Midodrine and Fludrocortisone for Vasovagal Syncope

Phase

Condition

Low Blood Pressure (Hypotension)

Cataplexy

Dizzy/fainting Spells

Treatment

N/A

Clinical Study ID

NCT04595942

99-2-408-49493

Ages 18-65
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Vasovagal syncope as the cause of transient loss of consciousness (Clinical diagnosisAND Calgary Syncope Symptom Score ≥ -2; Head-up tilt test is not mandatory fordiagnosis)
≥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

Exclusion

Exclusion Criteria:

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, Brugadasyndrome, arrhythmogenic right ventricular cardiomyopathy, complete heart block, andany 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
Previous use of midodrine or fludrocortisone for treatment of VVS or another condition
Pregnancy or breastfeeding

Study Design

November 19, 2020

December 31, 2023

Study Description

Background: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions.

Methods: In the COMFORTS trial, a multi-center randomized controlled trial, 1375 patients with VVS will be randomized into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or just lifestyle modifications. All patients will receive recommendations for lifestyle modifications. In the pharmacological intervention arms, patients will receive 5 mg of midodrine three times a day or 0.1 mg of fludrocortisone twice daily. In case of intolerance, the dosage will be cut by half. If the patient does not tolerate even the reduced dosage, the medication will be discontinued and the patient will be advised to use compression garments, practice tilt training exercises, or switch to the other medication. The patients will be followed on 3, 6, and 12 months after dose stabilization. Primary efficacy outcomes of the study is the time to the first syncopal episode. The secondary efficacy outcome are the recurrence rate of syncope, number of syncopal episodes and the quality of life of the patients which will be assessed by the 36-Item Short Form Survey questionnaire at the enrollment and 12 months after dose stabilization.

Connect with a study center

Tehran Heart Center
Tehran, 1411713138
Iran, Islamic Republic of
Active - Recruiting

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