Efficacy and Safety of Midodrine and Atomoxetine for Neurogenic OH

NCT03350659 | Completed Phase 4 DMC

• 1 other identifier: 1710-060-893
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This was a randomized, open-label clinical trial. We will enroll patients with symptomatic neurogenic OH and randomize them to 1 of 2 treatments: (1) midodrine only, (2) atomoxetine only. We will follow up patients at 1 and 3 months after treatment. If the patients meet BP criteria for OH at 1 month, they will receive combination treatment with both midodrine and atomoxetin. The primary outcome measure is amelioration of questionnaire score evaluating OH-associated symptoms at 3 months. Secondary end-points were improvement in orthostatic blood pressure (BP) drop at 1 and 3 months.

Conditions

Neurogenic Orthostatic Hypotension

Keywords

orthostatic hypotension; midodrine; atomoxetine; treatment

Outcome Measures

Primary Outcomes (1)

• 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 (subscale OHDAS score minimal 0\~ maximal 40, OHSA score minimal 0\~ maximal 60)

  after 3-month medical treatment

Secondary Outcomes (3)

• Change in Orthostatic blood pressure Drop (mmHg)

  after 3-month medical treatment

• Change of the Depression Score (Beck Depression Inventory-II )

  after 3-month medical treatment

• Changes in Health-related Quality of Life

  after 3-month medical treatment

Study Arms (2)

Atomoxetine

EXPERIMENTAL

Atomoxetine 18mg once a day.

Drug: Atomoxetine

Midodrine

ACTIVE COMPARATOR

midodrine 2.5mg twice a day (increase to 5mg three times a day if necessary)

Drug: Midodrine

Interventions

Midodrine DRUG

Midodrine single 5mg/day

Also known as: Midodrine only

Midodrine

Atomoxetine DRUG

Atomoxetine single 18mg/day

Also known as: Atomoxetine only

Atomoxetine

Eligibility Criteria

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

You may qualify if:

• Age \>=19 patients who complained of dizziness
• Orthostatic hypotension after 3-minute standing (systolic blood pressure drop \>=20 or diastolic blood pressure drop \>=10

You may not qualify if:

• Drug-induced hypotension, if necessary, evaluate patient after discontinuing the causative drug for one month
• Heart failure or Chronic renal failure
• Severe supine hypertension (Systolic Blood Pressure \>180 or Diastolic Blood Pressure\>110mmHg)
• Pregnant women, breast-feeding
• Unable to perform questionnaire

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Kyung Hee University Hospital at Gangdong: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Related Publications (11)

• Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology. 1996 May;46(5):1470. doi: 10.1212/wnl.46.5.1470. No abstract available.

  PMID: 8628505 BACKGROUND

• Smit AA, Halliwill JR, Low PA, Wieling W. Pathophysiological basis of orthostatic hypotension in autonomic failure. J Physiol. 1999 Aug 15;519 Pt 1(Pt 1):1-10. doi: 10.1111/j.1469-7793.1999.0001o.x.

  PMID: 10432334 BACKGROUND

• Hiitola P, Enlund H, Kettunen R, Sulkava R, Hartikainen S. Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older. J Hum Hypertens. 2009 Jan;23(1):33-9. doi: 10.1038/jhh.2008.81. Epub 2008 Jul 24.

  PMID: 18650837 BACKGROUND

• Hale GM, Valdes J, Brenner M. The Treatment of Primary Orthostatic Hypotension. Ann Pharmacother. 2017 May;51(5):417-428. doi: 10.1177/1060028016689264. Epub 2017 Jan 16.

  PMID: 28092986 BACKGROUND

• Low PA, Singer W. Management of neurogenic orthostatic hypotension: an update. Lancet Neurol. 2008 May;7(5):451-8. doi: 10.1016/S1474-4422(08)70088-7.

  PMID: 18420158 BACKGROUND

• Wright RA, Kaufmann HC, Perera R, Opfer-Gehrking TL, McElligott MA, Sheng KN, Low PA. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998 Jul;51(1):120-4. doi: 10.1212/wnl.51.1.120.

  PMID: 9674789 BACKGROUND

• Parsaik AK, Singh B, Altayar O, Mascarenhas SS, Singh SK, Erwin PJ, Murad MH. Midodrine for orthostatic hypotension: a systematic review and meta-analysis of clinical trials. J Gen Intern Med. 2013 Nov;28(11):1496-503. doi: 10.1007/s11606-013-2520-3. Epub 2013 Jun 18.

  PMID: 23775146 BACKGROUND

• Izcovich A, Gonzalez Malla C, Manzotti M, Catalano HN, Guyatt G. Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review. Neurology. 2014 Sep 23;83(13):1170-7. doi: 10.1212/WNL.0000000000000815. Epub 2014 Aug 22.

  PMID: 25150287 BACKGROUND

• Byun JI, Moon J, Kim DY, Shin H, Sunwoo JS, Lim JA, Kim TJ, Lee WJ, Lee HS, Jun JS, Park KI, Lee ST, Jung KH, Jung KY, Lee SK, Chu K. Efficacy of single or combined midodrine and pyridostigmine in orthostatic hypotension. Neurology. 2017 Sep 5;89(10):1078-1086. doi: 10.1212/WNL.0000000000004340. Epub 2017 Aug 9.

  PMID: 28794253 BACKGROUND

• Ramirez CE, Okamoto LE, Arnold AC, Gamboa A, Diedrich A, Choi L, Raj SR, Robertson D, Biaggioni I, Shibao CA. Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2014 Dec;64(6):1235-40. doi: 10.1161/HYPERTENSIONAHA.114.04225. Epub 2014 Sep 2.

  PMID: 25185131 BACKGROUND

• Hale GM, Brenner M. Atomoxetine for Orthostatic Hypotension in an Elderly Patient Over 10 Weeks: A Case Report. Pharmacotherapy. 2015 Sep;35(9):e141-8. doi: 10.1002/phar.1635.

  PMID: 26406777 BACKGROUND

MeSH Terms

Conditions

Hypotension, Orthostatic

Interventions

Midodrine; Atomoxetine Hydrochloride

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; Propylamines

Study Officials

• Chu Kon

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, open-label clinical trial.

Study Record Dates

• First Submitted: November 18, 2017
• First Posted: November 22, 2017
• Study Start: January 1, 2018
• Primary Completion: January 29, 2019
• Study Completion: March 15, 2019
• Last Updated: April 5, 2019

Record last verified: 2019-04

Locations

KR (1)