Orthostatic; Hypotension, Neurogenic
Conditions
Brief summary
Compare the effect of treatment of midodrine and pyridostigmine in neurogenic orthostatic hypotension and investigate the quality of life of treatment of neurogenic orthostatic hypotension.
Detailed description
In patients with neurogenic orthostatic hypotension, the appropriate treatment was identified by comparing the treatment effects and side effects for each treatment drug. In addition, by confirming the effect of orthostatic hypotension on lowering the quality of life, it is expected that the improvement of the quality of life will help.
Interventions
Sponsors
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* age \>=18 patients who complained of dizziness * Orthostatic hypotension after 3-minute standing (systolic blood pressure drop \>=20 or diastolic blood pressure drop \>=10
Exclusion criteria
* Drug-induced hypotension, if necessary, evaluate patient after discontinuing the causative drug for one month * Heart failure or Chronic renal failure * Patients who cannot or do not want to write questionaires. * Poor drug compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Orthostatic BP Drop | after 3-month medical treatment | Change of orthostatic SBP and DBP drop after 3-month medical treatment compared to initial results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)). | after 3-month medical treatment. | Change of the OH associated symptom survey result after 3-month medical treatment compared to initial results. OHQ questionnaire has two components: the OH daily activity scale (OHDAS), which contains 4 items measuring the impact of OH on daily activities, and the OH symptom assessment (OHSA), which contains 6 items measuring the symptoms of OH (dizziness/light headedness, vision disturbance, weakness, fatigue, trouble concentrating, and head/neck discomfort).This questionnaire reflects the severity of OH-related symptoms on a 10-point scale, with 0 indicating the absence of a symptom and 10 indicating maximal severity. \*\* OHQ total score minimal 0 \ maximal 100 |
| Change of the Depression Score (Beck Depression Inventory-II ) | after 3-month medical treatment. | Change of the depression score after 3-month medical treatment compared to initial results. 21 multiple-choice questions, each of which can be scored from 0 to 3. Higher score represent higher degree of depression. Score Normal; 0-13, Mild depression; 14-19, Moderate depression; 20-28, Severe depression; 29-63 |
| Short-form 36 Version 2 | changes at 3 months after treatment | changes in Short Form (36) Health Survey version 2 (SF-36v2) physical component summary scale (PCS) compared to the baseline SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores. |
| Changes in Health-related Quality of Life | changes at 3 months after treatment | changes in Short Form (36) Health Survey version 2 (SF-36v2) mental component summary scale (MCS) SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Midodrine Only Start midodrine 2.5mg bid, and then dose up to 5mg bid after one month if necessary. | 29 |
| Pyridostigmine Only Start Pyridostigmine 30mg bid, and then dose up to 60mg bid after one month if necessary. | 29 |
| Midodrine + Pyridostigmine Start midodrine 2.5mg bid+ Pyridostigmine 30mg bid, and then dose up to midodrine 5mg bid+ Pyridostigmine 60mg bid after one month if necessary. | 29 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 |
| Overall Study | Lost to Follow-up | 6 | 6 | 6 |
Baseline characteristics
| Characteristic | Midodrine Only | Pyridostigmine Only | Midodrine + Pyridostigmine | Total |
|---|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 17.7 | 59.7 years STANDARD_DEVIATION 13.4 | 52.7 years STANDARD_DEVIATION 16.2 | 57.2 years STANDARD_DEVIATION 16 |
| Orthostatic diastolic blood pressure change | -13.4 mmHg STANDARD_DEVIATION 9 | -15.5 mmHg STANDARD_DEVIATION 9.9 | -13.4 mmHg STANDARD_DEVIATION 8.2 | -14.1 mmHg STANDARD_DEVIATION 9 |
| Orthostatic systolic blood pressure change | -24.7 mmHg STANDARD_DEVIATION 9.9 | -23.3 mmHg STANDARD_DEVIATION 12.5 | -22.5 mmHg STANDARD_DEVIATION 10.1 | -23.5 mmHg STANDARD_DEVIATION 10.8 |
| Region of Enrollment Korea, Republic of | 29 participants | 29 participants | 29 participants | 87 participants |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 15 Participants | 46 Participants |
| Sex: Female, Male Male | 15 Participants | 12 Participants | 14 Participants | 41 Participants |
| Supine diastolic blood pressure | 83.2 mmHg STANDARD_DEVIATION 12.8 | 76.5 mmHg STANDARD_DEVIATION 9.8 | 76.9 mmHg STANDARD_DEVIATION 10.4 | 78.9 mmHg STANDARD_DEVIATION 11.4 |
| Supine heart rate | 68.0 Beats per Minute STANDARD_DEVIATION 11.3 | 66.7 Beats per Minute STANDARD_DEVIATION 13.5 | 67.0 Beats per Minute STANDARD_DEVIATION 10.7 | 67.2 Beats per Minute STANDARD_DEVIATION 11.8 |
| Supine systolic blood pressure | 137.3 mmHg STANDARD_DEVIATION 20.9 | 124.5 mmHg STANDARD_DEVIATION 18.5 | 122.0 mmHg STANDARD_DEVIATION 15.6 | 127.9 mmHg STANDARD_DEVIATION 19.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 29 | 6 / 29 | 3 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 | 0 / 29 |
Outcome results
Primary
Change in Orthostatic BP Drop
Change of orthostatic SBP and DBP drop after 3-month medical treatment compared to initial results.
Time frame: after 3-month medical treatment
Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Midodrine Only | Change in Orthostatic BP Drop | Changes in SBP drop | 11.1 mmHg | Standard Deviation 16.9 |
| Midodrine Only | Change in Orthostatic BP Drop | Changes in DBP drop | 7.5 mmHg | Standard Deviation 15.3 |
| Pyridostigmine Only | Change in Orthostatic BP Drop | Changes in SBP drop | 13.6 mmHg | Standard Deviation 20.1 |
| Pyridostigmine Only | Change in Orthostatic BP Drop | Changes in DBP drop | 11.1 mmHg | Standard Deviation 17.7 |
| Midodrine + Pyridostigmine | Change in Orthostatic BP Drop | Changes in SBP drop | 8.9 mmHg | Standard Deviation 9.9 |
| Midodrine + Pyridostigmine | Change in Orthostatic BP Drop | Changes in DBP drop | 7.4 mmHg | Standard Deviation 14.2 |
Secondary
Change of the Depression Score (Beck Depression Inventory-II )
Change of the depression score after 3-month medical treatment compared to initial results. 21 multiple-choice questions, each of which can be scored from 0 to 3. Higher score represent higher degree of depression. Score Normal; 0-13, Mild depression; 14-19, Moderate depression; 20-28, Severe depression; 29-63
Time frame: after 3-month medical treatment.
Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Midodrine Only | Change of the Depression Score (Beck Depression Inventory-II ) | -6.8 points | Standard Deviation 5.6 |
| Pyridostigmine Only | Change of the Depression Score (Beck Depression Inventory-II ) | -7.8 points | Standard Deviation 6.5 |
| Midodrine + Pyridostigmine | Change of the Depression Score (Beck Depression Inventory-II ) | -3.5 points | Standard Deviation 8 |
Secondary
Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)).
Change of the OH associated symptom survey result after 3-month medical treatment compared to initial results. OHQ questionnaire has two components: the OH daily activity scale (OHDAS), which contains 4 items measuring the impact of OH on daily activities, and the OH symptom assessment (OHSA), which contains 6 items measuring the symptoms of OH (dizziness/light headedness, vision disturbance, weakness, fatigue, trouble concentrating, and head/neck discomfort).This questionnaire reflects the severity of OH-related symptoms on a 10-point scale, with 0 indicating the absence of a symptom and 10 indicating maximal severity. \*\* OHQ total score minimal 0 \ maximal 100
Time frame: after 3-month medical treatment.
Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Midodrine Only | Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)). | -16.2 points | Standard Deviation 15.5 |
| Pyridostigmine Only | Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)). | -17.2 points | Standard Deviation 20.3 |
| Midodrine + Pyridostigmine | Change of the Orthostatic Hypotension Associated Symptom Questionnaire (OH Questionnaire (OHQ)). | -12.6 points | Standard Deviation 14.8 |
Secondary
Changes in Health-related Quality of Life
changes in Short Form (36) Health Survey version 2 (SF-36v2) mental component summary scale (MCS) SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores.
Time frame: changes at 3 months after treatment
Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Midodrine Only | Changes in Health-related Quality of Life | 5.0 points | Standard Deviation 8.6 |
| Pyridostigmine Only | Changes in Health-related Quality of Life | 6.7 points | Standard Deviation 8.9 |
| Midodrine + Pyridostigmine | Changes in Health-related Quality of Life | 0.4 points | Standard Deviation 11.2 |
Secondary
Short-form 36 Version 2
changes in Short Form (36) Health Survey version 2 (SF-36v2) physical component summary scale (PCS) compared to the baseline SF-36v2 measures eight HRQOL domains (physical functioning, role limitation caused by physical problems, bodily pain, general health, vitality, social functioning, role limitation caused by emotional problems, and mental health) summarized into two summary scales that are normalized to the population (mean=50, standard deviation=10): the physical component summary scale (PCS) and the mental component summary scale (MCS).20 Better HRQOL is reflected by higher SF-36v2 scores.
Time frame: changes at 3 months after treatment
Population: At 3 months after treatment, 65 patients were evaluated (Midodrine only; 23, Pyridostigmine only; 21, Midodrine + Pyridostigmine; 21). 22 additional patients missed visit (Midodrine only; 6, Pyridostigmine only; 8, Midodrine + Pyridostigmine; 8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Midodrine Only | Short-form 36 Version 2 | 5.6 points | Standard Deviation 6.8 |
| Pyridostigmine Only | Short-form 36 Version 2 | 4.2 points | Standard Deviation 9.1 |
| Midodrine + Pyridostigmine | Short-form 36 Version 2 | 2.7 points | Standard Deviation 7 |