)

Deaths: —

Placebo/Midodrine

Serious: 0/11 (0%)

Deaths: —

Serious adverse events (1 terms)

Reaction	System	Midodrine/Placebo	Placebo/Midodrine
Multiple sclerosis aggravated	Nervous system disorders	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Midodrine/Placebo	Placebo/Midodrine
Hypertension aggravated	Vascular disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Atrioventricular block first degree	Cardiac disorders	—	—
Vomiting NOS	Gastrointestinal disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Dizziness	Nervous system disorders	—	—
Headache NOS	Nervous system disorders	—	—

Most-reported serious reactions: Multiple sclerosis aggravated.

Data from ClinicalTrials.gov NCT00555880 adverse events section.

Sponsor's own description

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.

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