Compression Stockings for Treating Vasovagal Syncope Trial

The COMFORTS II study is designed as a multicenter, longitudinal, double blind, parallel design RCT to assess the beneficial effect of compression stockings for preventing recurrences of VVS. The participants will be treated by the standard treatment of VVS, and then they will be randomized into two groups (1:1 ratio) to use compression stockings, one group with 25-30 mm Hg pressure and the other one with <= 10 mmHg pressure, Randomization and allocation concealment will be done by the primary investigators (www.comfortstrial.com). To balance participant enrolment, participating centers will stratify the randomization block. The enrolling physicians will be blinded to the randomization to minimize the selection bias. Hence, the randomization code will not be revealed till the patient has been enrolled, and the baseline features and consent form have been uploaded.

The syncope Unit of Tehran Heart Center (SUTHC), Tehran University of Medical Sciences is the primary investigation site (same as COMFORTS I trial). Seven study centers across Iran declared their commitment to participate in this study. After randomization, participants will be allocated their treatment as one group will have compression stockings with 25-30 mm Hg pressure and in the control group pressure will be limited up to <=10 mmHg, which elastic compression stockings will be sent to patients by post. Participants will be asked to use compression stockings as long as they could (ideal would be the majority of the time they are upright). Adherence of patients to the use of compression stockings will be daily with predefined forms given to patients after randomization. In addition, a CD included some videos and booklets about instructions on how to wear CS and how to keep them will be provided for the participants with their compression stockings. All patients will receive standard treatment of VVS despite their randomization. According to syncope guidelines, patients will learn to drink 2-3 liters of fluids, consume 10 grams 120 mmol/day of sodium chloride, and practice counter-pressure maneuvers (squatting, leg crossing, handgrip, and arm-tensing

After six months of follow-up for 50% of the study participants, event rates will be assessed by the data and safety monitoring board (DSMB) and the sample size can be adjusted based on DSMB guidance

Data safety and monitoring board (DSMB):

a. Roles: i. Monitoring data quality and completeness, as well as timeliness of enrollment, visit, and follow-up, ii. Overseeing adherence to trial protocol and providing feedback in documented reports to the trial committee iii. Overseeing performance of individual centers, and providing feedback in documented reports to the trial committee iv. Monitoring patient safety and their current treatment, and recommending changes in therapies for individuals subjects if needed, v. Advising adjustments to the sample size after interim analysis of data upon completion of six months of follow-up for half of the study sample size, vi. Monitoring scientific or therapeutic developments in the field, and in case of major developments providing updated recommendations on the ethics of the study.

b. Meetings: i. At the start of enrollment ii. Every three months after beginning of enrollment until the final follow-up iii. After formal analysis of the data has been performed iv. The chair of DSMB may call for additional meetings

c. Members: i. Chair: Dr. Haleh Ashraf (Sina Hospital); The chair of DSMB is responsible for conducting meetings, and may add members to the DSMB at her own discretion. ii. Mohammad-Reza Malekpour (Non-communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute) iii. Maryam Masoudi (Roozbeh Psychiatric Hospital)