After extensive 2.5 years, the PROFID data analysis has been completed. The results, which were presented at the ESC Congress 2022 in Barcelona, have significant implications for the setup of the randomized trial programme. We are currently finalizing an updated design of the PROFID clinical trial, in order to start the submissions to the Ethics Committees at the beginning of 2023.
Which findings have been presented at the ESC Congress 2022?
Nikolaos Dagres: “The results of our analysis show that LVEF is only a moderate predictor of sudden cardiac death in patients after myocardial infarction and that other parameters including previously reported candidate predictors, clinical data and CMR measurements did not increase the predictive performance. We also found that overall, the risk for sudden cardiac death is low in patients with LVEF 35% or below and very low in patients with LVEF above 35%.”
What do these results mean for the project?
Nikolaos Dagres: “As we can clearly see, there is a need to discuss and adapt the setup and execution of the clinical trials based on the final results of the data analysis. Considering the huge importance of these decisions for the project itself, but also in the long run for clinical practice, we invited 25 top international key opinion leaders in the field of sudden cardiac death to a face-to-face meeting in Frankfurt in July 2022. Together we looked at the results of the data analysis and discussed their implications for the setup of the trials, to achieve the aim of PROFID: an optimal decision-making on primary prevention ICD implantation after myocardial infarction.”
What does this exactly mean?
Nikolaos Dagres: “According to the results of the data analysis the PROFID-Preserved trial is no longer feasible. Therefore we are going to focus on one trial, the PROFID-Reduced trial, in order to address existing outdated data which do no longer represent current therapies.”
Thomas, you are the CEO of CRI, the clinical research organisation of PROFID. The PROFID trial will start soon. What are your current tasks?
Thomas Fetsch: “First, I would like to take the opportunity to introduce our new leading project manager, Dr. Raphaela Kübeck, because she and her team will perform the upcoming tasks. Based on the recent findings of the PROFID data base analysis and subsequent decisions on study design, the PROFID team at CRI currently adapts study protocol and related procedure descriptions as well as other relevant study documents to the new ‘PROFID’ trial. This involves not only the PROFID study team at CRI, but also regulatory affairs officers, data managers, statisticians, contract specialists, privacy officers, quality managers, controller, and the senior director projects, who take responsibility.
Next step after approval of the new study protocol by the Steering Committee and other documents by the legal sponsor is to inform all study sites and to start submission to Ethics Committees timely. In parallel, negotiations on study contracts will start with the administration of each potential study site.”
Do you have some concrete numbers for us?
Thomas Fetsch: “The new single trial ‘PROFID’ requested a new sample size calculation by the responsible study statistician to reach the still valid goal of 374 primary endpoints according to the biometrical model of the study. This means in numbers: Enrolment and randomization of about 3,600 patients with the help of about 180 participating study sites in 12 European countries within 30 months of recruitment period. First submission to Ethics Committees is aimed to be performed at the beginning of January 2023. First study site initiations will happen immediately after the first approvals, expected earliest end of March 2023, with first patient in (FPI) in April 2023. Subsequent submissions and study site initiations will follow.”
What will be your main challenges during the PROFID trial?
Thomas Fetsch: “The major challenge for conducting the PROFID trial is time. The whole PROFID project is funded by the EU commission with a strictly limited funding period. Thus, fast and adequate enrolment of patients is THE critical challenge for success of the trial and the total project! We all are depending on the efforts spent at each single study site in Europe to recruit and randomize 3,600 patients within 30 months of total enrolment period. Taken into account that set-up of 180 sites in 12 countries will take a while this means a constant enrolment rate of at least about 1 enrolled and randomized patient at each study site within every month of study participation or about 10 to 12 patients per year.”
Nikos, what are the next steps within the PROFID project?
Nikolaos Dagres: “As described, we are currently focusing on the start of the PROFID trial at the beginning of 2023. In addition, we are discussing with the other work package leaders adaptations that might be necessary for their work in PROFID based on the results of the data analysis. We will also finally have a face-to-face consortium meeting in early 2023. The last time we all met in person was 2020. Due to COVID-19, all other meetings have been held online, so we’re looking forward to meeting our great partners soon again.”