Midodrine and Fludrocortisone for Vasovagal Syncope

NCT04595942 | Unknown Phase 3 DMC

• 1 other identifier: 99-2-408-49493
• Study Type: interventional
• Target: 1,375
• Locations: 1 country
• Sites: 1

Brief Summary

Syncope is a common condition which can disturb daily functions of the patients and impair their quality of lives. It contributes to 0.8 to 2.4% of the visits of emergency rooms. Noticeably, studies demonstrated that the lifetime prevalence of syncope is as high as 41% with a 13.5% recurrence rate. The cornerstone of the treatment of vasovagal syncope (VVS), the most common type of syncope, is lifestyle modifications and patient education to avoid potential triggers of syncope. These recommendations alleviate vasovagal spells in many patients; however, some patients experience life-disturbing vasovagal attacks despite compliance with these modifications. This fact underscores the importance of efficient pharmacological interventions as well. Currently, there is an ongoing controversy about the efficacy of midodrine and fludrocortisone as adjunct pharmacological interventions for the prevention of VVS. In the COMFORTS trial, we are going to evaluate the efficacy of midodrine, fludrocortisone, and lifestyle modifications for prevention of vasovagal attacks in patients with VVS.

Conditions

Syncope, Vasovagal

Keywords

Syncope, Vasovagal; Syncope; Midodrine; Fludrocortisone; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Time to first episode of syncope

  Time from randomization to occurrence of the first episode of vasovagal syncope during the follow-up.

  The follow-up continues for 12 months after randomization

Secondary Outcomes (4)

• Recurrence rate of vasovagal syncope

  The follow-up continues for 12 months after randomization

• Changes in quality of life

  Baseline (It will be evaluated at randomization) and 12 months after randomization.

• Major side effects

  The follow-up continues for 12 months after randomization

• Minor side effects

  The follow-up continues for 12 months after randomization

Study Arms (3)

Midodrine

ACTIVE COMPARATOR

10 mg midodrine three times a day

Drug: Midodrine Hydrochloride Tablets; Behavioral: Lifestyle modification

Fludrocortisone

ACTIVE COMPARATOR

0.1 mg fludrocortisone two times a day

Drug: Fludrocortisone Acetate Tablets; Behavioral: Lifestyle modification

Lifestyle modification

OTHER

Education, salt and water intake, counter-pressure maneuvers

Behavioral: Lifestyle modification

Interventions

Midodrine Hydrochloride Tablets DRUG

Patients will be started on 5 mg Midodrine three times a day and after one week the dosage will be up-titrated to 10 mg three times a day and continued for 12 months. They will receive the medication at four-hour intervals upon rising in the morning (the last dose should not be taken later than 6 PM). In case of intolerance, the dosage will be reduced to 2.5 mg three times a day. Patients will also receive recommendations for lifestyle modifications including drinking 2 to 3 liters of fluid per day, daily consumption of 10 grams of salt, and practicing counter-pressure maneuvers (handgrip, arm-tensing, leg crossing and squatting).

Also known as: Gutron

Midodrine

Fludrocortisone Acetate Tablets DRUG

Patients will be started on 0.05 mg of fludrocortisone twice daily and after one week the dosage will be up-titrated to 0.1 mg fludrocortisone twice daily taken for 12 months. Patients will also receive recommendations for lifestyle modifications including drinking 2 to 3 liters of fluid per day, daily consumption of 10 grams of salt, and practicing counter-pressure maneuvers (handgrip, arm-tensing, leg crossing and squatting). In this arm, potassium levels will be checked 7-14 days after dose stabilization.

Also known as: Florinef

Fludrocortisone

Lifestyle modification BEHAVIORAL

Patients will be recommended to drink 2 to 3 liters of fluid per day, consume 10 grams of salt per day, and practice counter-pressure maneuvers (handgrip, arm-tensing, leg crossing and squatting) for 12 months.

Fludrocortisone; Lifestyle modification; Midodrine

Eligibility Criteria

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

You may qualify if:

• Vasovagal syncope as the cause of transient loss of consciousness (Clinical diagnosis AND Calgary Syncope Symptom Score ≥ -2; Head-up tilt test is not mandatory for diagnosis)
• ≥2 episodes of syncope during the last year
• Medication-naïve or have at least a 2-week washout period prior to randomization
• The capability of giving informed consent
• Signed written informed consent

You may not qualify if:

• Other causes of transient loss of consciousness including orthostatic hypotension, postural tachycardia, carotid sinus hypersensitivity, or seizure
• Cardiac rhythm disorders including ventricular tachycardia, long QT syndrome, Brugada syndrome, arrhythmogenic right ventricular cardiomyopathy, complete heart block, and any conduction abnormality on electrocardiogram
• Severe valvular heart disease
• Hypertrophic cardiomyopathy
• Cardiac systolic dysfunction (ejection fraction≤40%)
• Obstructive coronary artery disease
• Hypertension
• Diabetes mellitus
• Cirrhosis
• Renal failure stage≥3
• Known intolerance or hypersensitivity to midodrine or fludrocortisone
• Urinary retention
• Pheochromocytoma
• Thyrotoxicosis
• Glaucoma

Sponsors & Collaborators

• Tehran Heart Center: lead
• Mahidol University: collaborator
• Rajaie Cardiovascular Medical and Research Center: collaborator
• Tehran Arrhythmia Center: collaborator
• Imam Khomeini Hospital: collaborator
• AJA University of Medical Sciences: collaborator
• Urmia University of Medical Sciences: collaborator
• Isfahan University of Medical Sciences: collaborator
• Shahid Beheshti University of Medical Sciences: collaborator
• Ahvaz Jundishapur University of Medical Sciences: collaborator

Study Sites (1)

Tehran Heart Center

Tehran, 1411713138, Iran

RECRUITING

Related Publications (2)

• Aminorroaya A, Tavolinejad H, Sadeghian S, Jalali A, Alaeddini F, Emkanjoo Z, Mollazadeh R, Bozorgi A, Oraii S, Kiarsi M, Shahabi J, Akbarzadeh MA, Rahimi B, Joharimoghadam A, Mohsenizade A, Mohammadi R, Oraii A, Ariannejad H, Apakuppakul S, Ngarmukos T, Tajdini M. Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial. Am Heart J. 2021 Jul;237:5-12. doi: 10.1016/j.ahj.2021.03.002. Epub 2021 Mar 6.

  PMID: 33689731 BACKGROUND

• Sadeghian S, Aminorroaya A, Tajdini M. The Syncope Unit of Tehran Heart Center. Eur Heart J. 2021 Jan 7;42(2):148-150. doi: 10.1093/eurheartj/ehaa532. No abstract available.

  PMID: 33346809 BACKGROUND

MeSH Terms

Conditions

Syncope, Vasovagal; Syncope

Interventions

Midodrine; fludrocortisone acetate

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Arash Jalali, PhD

  Tehran Heart Center, Tehran University of Medical Sciences

  STUDY DIRECTOR

• Arya Aminorroaya, MD, MPH

  Tehran Heart Center, Tehran University of Medical Sciences

  STUDY DIRECTOR

• Hamed Tavolinejad, MD

  Tehran Heart Center, Tehran University of Medical Sciences

  STUDY DIRECTOR

• Saeed Sadeghian, MD

  Tehran Heart Center, Tehran University of Medical Sciences

  STUDY CHAIR

Central Study Contacts

Masih Tajdini, MD

CONTACT

+982188029640; mtajdini@sina.tums.ac.ir

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Cardiology

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: October 22, 2020
• Study Start: November 19, 2020
• Primary Completion: October 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 19, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)