Midodrine and Fludrocortisone for Vasovagal Syncope

NCT ID: NCT04595942

Last Updated: 2021-04-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

1375 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-19

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Syncope, Vasovagal

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Midodrine

10 mg midodrine three times a day

Group Type ACTIVE_COMPARATOR

Midodrine Hydrochloride Tablets

Intervention Type 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).

Lifestyle modification

Intervention Type 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

0.1 mg fludrocortisone two times a day

Group Type ACTIVE_COMPARATOR

Fludrocortisone Acetate Tablets

Intervention Type 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.

Lifestyle modification

Intervention Type 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.

Lifestyle modification

Education, salt and water intake, counter-pressure maneuvers

Group Type OTHER

Lifestyle modification

Intervention Type 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.

Interventions

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Midodrine Hydrochloride Tablets

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).

Intervention Type DRUG

Fludrocortisone Acetate Tablets

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.

Intervention Type DRUG

Lifestyle modification

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.

Intervention Type BEHAVIORAL

Other Intervention Names

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Gutron Florinef

Eligibility Criteria

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Inclusion Criteria

* 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

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, 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
* Previous use of midodrine or fludrocortisone for treatment of VVS or another condition
* Pregnancy or breastfeeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mahidol University

OTHER

Sponsor Role collaborator

Rajaie Cardiovascular Medical and Research Center

OTHER

Sponsor Role collaborator

Tehran Arrhythmia Center

UNKNOWN

Sponsor Role collaborator

Imam Khomeini Hospital

OTHER

Sponsor Role collaborator

AJA University of Medical Sciences

OTHER

Sponsor Role collaborator

Urmia University of Medical Sciences

OTHER

Sponsor Role collaborator

Isfahan University of Medical Sciences

OTHER

Sponsor Role collaborator

Shahid Beheshti University of Medical Sciences

OTHER

Sponsor Role collaborator

Ahvaz Jundishapur University of Medical Sciences

OTHER

Sponsor Role collaborator

Tehran Heart Center

OTHER

Sponsor Role lead

Responsible Party

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Masih Tajdini, MD

Assistant Professor of Cardiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Arash Jalali, PhD

Role: STUDY_DIRECTOR

Tehran Heart Center, Tehran University of Medical Sciences

Arya Aminorroaya, MD, MPH

Role: STUDY_DIRECTOR

Tehran Heart Center, Tehran University of Medical Sciences

Hamed Tavolinejad, MD

Role: STUDY_DIRECTOR

Tehran Heart Center, Tehran University of Medical Sciences

Saeed Sadeghian, MD

Role: STUDY_CHAIR

Tehran Heart Center, Tehran University of Medical Sciences

Locations

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Tehran Heart Center

Tehran, , Iran

Site Status RECRUITING

Countries

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Iran

Central Contacts

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Masih Tajdini, MD

Role: CONTACT

+982188029640

Facility Contacts

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Masih Tajdini, MD

Role: primary

+982188029640

References

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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.

Reference Type BACKGROUND
PMID: 33689731 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33346809 (View on PubMed)

Other Identifiers

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99-2-408-49493

Identifier Type: -

Identifier Source: org_study_id

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