Midodrine and Fludrocortisone for Vasovagal Syncope (COMFORTS)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04595942 |
|
Recruitment Status :
Recruiting
First Posted : October 22, 2020
Last Update Posted : April 19, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Syncope, Vasovagal | Drug: Midodrine Hydrochloride Tablets Drug: Fludrocortisone Acetate Tablets Behavioral: Lifestyle modification | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 1375 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Comparison of Outcomes With Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS Trial) |
| Actual Study Start Date : | November 19, 2020 |
| Estimated Primary Completion Date : | October 2023 |
| Estimated Study Completion Date : | December 2023 |
| Arm | Intervention/treatment |
|---|---|
|
Active Comparator: Midodrine
10 mg midodrine three times a day
|
Drug: 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).
Other Name: Gutron Behavioral: 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. |
|
Active Comparator: Fludrocortisone
0.1 mg fludrocortisone two times a day
|
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.
Other Name: Florinef Behavioral: 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. |
|
Lifestyle modification
Education, salt and water intake, counter-pressure maneuvers
|
Behavioral: 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. |
- Time to first episode of syncope [ Time Frame: The follow-up continues for 12 months after randomization ]Time from randomization to occurrence of the first episode of vasovagal syncope during the follow-up.
- Recurrence rate of vasovagal syncope [ Time Frame: The follow-up continues for 12 months after randomization ]The proportion of patients who incurred at least one episode of vasovagal syncope during the follow-up.
- Changes in quality of life [ Time Frame: Baseline (It will be evaluated at randomization) and 12 months after randomization. ]It is measured by the 36-item short form (SF-36) questionnaire.
- Major side effects [ Time Frame: The follow-up continues for 12 months after randomization ]The proportion of patients who do not tolerate the initial dosage of medications which leads to either a reduced dosage or discontinuation.
- Minor side effects [ Time Frame: The follow-up continues for 12 months after randomization ]The proportion of patients who experience minor side effects without dosage changes.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04595942
| Contact: Masih Tajdini, MD | +982188029640 | mtajdini@sina.tums.ac.ir |
| Iran, Islamic Republic of | |
| Tehran Heart Center | Recruiting |
| Tehran, Iran, Islamic Republic of, 1411713138 | |
| Contact: Masih Tajdini, MD +982188029640 mtajdini@sina.tums.ac.ir | |
| Study Director: | 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 Chair: | Saeed Sadeghian, MD | Tehran Heart Center, Tehran University of Medical Sciences |
Publications:
| Responsible Party: | Masih Tajdini, MD, Assistant Professor of Cardiology, Tehran Heart Center |
| ClinicalTrials.gov Identifier: | NCT04595942 |
| Other Study ID Numbers: |
99-2-408-49493 |
| First Posted: | October 22, 2020 Key Record Dates |
| Last Update Posted: | April 19, 2021 |
| Last Verified: | April 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Plan Description: | The data is not publicly available due to privacy/ethical restrictions. The data can be shared upon reasonable request to the trial committee, |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
|
Syncope, Vasovagal Syncope Midodrine Fludrocortisone Randomized Controlled Trial |
|
Syncope Syncope, Vasovagal Midodrine Unconsciousness Consciousness Disorders Neurobehavioral Manifestations Neurologic Manifestations Nervous System Diseases Orthostatic Intolerance Primary Dysautonomias Autonomic Nervous System Diseases Fludrocortisone |
Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Vasoconstrictor Agents Adrenergic alpha-1 Receptor Agonists Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Anti-Inflammatory Agents |