Syncope, VasovagalPhase 3COMFORTSNCT04595942
Midodrine and Fludrocortisone for Vasovagal Syncope
A Phase 3 study testing Midodrine Hydrochloride Tablets, Fludrocortisone Acetate Tablets and Lifestyle modification in people with Syncope, Vasovagal, run by Tehran Heart Center at 1 site in Iran.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Syncope, Vasovagal
- What is being tested?
- Midodrine Hydrochloride Tablets, Fludrocortisone Acetate Tablets and Lifestyle modification
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,375 participants
- Where
- 1 siteIran
- Study dates
- 19 Nov 2020to Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Iran1 site, 1 recruiting
- Recruiting
Tehran Heart Center
Tehran, 1411713138
Masih Tajdini, MD, +982188029640, mtajdini@sina.tums.ac.ir
About this study
Official title: Comparison of Outcomes With Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS Trial)
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.
Read the detailed 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.
- Conditions
- Syncope, Vasovagal
- Being tested
- Midodrine Hydrochloride Tablets, Fludrocortisone Acetate Tablets, Lifestyle modification
- Keywords
- Syncope, Vasovagal, Syncope, Midodrine, Fludrocortisone, Randomized Controlled Trial
- Medical subject headings
- Syncope, Vasovagal, Syncope
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Midodrine Hydrochloride TabletsDrug
Also called Gutron
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).
Fludrocortisone Acetate TabletsDrug
Also called Florinef
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 modificationBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Midodrine | Active comparator | 10 mg midodrine three times a day Receives: Drug: Midodrine Hydrochloride Tablets; Behavioral: Lifestyle modification |
| Fludrocortisone | Active comparator | 0.1 mg fludrocortisone two times a day Receives: Drug: Fludrocortisone Acetate Tablets; Behavioral: Lifestyle modification |
| Lifestyle modification | Other | Education, salt and water intake, counter-pressure maneuvers Receives: Behavioral: Lifestyle modification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first episode of syncope
Time from randomization to occurrence of the first episode of vasovagal syncope during the follow-up.
Measured: The follow-up continues for 12 months after randomization
Secondary outcomes (4)
Recurrence rate of vasovagal syncope
The proportion of patients who incurred at least one episode of vasovagal syncope during the follow-up.
Measured: The follow-up continues for 12 months after randomization
Changes in quality of life
It is measured by the 36-item short form (SF-36) questionnaire.
Measured: Baseline (It will be evaluated at randomization) and 12 months after randomization.
Major side effects
The proportion of patients who do not tolerate the initial dosage of medications which leads to either a reduced dosage or discontinuation.
Measured: The follow-up continues for 12 months after randomization
Minor side effects
The proportion of patients who experience minor side effects without dosage changes.
Measured: The follow-up continues for 12 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start19 Nov 2020
- Primary completionOct 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Syncope, VasovagalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,375 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tehran Heart Center
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol University, Rajaie Cardiovascular Medical and Research Center, Tehran Arrhythmia Center, Imam Khomeini Hospital, AJA University of Medical Sciences, Urmia University of Medical Sciences, Isfahan University of Medical Sciences, Shahid Beheshti University of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences
- Responsible party
- Principal investigator, Masih Tajdini, MD, Tehran Heart Center
- Investigators
- Arash Jalali, PhD, Study director, Tehran Heart Center, Tehran University of Medical SciencesArya Aminorroaya, MD, MPH, Study director, Tehran Heart Center, Tehran University of Medical SciencesHamed Tavolinejad, MD, Study director, Tehran Heart Center, Tehran University of Medical SciencesSaeed Sadeghian, MD, Study chair, Tehran Heart Center, Tehran University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04595942
- Sponsor's protocol ID
- 99-2-408-49493
- Acronym
- COMFORTS
- Status last verified
- Apr 2021
- First submitted
- 15 Oct 2020
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data is not publicly available due to privacy/ethical restrictions. The data can be shared upon reasonable request to the trial committee,
Publications
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.
PubMed 33689731Sadeghian 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.
PubMed 33346809
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Outcomes With Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS Trial)
- ClinicalTrials.gov ID
- NCT04595942
- Acronym / sponsor ID
- COMFORTS / 99-2-408-49493
- Conditions
- Syncope, Vasovagal
- Keywords
- Syncope, Vasovagal, Syncope, Midodrine, Fludrocortisone, Randomized Controlled Trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,375 participants (estimated)
- Lead sponsor
- Tehran Heart CenterUniversity, hospital or other
- Collaborators
- Mahidol University, Rajaie Cardiovascular Medical and Research Center, Tehran Arrhythmia Center, Imam Khomeini Hospital, AJA University of Medical Sciences, Urmia University of Medical Sciences, Isfahan University of Medical Sciences, Shahid Beheshti University of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences
- Study start
- 19 Nov 2020 (actual)
- Primary completion
- Oct 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 22 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Midodrine | Active comparator | Drug: Midodrine Hydrochloride Tablets, Behavioral: Lifestyle modification10 mg midodrine three times a day |
| Fludrocortisone | Active comparator | Drug: Fludrocortisone Acetate Tablets, Behavioral: Lifestyle modification0.1 mg fludrocortisone two times a day |
| Lifestyle modification | Other | Behavioral: Lifestyle modificationEducation, salt and water intake, counter-pressure maneuvers |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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%)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Midodrine Hydrochloride TabletsAlso: GutronPatients 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). | Drug | Midodrine |
| Fludrocortisone Acetate TabletsAlso: FlorinefPatients 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. | Drug | Fludrocortisone |
| Lifestyle modificationPatients 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. | Behavioural | Fludrocortisone, Lifestyle modification, Midodrine |
Primary outcome
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.
4 secondary outcomes
Recurrence rate of vasovagal syncope
Time frame: The follow-up continues for 12 months after randomization
Changes in quality of life
Time frame: Baseline (It will be evaluated at randomization) and 12 months after randomization.
Major side effects
Time frame: The follow-up continues for 12 months after randomization
Minor side effects
Time frame: The follow-up continues for 12 months after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Background: PubMed 33689731Aminorroaya 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.
- Background: PubMed 33346809Sadeghian 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.
- Individual participant dataSharing planned: No. The data is not publicly available due to privacy/ethical restrictions. The data can be shared upon reasonable request to the trial committee,
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arash Jalali, PhD study director
Tehran Heart Center, Tehran University of Medical Sciences
Arya Aminorroaya, MD, MPH study director
Tehran Heart Center, Tehran University of Medical Sciences
Hamed Tavolinejad, MD study director
Tehran Heart Center, Tehran University of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Midodrine Hydrochloride Tablets, Fludrocortisone Acetate Tablets and Lifestyle modification in people with Syncope, Vasovagal, run by Tehran Heart Center at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Masih Tajdini, MD (+982188029640, mtajdini@sina.tums.ac.ir), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to first episode of syncope (time frame: The follow-up continues for 12 months after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04595942, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2021.