DR-STEMI is a prospective, open label, European, multicenter randomized-controlled trial which will include 554 patients (277 patients in each treatment arm). Patients with STEMI will be screened on an all-comers basis for study inclusion and exclusion criteria, and those eligible will be allocated randomly 1:1 to dTRA versus TRA approach. The dTRA will be performed through anatomical snuffbox. The study’s protocol has been approved by the local scientific and ethical committee of all the participating sites. The protocol of the study has been preregistered at clinicaltrials.gov (NCT05605288).

Patients aged >18 years old, presenting with STEMI and subjected to primary PCI (pPCI), will constitute the study’s population. The definition of STEMI is according to the recent ESC guidelines. ^,, Table 1 presents the eligibility criteria as well as the exclusion criteria.

Patients meeting all the inclusion and none of the exclusion criteria will be randomized to either dTRA or TRA access. The allocation of patients to the study treatment arms will be performed using a Web-based randomization application ( https://studyrandomizer.com ). Randomization is achieved through a computer-generated random sequence with a random block size. The figure shows the study’s flow– chart.

The usual protocol regarding management of STEMI patients in the catheterization laboratory will be followed. Briefly, intravenous access will be gained in all the patients, for hydration and medication administration. Sterilization of both TRA and dTRA puncture sites will be performed, independently of randomization. The catheterization for the TRA will be applied about 2-3 centimeters proximally to the styloid process in the groove between the tendon of the brachioradialis and the flexor carpi radialis muscles, where the radial artery pulse is better palpable. For patients randomized in dTRA, the puncture will be performed distal to the styloid process through the anatomic snuffbox. Ultrasound guidance for gaining arterial access will be optional and could be used according to the expertise of the operators. The palpability of distal radial artery will not be mandatory. ^, Subcutaneous lidocaine will be administered locally. After the radial artery puncture, a 6- or 7-French sheath will be introduced. Administration of 70-100 IU/kg of unfractionated heparin, according to recent guidelines, will be followed by a bolus of 15cc normal saline and nitroglycerin and/or verapamil according to each center’s standard protocol.

If the initial attempt to obtain arterial access at the randomized access site (dTRA or TRA) lasts for more than 5 minutes, it is recommended that the operator switches to a different access site for safety purposes. In that case, this would be considered as crossover. The crossover site will be up to the discretion of the operator and can include both unilateral or contralateral arteries in the arms or the groins .

After the completion of the procedure, a dedicated radial hemostatic device, will be used applying patent hemostasis based on existing best practice protocols. ^, The successful hemostasis will be evaluated 1 hour after the hemostasis device application for dTRA and 3 hours for conventional TRA access. After 3 hours, if hemostasis has not been achieved, manual compression could be applied.

Only interventional cardiologists with high-experience on dTRA are eligible to participate in DR-STEMI. More specifically, they should have performed at least 100 coronary angiographies ± percutaneous coronary interventions using dRA and at least 20 of them in STEMI patients. Furthermore, their crossover to other access sites should be less than 20%.

The primary endpoint of DR-STEMI is the needle-to-wire time since wire crossing is considered as a critical point for PCI-mediated reperfusion. Needle-to-wire time is defined as the time between the first puncture attempt and the moment the wire crosses through the culprit lesion.

Secondary endpoints include:

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  Radial artery occlusion (RAO), prior to hospital discharge. The RAO will be evaluated in the forearm of the patients by an independent investigator, using the Doppler ultrasound. If no flow signal can be detected in the specific area, then the artery will be considered as occluded.

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  Access site crossover rate. Crossover is defined as a change in access site after 5 minutes of unsuccessful puncture, and its rate is captured as a secondary endpoint.

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  Sheath insertion time (the duration between the first puncture attempt and the successful sheath placement).

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  Total procedure time (the time interval between radial puncture and sheath removal).

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  The time interval between the initiation of radial artery puncture and the completion of coronary angiography.

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  The time for coronary angiography completion, after sheath insertion.

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  The time for percutaneous coronary intervention completion after the completion of coronary angiography.

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  Total fluoroscopy time.

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  Total Dose Area Product (DAP).

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  Air Kerma.

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  Hemostasis time. Hemostasis time is recorded as the duration from hemostatic device placement to successful hemostasis, defined by cessation of bleeding and confirmed by visual inspection.

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  Vascular complications (defined as arteriovenous fistula and pseudoaneurysm formation), and hematomas classification. For hematomas evaluation, the modified EASY classification will be used. More specifically, this modification designated hematomas distal to the styloid process as Ia and hematomas up to 5 cm proximal to the styloid process as Ib, keeping the definitions of the original EASY classification for type II, III, and IV forearm hematomas.

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  Thirty-days clinical follow-up, including major adverse cardiac events and unscheduled PCI. MACE is defined as the composite of nonfatal stroke, nonfatal myocardial infraction and cardiovascular death. The follow– up will be performed thirty days after the procedure and is up to operator’s discretion on whether will be on-site or via telephone call.

The primary hypothesis of the study is that dTRA is noninferior to conventional TRA regarding the required time between the puncture of the radial artery and wire crossing of the infarct-related artery (i.e., needle-to-wire time). In recent randomized trials of femoral versus radial access in STEMI patients, median needle-to-balloon time ranged between 10 and 13 min in the radial arms. ^, Similarly, in the ANGIE randomized study of dTRA versus TRA in patients without STEMI, the mean and median time from artery puncture to completion of coronary angiography was 11.8 ± 6.4 min (median 10 [IQR 8-15] min) versus 10.8 ± 6.5 min (median 9 [IQR 7-12] min), respectively. For a statistical power of 90% and a type 1 error rate of 2.5% (one-sided test), a delta (i.e., expected difference) of 1 min between the 2 strategies with a standard deviation of 6.47 min (based on the data of the ANGIE trial), and with the use of a noninferiority limit of 3 min longer time in the dTRA arm, we calculated a sample size of 221 patients per arm. To allow for a drop-out rate of 20%, the target sample size is set at 277 patients per arm (554 in total). The primary endpoint analysis will be performed on the intention-to-treat population, based upon randomization assignment to either the TRA or the dTRA group. The noninferiority threshold of 3 minutes was selected following precedent from landmark trials in STEMI, where median needle-to-balloon times for radial access ranged between 10 and 13 minutes. A 3-minute margin was considered clinically acceptable based on its minimal impact on myocardial salvage in STEMI patients, aligning with prior guidance on door-to-balloon benchmarks. ^,

All clinical and research staff involved in the trial at each study recruiting center will be managed by the interventional cardiologist selected to participate as the site’s principal investigator. Independent monitoring will be performed throughout the duration of the trial according to Good Clinical Practice (GCP). The data will be entered by the investigator into a dedicated electronic Case Report Form (eCRF). Standard Operating Procedures and regular full backups are in place to ensure that data will not be lost and can be recovered in the event of an equipment failure, unintentional destruction of data or disaster. The eCRF includes all the clinical, periprocedural and follow-up data to be collected for each patient. eCRF access will be done using a personal login and password, which will be changed at least annually. Investigators must maintain information in the study patient’s medical records, which corroborate data collected on the eCRF. Worksheets will be provided for the collection of study-specific data that would not typically be part of the subject’s medical chart. The safety committee of the study will perform quality control of eCRFs every 2 months.

Trial and participants’ data will be handled with the utmost discretion and will only be accessible to authorized personnel. On the CRFs and all other study specific documents, participants will be identified by a unique participant number. The correspondence between numbers and patients will be kept separately. The patient identification list with complete identification information (name, address, contact number) on each patient will remain at the study site in a locked cabinet under the responsibility of the local principal investigator. The investigator will maintain all study documents in strict confidence.

The sponsor of primary investigator (Terumo Europe) had no role in data analysis or interpretation, and the study is investigator-initiated with independent monitoring and endpoint adjudication.