NCT04540289

Personalised Risk scOre For Implantation of Defibrillators in Patients With Preserved LVEF>35% and a High Risk for Sudden Cardiac Death

Personalised Risk scOre For Implantation of Defibrillators in Patients With Preserved LVEF>35% and a High Risk for Sudden Cardiac Death (PROFID-Preserved)

• Status: Withdrawn
• Phase: N/A
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Helios Health Institute GmbH · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The objective of the study is to demonstrate that in post-MI patients with preserved LVEF\>35% but high risk for SCD according to a personalised risk score, the implantation of an ICD (index group) is superior to optimal medical therapy (control group) with respect to all-cause mortality.

Detailed description

Sudden cardiac death (SCD) is a major public health problem, causing \~50% of cardiac fatalities and accounting for \~20% of all deaths in Europe. Identification of patients that are at risk for SCD and would benefit from ICD implantation is challenging. A predictor for increased risk of SCD after MI is a severely impaired heart function as expressed by a reduced left ventricular ejection fraction (LVEF). Based on this and on historical landmark trials, which found improved survival in patients with severely reduced LVEF who received an ICD, current clinical guidelines recommend prophylactic ICD implantation in post-MI patients with a LVEF ≤35% to improve overall survival by prevention of SCD. The current use of LVEF as sole patient stratification tool to guide treatment decisions for ICD implantation in patients with prior coronary event, as is currently recommended by clinical guidelines and performed in clinical practice, has significant limitations and results in substantial over- and undertreatment of patients. In particular, there is conclusive evidence that the majority of SCD cases occur in patients with only moderately reduced or preserved LVEF. Thus, with current guidelines most of patients that will develop SCD are not protected by means of ICD implantation. The objective of the study is to demonstrate that in post-MI patients with preserved LVEF\>35% but high risk for SCD according to a personalised risk score, the implanta-tion of an ICD (index group) is superior to optimal medical therapy (control group) with respect to all-cause mortality. PROFID-Preserved is a non-commercial, investigator-driven, prospective, parallel-group, randomised, open-label, blinded outcome assessment (PROBE), multi-centre, superiority trial without dedicated investigational medical device (Proof of Strategy Trial) with two groups with 1:1 randomi-sation. It will be conducted in about 12 European countries with more than 150 clinical sites participating. This study is an event driven trial and the number of randomised patients is estimated to be 1,440, required to collect 297 first primary outcome events within 30 months of mean follow-up. Total study duration: Enrolment of 30 months. All patients will be followed until 297 valid primary endpoints are reached (event-driven trial) which is expected about 15 months after last patient in. Total study duration of 47 months is expected which might be adapted based on a blinded interim analysis of the overall occurrence of the primary endpoint. Individual study duration: Expected median follow-up time will be about 30 months per patient with a minimum follow-up time of 15 months and a maximum follow-up time of presumably 45 months.

Conditions

• Myocardial Infarction
• Sudden Cardiac Death

Interventions

Type	Name	Description
DRUG	Optimal Medical Therapy (OMT)	Patients will be treated according to Optimal Medical Therapy defined by the following guidelines: 1. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes 2. 2016 ESC guidelines for the management of acute and chronic heart failure
DEVICE	Implantable cardioverter-defibrillator (ICD)	An ICD consists of an electronic medical device and electrode leads. The surgery can be performed in local anaesthesia, but a short general anaesthesia is required if the ICD has to be tested giving the patient an electric shock. Besides the possibility to shock during arrhythmias the ICD can potentially terminate ventricular tachycardias by rapid pacing for short periods (small bursts of pacing). The subcutaneous defibrillator is an established and valid alternative to the conventional ICD for the preven-tion of SCD. According to current guidelines, the subcutaneous defibrillator should be considered as an alternative to transvenous defibrillators in patients with an indication for an ICD when pacing therapy for bradycardia support, cardiac resynchronisation or antitachycardia pacing is not needed.

Timeline

• Start date: 2021-02-01
• Primary completion: 2023-01-31
• Completion: 2023-01-31
• First posted: 2020-09-07
• Last updated: 2023-03-08