Trial DesignsComparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial
Section snippets
Ethical considerations and registration
The protocol of this study corresponds to the 1964 Declaration of Helsinki and its later amendments. It has been approved by the ethics committee of Tehran Heart Center at Tehran University of Medical Sciences with the ID of IR.TUMS.THC.REC.1399.028 and will be approved by ethics committees at all participating centers. We will obtain written informed consent from all participants before inclusion in the study. This protocol has been registered at www.clinicaltrials.gov with the ID of
Discussion
In this communication, we presented the detailed protocol of the COMFORTS trial, a multi-center RCT aimed at investigating the efficacy of midodrine versus fludrocortisone with a background of lifestyle modifications for prevention of vasovagal attacks and improving QoL in patients with VVS.
Midodrine is a prodrug that acts through the activation of peripheral alpha-1-adrenergic receptors by its active metabolite, desglymidodrine. It counteracts the venodilation and venous pooling, a consequence
Conclusions
To the best of our knowledge, the COMFORTS trial is the first one which aimed at investigating the efficacy of midodrine, fludrocortisone, and lifestyle modifications for preventing vasovagal spells and improving QoL in patients with VVS. We believe that the results of this study will shed more light on the available pharmacological interventions to improve the outcomes of the patients with VVS.
Declarations of Competing Interest
None.
Acknowledgments
We would like to express our genuine appreciation for the productive suggestions of Professor Michele Brignole, who is the COMFORTS trial advisor and has encouraged us to conduct this study. We thank the invaluable supports and sincere efforts of the staff of the information technology department of Tehran Heart Center for developing the online platform of the study.
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Cited by (3)
Pharmacologic prevention of recurrent vasovagal syncope: A systematic review and network meta-analysis of randomized controlled trials
2023, Heart RhythmCitation Excerpt :The trial conducted by Sheldon et al40 could not determine the efficacy of fludrocortisone in reducing syncopal spells despite a significant effect found in post hoc analyses and following dose stabilization. Overall, it seems that the hypothesis of the superiority of fludrocortisone compared with other drugs, especially midodrine, should be strongly re-evaluated, such as the hypothesis supposed by the COMFORTS (Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope) trial.62 Nonpharmacologic management of VVS should not be forgotten by clinicians.
Compression stockings for treating vasovagal syncope (COMFORTS-II) trial: Rationale and design of a triple-blind, multi-center, randomized controlled trial
2022, American Heart JournalCitation Excerpt :The only non-pharmacological intervention that has been studied in proper RCTs are physical counter-pressure maneuvers,16 which are nevertheless applicable only when prodromes are experienced. Among the various pharmacological options investigated, the oral mineralocorticoid, fludrocortisone, and the alpha-1 adrenergic receptor agonist, midodrine, are most studied.5,19,34 Fludrocortisone did not reduce VVS recurrence in a multicenter trial (Prevention of Syncope Trial-2 [POST-2]), and was only effective in exploratory analysis among patients who tolerated the target 0.2 mg daily dose (only 61% of study population).
Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study
2024, European Journal of Pediatrics
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These authors contributed equally as co-first authors.