The RADIAL-TAVI study (DRKS-trial DRKS00035968, NCT 07399392) is an investigator-initiated trial designed and conducted by the University Heart Center Freiburg-Bad Krozingen. The academic research institution Cardiovascular Center for Clinical Research (CCRC) at the University Heart Center Freiburg · Bad Krozingen and the Stiftung Institut für Herzinfarktforschung supported trial coordination and management. The study protocol adheres to the Declaration of Helsinki and was approved by the institutional ethic committees at each participating center. Each subject will provide written informed consent prior to randomization.

The study is designed to investigate whether radial secondary access is superior to femoral access regarding vascular and bleeding complications in patients in the first 30 days after undergoing transfemoral TAVI.

The RADIAL-TAVI trial is a prospective, controlled, randomized, parallel group, open-label, multicenter trial and will be conducted at 7 centers in Germany and Switzerland. Patients with aortic valve stenosis who have been deemed eligible by the heart team and are scheduled for transfemoral TAVI will be included in the study. A total of 434 patients will be randomized in a 1:1 ratio to receive either radial or femoral secondary access. The study flowchart is shown in Figure 1 . Random permuted blocks will be employed to ensure approximate balance of treatment allocation within each site.

Study flow chart of the RADIAL-TAVI trial.

For eligibility, all participants must be diagnosed with aortic valve stenosis and scheduled for a transfemoral TAVI procedure. The decision for TAVI must have been reached and approved by a multidisciplinary heart team. Additionally, all patients must be 18 years of age or older and must provide written informed consent to participate in the study. Patients will be excluded from the study if a radial artery is deemed inaccessible by the TAVI team, or if the femoral arteries are not considered viable for secondary access. Additionally, individuals with anticipated difficulties in achieving primary femoral access (e.g., a “hostile access” anatomy) will be excluded. The study will not include patients who are in a state of hemodynamic instability or cardiogenic shock, or those currently enrolled in another investigational drug or device trial. Finally, individuals who are unable to provide informed consent or who refuse to undergo TAVI will also be ineligible. A complete overview of inclusion and exclusion criteria is shown in Table 1 .

The transfemoral access will be used for the procedure, following current guidelines and the standard techniques of the center. The recommended antithrombotic therapy during the TAVI procedure is unfractionated heparin at a dosage of 50 to 70 IU/kg of body weight, though this can be adjusted to meet the specific medical needs of the patient. Following the procedure, the post-TAVI antithrombotic regimen will be managed according to the institution’s standard protocols.

All patients enrolled in the study will be scheduled to complete the follow-up to evaluate long-term results.

No study-specific procedures will be conducted after the TAVI. Instead, patients will be monitored according to the standard institutional protocols, which include regular clinical and laboratory assessments. Routine monitoring will include a 12-lead ECG, performed immediately after the procedure, again at 24 hours, and prior to discharge. Laboratory tests will cover a full spectrum of blood work, including a complete blood count (hemoglobin, hematocrit, platelet count, white blood cell count), markers for liver and kidney function (bilirubin, albumin, GOT, GPT, creatinine, GFR), and cardiac-specific enzymes (CK, CK-MB, troponin, NT-proBNP). C-reactive protein (CRP) and INR will also be measured. In addition, a comprehensive transthoracic echocardiogram will be performed to evaluate both valve and left ventricular function. This will include measurements of valve gradients, aortic valve area (AVA), regurgitation, prosthesis orifice area, and stroke volume index (SVI). The patient’s vital status, functional status (using the NYHA classification), and current cardiac medication regimen will also be assessed. Finally, the clinical team will monitor for any serious adverse events (SAEs), with a specific focus on bleeding and vascular complications.

Following hospital discharge, all patients will be clinically followed with a phone call at 30 days after randomization. This telephone interview will assess for symptoms such as shortness of breath, chest pain, fatigue, and syncope. The call will also inquire about any adverse events of special interest, including rehospitalizations, bleeding episodes, vascular complications, and compliance with cardiac medication. Additionally, the EQ-5D-5L questionnaire will be completed during this interview to evaluate the patient’s health status.

All patients will be followed by telephone call at 12 months after randomization to obtain the vital status.

The primary endpoint is the incidence of vascular and bleeding complications according to the VARC-3 criteria at the secondary vascular access site until 30 days after randomization. Key secondary endpoints are VARC-3 early safety, cardiovascular mortality, mortality related to vascular and bleeding complications, quality of life assessed by EQ-5D-5L questionnaire at 30 days and freedom from Major Adverse Cardiac Events (MACE) at 30 days. A complete list of all endpoints is provided in Table 2 .

The required sample size was determined to achieve a statistical power of 80% (1−β = 0.8) to detect a significant difference in the primary endpoint between the study groups. The calculation assumed a 1:1 randomization ratio and was performed using a 2-sided chi-squared test with a significance level (α) of 0.05. Based on these parameters, and assuming an incidence of the primary endpoint of 8% in the control (femoral) arm and 2% in the interventional (radial) arm, a total sample size of 412 patients is required. To account for a projected 5% dropout rate, a total of 434 patients will be randomized, with the expectation that 412 patients will be available for the primary analysis. The sample size was calculated using the POWER procedure in SAS/STAT software. The primary analysis of the study will be conducted on the intention-to-treat population.

We will analyze patient data using descriptive statistics. Continuous variables will be summarized with either means and standard deviations or medians and interquartile ranges, as appropriate. Categorical variables will be presented as absolute numbers and percentages. The primary hypothesis will be tested using a 2-sided chi-squared test, with a significance level of 5%. All analyses of secondary endpoints will be exploratory. We will estimate cumulative incidences for event-based endpoints at 30 days and 12 months after randomization, accounting for competing risks. The effect of the intervention on these secondary endpoints will be reported using hazard ratios and 95% confidence intervals. To assess safety, we will summarize all SAEs that occur during or after randomization. SAEs will be presented as frequencies and percentages, stratified by their severity and causal relationship to the procedure. Additional details regarding these statistical methods will be provided in a formal Statistical Analysis Plan (SAP), which will be finalized before the completion of patient recruitment.