Highlights
-
•
DRA is a valid alternative to conventional TRA for coronary angiography and PCI.
-
•
Randomized evidence on large-bore DRA for patients undergoing complex PCI is scarce.
-
•
DISCO COMPLEX is an investigator-initiated RCT of large-bore DRA vs TRA in 708 complex PCI patients.
-
•
The primary hypothesis is that DRA is superior to TRA in reducing radial artery occlusion.
-
•
DISCO COMPLEX is the first RCT testing large-bore DRA vs. TRA in complex PCI with 7-Fr guide catheters.
ABSTRACT
Rationale
Distal radial access (DRA) has emerged as a promising alternative to conventional transradial access (TRA) for coronary angiography and percutaneous coronary intervention (PCI). However, existing randomized evidence on DRA primarily involves low-risk patients undergoing diagnostic angiography or noncomplex PCI using ≤6 French (Fr) introducer sheaths. The clinical benefits of DRA among patients undergoing PCI for complex coronary lesions using large-bore guide catheters remain therefore uncertain.
Design
DISCO COMPLEX is an investigator-initiated, prospective, multicenter, international, open-label, randomized, controlled trial with a blinded outcome assessment and superiority design. The trial will compare in a 1:1 ratio large-bore DRA versus conventional TRA using a 7-Fr introducer sheath in 708 patients undergoing PCI for complex coronary lesions (chronic total occlusions, left main disease, heavily calcified lesions, or complex bifurcations) with a 7-Fr guide catheter. The primary hypothesis is that large-bore DRA is superior to conventional TRA with respect to the incidence of forearm radial artery occlusion (RAO) assessed by Doppler ultrasound at hospital discharge. The prespecified DISCOPHILE COMPLEX hand function substudy is a noninferiority trial evaluating whether large-bore DRA is not inferior to conventional TRA with respect to change in full- Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire score from baseline to 12 months in participants of the DISCO COMPLEX trial.
Enrolment status
The trial aims to recruit a total of 708 patients from 10 to 15 participating centers across Europe. The first patient was enrolled on August 31, 2023. As of August 20, 2025, 385 patients have been included.
Conclusion
DISCO COMPLEX is the first randomized clinical trial designed to test the superiority of large-bore DRA over conventional TRA in reducing RAO rates among patients undergoing complex PCI with 7-Fr guide catheters.
Trial Registration
Clinicaltrials.gov: Identifier, NCT05490238.
GRAPHICAL ABSTRACT
Fr, French; PCI, percutaneous coronary intervention.
Background
The radial artery is recommended as the standard vascular access for coronary angiography and/or percutaneous coronary intervention (PCI), irrespective of baseline clinical presentation. ,, Robust randomized data demonstrate that, compared with transfemoral access (TFA), transradial access (TRA) significantly reduces all-cause mortality, major bleeding, and vascular complications. , Additionally, TRA improves quality of life and is cost-effective, enabling early ambulation and same-day discharge for both diagnostic and interventional procedures. , In patients with complex coronary lesions, such as chronic total occlusions (CTOs), left main disease, heavily calcified lesions, or complex bifurcations, undergoing PCI with 7-French (Fr) guide catheters, large-bore TRA significantly reduces access site bleeding and vascular complications compared to TFA, without compromising procedural success.
Distal radial access (DRA) has recently emerged as an alternative to conventional TRA for coronary angiography and/or PCI. Compared to conventional TRA, DRA significantly reduces the risks of radial artery occlusion (RAO) and clinically significant hematomas, despite requiring longer cannulation and sheath insertion times, more puncture attempts, and higher crossover rates. , This advantage in RAO prevention may however be attenuated when best preventive practices are rigorously applied. Additionally, DRA with 5- or 6-Fr introducer sheaths demonstrated hand function outcomes comparable to those of conventional TRA for up to 1-year follow-up. , However, current randomized evidence on DRA primarily involves low-risk patients with chronic coronary syndromes undergoing diagnostic angiography or noncomplex PCI with ≤ 6-Fr sheaths. ,, The feasibility and safety of large-bore (≥7-Fr) DRA remain therefore uncertain due to the smaller caliber of the distal radial artery, which may increase the risks of radial artery spasm, access site crossover, and RAO. Existing data on large-bore DRA PCI are derived mainly from small observational studies or post-hoc registry analyses, which are limited by heterogeneity in patient selection, sheath and catheter sizes, study endpoints, and RAO assessment methods. ,,, To address this gap in knowledge, we designed a randomized controlled trial to evaluate the superiority of large-bore DRA versus conventional TRA for complex PCI using a 7-Fr introducer sheath with respect to the incidence of forearm RAO at hospital discharge.
Methods
Study design and organization
DISCO COMPLEX ( DIStal Versus COnventional Radial Access for COMPLEX Large-bore Percutaneous Coronary Intervention ) is an investigator-initiated, prospective, multicenter, international, open-label, randomized controlled trial with a superiority design and blinded outcome assessment. The trial compares DRA with conventional TRA using a 7-Fr introducer sheath in patients undergoing PCI for complex coronary lesions requiring large-bore guiding catheters ( Figure 1 , Graphical abstract ). The study protocol was designed by the steering committee, and all data are managed by the Department of Clinical Research, University of Bern, Switzerland. The study organization is detailed in Supplementary Table I . The steering committee is responsible for the scientific and operational conduct of the study, integrity of data analysis and reporting of results. The trial is being conducted in accordance with the Good Clinical Practice guidelines. Ethical committees at each participating site have approved the study protocol, and all patients provide informed consent before enrolment in the study. This study protocol is reported according to the 2025 CONSORT guidelines ( Supplementary Table II) . The trial is registered at www.clinicaltrials.gov ( Identifier, NCT05490238 ).
Study flowchart. CTO, chronic total occlusion; Fr, French; PCI, percutaneous coronary intervention; RAO, radial artery occlusion.
Study objectives
The primary objective of the DISCO COMPLEX trial is to demonstrate that large-bore DRA using a 7-Fr introducer sheath for complex PCI is superior to conventional TRA with respect to the occurrence of forearm RAO at hospital discharge.
Study population, enrolment, and randomization
Patients with chronic or acute coronary syndromes scheduled for PCI of complex coronary lesions, including CTOs, left main disease, heavily calcified lesions, and complex bifurcations, and who require a large bore 7-Fr guide catheter according to the operator decision, are screened for inclusion according to the study enrolment criteria ( Table 1 , Graphical abstract ). Eligible patients provide written informed consent prior to PCI and are randomized in a 1:1 ratio to DRA or TRA using a 7-Fr thin-walled introducer sheath. All study patients receive the 7-Fr Glidesheath Slender ( Terumo Corp., Tokyo, Japan ) introducer sheath to minimize confounding from the use of different introducer sheath designs that could affect primary outcome assessment, regardless of treatment allocation. Operators may choose the left or right radial artery based on clinical judgment and procedural preference. Before PCI, hand function of both patient arms is assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and the Michigan Hand Outcomes Questionnaire (MHQ). In addition, patients from selected participating centers who provide written informed consent are evaluated with dedicated motor (Pinch grip test) and sensory (Semmes-Weinstein monofilaments test) examinations. Randomization is performed centrally through an electronic data capture system in permuted block sizes of 2 or 4 patients, stratified by study center, PCI indication (CTO versus non-CTO), and participation to the prespecified hand function substudy. There is no blinding of the randomization assignment.
Table 1
Study enrolment criteria.
| Inclusion criteria |
|---|
| 1. Age ≥18 years. |
| 2. Patient presenting with chronic or acute coronary syndrome, including unstable angina or NSTEMI. |
| 3. Patient scheduled for PCI of complex coronary lesions, such as chronic total occlusions, left main disease, heavily calcified lesions, complex bifurcations, or other coronary lesions for whom the operator anticipates the need for a 7-Fr guiding catheter. |
| 4. Patient able to provide written informed consent. |
| 5. Patient willing to comply with all study protocol required evaluations. |
| Exclusion criteria |
| 1. Contraindications to TRA, such as occlusive upper arm peripheral artery disease, or known anatomic variants prohibiting TRA on both sides. |
| 2. Patient with acute STEMI. |
| 3. Patient with cardiogenic shock. |
| 4. Patient on chronic hemodialysis. |
| 5. Patient with medical conditions that may cause noncompliance with the study protocol and/or may confound the data interpretation. |
| 6. Patient unable to provide written informed consent. |
Fr, French; NSTEMI, non-ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; TRA, transradial access.
Study treatment
To ensure consistent expertise and proficiency among operators across all participating sites and randomized treatment arms, eligibility for study participation requires that operators, (1) are experienced in performing TRA PCI, including for patients with complex coronary lesions; (2) are fully independent in performing DRA; and (3) have completed a minimum of 100 DRA procedures. Randomized vascular access is performed according to standard institutional protocol. The use of Doppler ultrasound (US) to guide arterial access is left to the operator’s discretion. The need for a double arterial access for CTO-PCI is also left at the operator’s discretion, but the use of a second radial access (DRA or TRA) is strongly encouraged. Only complications attributable to the randomized access site and within-randomization cross-over access sites will be analyzed for the primary endpoint, whereas complications attributable to the additional access sites will be analyzed as a secondary endpoint.
Following placement of the radial introducer sheath, a standardized spasmolytic cocktail containing intra-arterial verapamil (± nitroglycerin) and a weight-adjusted unfractionated heparin bolus is administered to maintain an activated clotting time of 250-300 seconds throughout the procedure. Administration of glycoprotein IIb/IIIa inhibitors and/or bivalirudin is left to the operator’s discretion. Similarly, the technique for complex PCI is determined by the operator, while intracoronary imaging is strongly encouraged. The use of the Ultimaster Tansei drug-eluting stent (DES) ( Terumo Corp., Tokyo, Japan ) is mandated in all study patients, when feasible. Tansei represents the latest iteration of the Ultimaster biodegradable polymer sirolimus-eluting stent family and is specifically designed to enhance safety and efficacy during PCI of complex coronary lesions. A prespecified subanalysis of the DISCO COMPLEX trial will evaluate the safety and efficacy of the Ultimaster Tansei DES in patients undergoing complex PCI under real-world conditions. Following PCI, patients are managed according to standard institutional practices. Dual antiplatelet therapy is prescribed at the operator’s discretion in accordance with current guidelines. ,, In the TRA group, hemostasis is achieved using a closure device in accordance with the international consensus document on best practices for the prevention of RAO after transradial diagnostic angiography and intervention. Radial artery patency during hemostasis is assessed using the reverse Barbeau test. Because patent hemostasis cannot be reliably assessed by ulnar artery compression after DRA—given that the puncture site lies within the hand’s anastomotic network—and since the clinical utility of ultrasound-based patency testing remains uncertain , hemostasis in the DRA group is performed according to standard local protocols. In both the TRA and DRA groups, short hemostatic compression durations are strongly encouraged to minimize the risk of RAO.
Study treatment failure
Access site crossover is defined as any puncture of an access site other than the randomized radial access site, with or without arterial sheath insertion, either due to unsuccessful puncture or abandonment of access site after successful puncture. Definitions of access site crossovers are provided in Table 2 . Target crossover rates will be <5% for DRA to TRA, and <1% for TRA to DRA. To minimize crossover rates and preserve statistical power for the primary endpoint superiority hypothesis, within-randomization crossover ( puncture of contralateral radial artery corresponding to the same access strategy as the randomized site) is strongly encouraged. If within-randomization crossover is unsuccessful or must be abandoned after successful puncture, between-randomization crossover (puncture of the nonrandomized radial access site) is permitted. In case both within- and between-randomization radial crossovers fail or be abandoned, alternative access sites (left or right femoral, brachial, and ulnar arteries) are permitted. For the intention-to-treat (ITT) analysis, only forearm RAO events attributable to the initially randomized radial access sites (including within- and between-randomization crossovers) will be included. For the per-protocol (PP) analysis, only forearm RAO events from the randomized punctured radial access site and within-randomization crossovers will be considered. Access site complications will be assessed across all access sites combined and stratified by location (left or right) and type (TRA, DRA, femoral, brachial, or ulnar arteries) as part of secondary endpoint analyses.
Table 2
Study definitions of access site cross-overs.
| CROSS-OVERS | Randomized to DRA | Randomized to TRA | Primary endpoint forearm RAO (analyzed in all punctured DRA and TRA) |
|---|---|---|---|
| Within-randomization cross-over |
left DRA to right DRA
right DRA to left DRA |
right TRA to left TRA
left TRA to right TRA |
ITT, PP |
| Between-randomization cross-over |
left DRA to left TRA
left DRA to right TRA right DRA to left TRA right DRA to right TRA |
left TRA to left DRA
left TRA to right DRA right TRA to left DRA right TRA to right DRA |
ITT |
| Other cross-overs | left/right DRA to left/right femoral, brachial, or ulnar arteries | left/right TRA to left/right femoral, brachial, or ulnar arteries |
ITT
cross-over cannot contribute to forearm RAO |
DRA, distal radial access; ITT, intention-to-treat; PP, per-protocol; TRA, transradial access.
Study follow-up
The schedule of assessments is outlined in Figure 2 . An independent investigator (not involved in the procedure) will perform a Doppler US examination at hospital discharge to assess for RAO. This assessment will occur no earlier than 6 hours postprocedure, ideally between 8 and 48 hours. In the DRA group, both forearm and distal radial access sites will be evaluated. In cases of within-randomization access site crossover ( Table 2 ), all punctured access sites (both randomized and crossover) will be assessed for the occurrence of RAO by Doppler US. Access site bleeding will be evaluated prior to discharge according to the Early Discharge After Transradial Stenting of Coronary Arteries Study (EASY) and Bleeding Academic Research Consortium (BARC) criteria. In cases of within-randomization, between-randomization , or other access site crossovers ( Table 2 ), bleeding will be assessed separately for each punctured access site.
