Study Rationale
Stent failure, ISR and TLF remain a significant challenge when considering percutaneous treatment options for de novo CAD in patients with diabetes mellitus. The use of combination treatment with both DCB and DES in this population has not been studied. This study aims to compare the safety and efficacy of a novel combination revascularisation strategy to DCB or DES alone in patients with de novo CAD and diabetes mellitus, a patient group that is at increased risk of TLF compared to patients who do not have diabetes mellitus.
Study Objective
To investigate the efficacy and safety of combination treatment for patients with diabetes mellitus and de novo obstructive CAD undergoing PCI consisting of angioplasty with DCB combined with DES in comparison to single device treatments with either DES or DCB alone, in a randomised, multicentric clinical trial.
Study Design
DUBSTENT-DIABETES is a prospective, randomized, multicentre, assessor-blind, investigator-initiated clinical trial. To investigate the safety and efficacy of combination treatment for patients with de novo CAD undergoing PCI. Consisting of angioplasty with DCB combined with stenting with DES in comparison to single device treatments with either DES or DCB alone.
The study will enrol 120 patients who will be randomized in a 1:1:1 fashion to receive Pantera® Lux® DCB in combination with Orsiro® DES (investigational strategy), or Pantera® Lux® DCB alone, or Orsiro® DES alone (standard of care arm). Subjects will be prospectively enrolled at 4 sites in the Republic of Ireland. In the Pantera® Lux® DCB alone comparator arm, bailout stenting will be allowed under certain criteria. The criteria for bailout stenting will be NHLBI dissection class D to F, and class C at the discretion of the operator. The Freesolveᵀᴹ resorbable magnesium scaffold should be used for bailout stenting to facilitate a leave nothing behind strategy for this comparator arm.
Patients will be screened according to the study inclusion and exclusion criteria (section) prior to coronary angiography. Patients with diabetes mellitus, planned for PCI for de novo obstructive CAD will be eligible. Baseline QCA will be performed to screen patients according to the angiographic inclusion criteria. Subjects who meet all of the study inclusion and exclusion criteria will be eligible for randomisation. Included subjects will then be randomised to either the investigational arm of combination treatment (DCB and DES treatment), or to the comparator arms of DCB treatment, or DES treatment (standard of care arm). Subjects will then receive treatment according to the randomisation.
All procedures will be performed by fully trained operators with several years of interventional experience. All procedures will be performed according to current guidelines and international standards using the Pantera® Lux® DCB and/or the Orsiro® DES. In all patients intravascular imaging is encouraged, but not mandated in the protocol. A pre-specified sub study will take place for 30 subjects who will receive optimal coherence tomography (OCT) imaging.
Baseline characteristics, vital signs, concomitant diseases, cardiovascular risk factors, medication, routine laboratory analyses, ECG data, QCA images and procedural data including periprocedural complications, and follow-up data will be collected.
All included subjects will undergo protocol mandated QCA at 6-months. The primary endpoint of the study, in-segment DS will be assessed by QCA at 6-months follow-up. Key secondary endpoints include TLF, the individual components of TLF (cardiovascular death, non-fatal MI related to the target vessel and unplanned ischaemia-driven TLR). Secondary endpoints will be assessed at 30 days, 6 months and annually up to 5 years. All angiographic endpoints including the primary endpoint will be analysed at Imaging Core Laboratory CVRI Dublin. All clinical events will be adjudicated upon by an independent CEC. The study will be conducted in accordance with the investigation plan, the current version of the Declaration of Helsinki, and national legal and regulatory requirements (2013) (15).
Study Duration
This study will enrol 120 patients in up to 4 investigative centres in the Republic of Ireland over a period of 12 months. Subjects will have follow up QCA performed 6 months after the index QCA. In-person or telephone follow-up appointments will take place at 1 year, then annually up to 5 years after the index procedure. The expected duration of the study is approximately 78 months. This consists of 12 months enrolment followed by 5 years follow up of participants from the time of enrolment of the final participant. An additional 6 months will be permitted for data freeze and statistical analysis.
