Table e-2. Design and Baseline Characteristics of Included Trials

Study / Type of participants / Mean Age (range/ SD) / Intervention / Comparison / Add on treatment / Follow Up / Type of outcomes
RCT crossover (1974)e26 / 87 adult patients with symptomatic orthostatic hypotension (pathologies not described) / ND (17 to 64) / Midodrine 2.5 or 5 mg three times a day. No dose adjustment based on response to treatment / Placebo / ND / 20 days / End points:
- Changes in blood pressure
- Symptoms improvement (headache, fatigue, heavy leg heaviness, lightheadness, dizziness, insomnia)
RCT parallel (1993)e27 / 97 adult patients with symptomatic orthostatic hypotension and a history of syncope or near syncope. (Bradbury Eggleston syndrome (20%), Shy dragger syndrome (18%), Diabetes mellitus (27%), Parkinson’s disease (22%), Other (10%)) / 61 (22-86) / Midodrine, 2.5 mg, 5 mg, or 10 mg, three times a day. No dose adjustment based on response to treatment / Placebo / Fludrocortisone, indomethacin, cardiac glycosides and nondrug therapies permitted in intervention and control arms / 4 weeks / Primary end point:
- Standing systolic blood pressure
- Symptoms associated with orthostatic hypotension.
Secondary end point:
- Standing diastolic blood pressure, supine systolic and diastolic blood pressures and supine and standing pulse rates
RCT crossover (1995)e28 / 8 adult patients with symptomatic orthostatic hypotension. (Bradbury Eggleston syndrome (87%), Shy dragger syndrome (13%)) / 60.4 (SD 13.5) / Midodrine 2,5, 5, 7,5, or
10mg three times a day
Epinefrine 6, 12, 18,or 24mg. Dose was adjusted based on response to treatment / Placebo / Fludrocortisone and nondrug therapies permitted in intervention and control arms / 10 days / Primary end point:
- Supine and standing blood pressure
-Supine and standing pulse rate
Secondary end points:
- Incidence of patient inability to stand
RCT parallel (1997)e29 / 171 adult patients with symptomatic orthostatic hypotension.
(Bradbury Eggleston syndrome (23%), Shy dragger syndrome (25%), Diabetes (23%), Parkinson’s disease (12%), Other (18%)) / 59.4 (SD 15.2) / Midodrine 10mg three times a day. No dose adjustment based on response to treatment / Placebo / Fludrocortisone and nondrug therapies permitted in intervention and control arms / 6 weeks / Primary end point:
- Lightheadedness (score 0-10)
Secondary end points:
-Improvement in standing systolic blood pressure
- Global Symptom improvement (score that combined the components of
lightheadedness, standing time, and energy level, 0-5)
RCT crossover (1998)e30 / 16 adult patients with history of frequent neurocardiogenic syncope / 56 (SD 18) / Midodrine 5mg three times a day. No dose adjustment based on response to treatment / Placebo / ND / 2 months / Primary end point:
-Symptom free days
- Change in BP
Secondary end points:
-Therapeutic response with scale (1-10)
- HRQL (SF-36)
RCT crossover (1998)e31 / 27 adult patients with symptomatic orthostatic hypotension. (Bradbury Eggleston syndrome (51%), Shy dragger syndrome (25%), Diabetes (11%), Parkinsons disease (4%), Other (9%)) / 62 (38-78) / Midodrine 2.5, 10 or 20mg once a day. No dose adjustment based on response to treatment / Placebo / Fludrocortisone (9 patients). / 6 days / Primary end point:
- 1hr post dose systolic blood pressure
Secondary end points:
- Symptom response (score 1-5)
RCT parallel (2001)e32 / 61 adult patients with a history of recurrent neurocardiogenic syncope with positive head-up tilt test / 42.4 (SD 17.2) / Midodrine 5 mg three times a day. Dose increased up to 15 mg three times a day based on patient response / Fluid therapy, salt tablets and counseling / None / 6 months / Primary end point:
Recurrence of syncope or presyncope, starting 3 weeks after initiation of therapy.
Secondary end points:
-HRQL (Endicott) at the time of randomization and after 6 months
-response to treatment on a scale from 0 (no response) to 6 (excellent response)
-time to first syncope or presyncope
-Response to the tilt test
RCT crossover (2005)e5 / 24 adult ambulatory patients with symptomatic orthostatic hypotension. / 60 (23-82) / Midodrine 10-30 mg once day. No dose adjustment based on response to treatment / Placebo / Other treatments allowed except for alpha agonists. / 30 days / Primary end point:
- Time to onset of near-syncopal symptoms on tilt table test
Secondary end points:
- Clinical benefit, Orthostatic Hypotension Symptom Assessment (OHSA) and clinician and subject rated Clinical Global Impression
RCT parallel (2006)e33 / 26 pediatric patients with recurrent vasovagal syncope and positive head-up tilt test. / 12.2 (SD 2.9) / Midodrine 1,25mg two times a day. Dose increased up to 2,5mg twice daily based on patient response / Placebo / Non pharmacological treatment indicated to all patients in both arms. Pharmacological treatment not allowed. / 10 months / Primary end point:
-Vasopressor response in HUT
Secondary end points:
-Syncope recurrence rate
RCT parallel (2009)e7 / 48 pediatric patients with recurrent vasovagal syncope and positive head-up tilt test. / 11 (SD 3) / Midodrine 1,25mg two times a day. Dose increased up to 2,5mg twice daily based on patient response / Fluid therapy, salt tablets and counseling / Non pharmacological treatment indicated to all patients in both arms. Pharmacological treatment not allowed. / 9 months / Primary end point:
-Vasopressor response in HUT
Secondary end points:
-Syncope recurrence rate
RCT crossover (2011)e6 / 28 adult patients with recurrent Vasovagal Syncope / 31 (SD 12) / Midodrine 5mg twice daily / Placebo / Non pharmacological treatment indicated to all patients in both arms. Pharmacological treatment not allowed. / 3 months / Primary end point:
- Syncope recurrence
Secondary end points:
- HRQL (SF-36) and Syncope Functional Status Questionnaire (SFSQ))

ND indicates non described, RCT randomized controlled trial, HRQL health related quality of life