Bifurcation PCI With a Hybrid Strategy With Drug Eluting Balloons Versus a Stepwise Provisional Two-stent Strategy (Hybrid DEB)

Bifurcation PCI With a Hybrid Strategy With Drug Eluting Balloons Versus a Stepwise Provisional Two-stent Strategy. A Randomized Controlled Trial and Registry

The optimal treatment of coronary bifurcation lesions is complex and remains subject of current research. There is ongoing debate about the optimal strategy for bifurcations with upfront two-stent strategy or provisional one-stent strategy. Current European Society of Cardiology (ESC) guidelines advise a provisional approach with optional stepwise two-stent strategy in case of suboptimal result of the side branch (SB). However, a two-stent strategy (either upfront and stepwise) caries technical difficulties and is associated with increased procedure duration and costs and higher exposure of the patient to radiation and contrast. Therefore there is upcoming interest in the use of a drug-eluting balloon (DEB) in the side branch of bifurcation lesions after provisional approach. Drug-eluting balloons are conventional semi-compliant angioplasty balloons covered with an anti-proliferating drug, which is released into the vessel wall during inflation.

Several small pilot studies have successfully investigated a hybrid approach with use of DEB in addition to the provisional strategy. This hybrid approach has shown to be safe and feasible, however no large trials have been performed comparing this with current two-stent bifurcation strategies.

The aim of this randomized controlled, single blinded, multicenter trial is to investigate whether a hybrid DEB approach is non-inferior to a stepwise provisional two-stent strategy in patients with de novo bifurcation lesions and a suboptimal result of the SB after provisional approach.

Patients included in this study will receive PCI using provisional approach (implantation of drug-eluting stent (DES) in the main branch). Patients with an unsatisfactory result of the SB after provisional PCI (≥ 70% residual stenosis and/or diminished flow < Thrombolysis in Myocardial Infarction (TIMI) III) will be randomized in a 1:1 ratio to receive the Hybrid DEB approach or the two-stent strategy. Patients with a satisfactory result of the side branch after provisional PCI will be included in a registry.

Follow-up will be performed at 12 months and at the anticipated median 2 year follow-up with a minimum follow-up of 1 year in each subject by either a phone call or outpatient clinic visit. During follow-up information regarding cardiovascular drug use, hospitalizations, invasive and non-invasive diagnostic tests, angina status and SAE's is obtained.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Coronary Bifurcation Lesion
• Intervention / Treatment: Other: Hybrid DEB approach with drug-eluting balloon; Other: Two-stent strategy

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Koen Teeuwen, MD, PhD; Phone Number: 040- 2398360; Email: koen.teeuwen@catharinaziekenhuis.nl

Study Locations

• Netherlands
  • North- Brabant
    • Eindhoven, North- Brabant, Netherlands, 5623 EJ
      • Recruiting
      • Catharina hospital
      • Contact: Koen Teeuwen, MD, PhD; Phone Number: 040-2398360
      • Contact: Daimy Dillen, MD; Phone Number: 040-2398360

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Significant de novo bifurcation lesion (main vessel and side branch diameter ≥ 2.5mm, diameter stenosis of the main vessel ≥ 70% and of the side branch ≥ 50% or in intermediate stenosis FFR ≤ 0.80 or iFR ≤ 0.89)
• Stable coronary artery disease or stabilized acute coronary syndrome
• Age ≥ 18 years
• Acceptable candidate for treatment with a drug eluting stent

Exclusion Criteria:

• Unstable clinical condition
• Previous PCI with stent implantation in the target lesion(s)
• Known comorbidity with a life expectancy of <2 year
• Active bleeding requiring medical attentions (BARC >2 at index PCI)
• Pregnancy
• Unable to provide consent for any other reason
• Participation in another stent or drug trial
• Known hypersensitivity or allergy for asprin, clopidogrel, ticagrelor, prasugrel, cobalt chromium, sirolimus, to excipients with phospholipid or related origins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Hybrid DEB; Patients randomized to hybrid DEB group will receive application of DEB in the side branch.	Other: Hybrid DEB approach with drug-eluting balloon; If a patient is randomized to the hybrid DEB approach, lesion preparation of the SB with non-compliant balloon (NC) is mandatory before DEB application. The application of DEB can be performed if acceptable result of the lesion preparation is obtained (at least TIMI III flow and no flow limiting dissection). The drug- eluting balloon used in this study is the CE- marked Magic Touch Sirolimus Coated Balloon Catheter (Concept Medical, Gujarat, India). The size of the DEB is measured on a ratio 1:1 on reference diameter of the SB. The DEB balloon is inflated for 60 seconds, or two times more than 30 seconds if long duration inflations are not possible. Finally low pressure kissing inflation with the same DEB in place, and Proximal Optimization Therapy (POT) are performed. In case of SB occlusion, or flow limiting dissections in non-Left Main (LM) bifurcations and < TIMI 3 flow or 70-99% residual stenosis in LM bifurcations, cross- over to two-stent technique is performed.
Other: Two-stent strategy; Patients randomized to two-stent strategy will receive implantation of a second DES in the side branch, using Culotte or TAP/T technique.	Other: Two-stent strategy; When randomized to the conventional two-stent strategy, TAP/T or Culotte stenting is performed. First lesion preparation of the SB is mandatory. The drug-eluting stent (Supraflex stent) can be placed in the SB if acceptable result of the lesion preparation is obtained and is measured on a 1:1 ratio on reference diameter of the SB. Finally, kissing inflation and POT are mandatory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of all-cause death, periprocedural or spontaneous myocardial infarction (MI) and/or target vessel revascularization (TVR)	Composite of all-cause death, periprocedural (according to the SCAI/ARC II definition and a secondary analysis according to the 4th universal definition) or spontaneous (according to the 4th universal definition) myocardial infarction (MI) and/or target vessel revascularization (TVR) at the anticipated median 2 year	Anticipated median 2 year follow-up after the date of randomization, with a minimum follow-up in all subjects of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major bleeding, defined as BARC type 2-5	Major bleeding, defined as BARC type 2-5 at discharge	Discharge after the PCI
Contrast volume used during the PCI procedure	Contrast volume used during the PCI procedure (in ml)	The end of the PCI
Radiation exposure of the patient, measured in DAP and AirKerma	Radiation exposure of the patient, measured in DAP and AirKerma during the PCI procedure	The end of the PCI
Procedural time, measured in minutes, defined as time from first to last procedural angiography image	Procedural time, measured in minutes, defined as time from first to last procedural angiography image	The end of the PCI
Total procedural costs (in euro's) per patient stratified to treatment group	Total procedural costs (in euro's) per patient stratified to treatment group	The end of the PCI
Percentage of stent expansion in proximal and distal main branch and side branch, measured with intracoronary imaging (OCT or IVUS)	Percentage of stent expansion in proximal and distal main branch and side branch, measured with intracoronary imaging (OCT or IVUS)	The end of the PCI
Final minimal lumen and stent area post stenting in the proximal and distal main branch measured with intracoronary imaging (OCT or IVUS)	Final minimal lumen and stent area post stenting in the proximal and distal main branch measured with intracoronary imaging (OCT or IVUS)	The end of the PCI
Dissections in the proximal and distal main branch and side branch, measured using intracoronary imaging (OCT or IVUS)	Dissections in the proximal and distal main branch and side branch, measured using intracoronary imaging (OCT or IVUS)	The end of the PCI
Core Lab Assessed initial TIMI flow main branch and side branch	Core Lab Assessed initial TIMI flow main branch and side branch	During the Coronary Angiography (CAG), before the PCI
Core Lab Assessed Lesion Length (in mm)	Core Lab Assessed Lesion Length (in mm)	During the CAG, before the PCI
Core Lab Assessed percentage diameter stenosis main branch and side branch	Core Lab Assessed percentage diameter stenosis main branch and side branch	During the CAG, before the PCI
Core Lab Assessed reference diameter (in mm) proximal main branch and side branch	Core Lab Assessed reference diameter (in mm) proximal main branch and side branch	During the CAG, before the PCI
Core Lab Assessed minimal lumen diameter (in mm) main branch and side branch	Core Lab Assessed minimal lumen diameter (in mm) main branch and side branch	During the CAG, before the PCI
The severity of calcification main branch and side branch, Core Lab Assessed	The severity of calcification main branch and side branch, Core Lab Assessed	During the CAG, before the PCI
Core Lab Assessed Bifurcation angle	Core Lab Assessed Bifurcation angle	During the CAG, before the PCI
Core Lab Assessed syntax I score as absolute value	Core Lab Assessed syntax I score as absolute value	During the CAG, before the PCI
Bifurcation medina score	Bifurcation medina score	During the CAG, before the PCI
Core Lab Assessed final TIMI flow main branch and side branch	Core Lab Assessed final TIMI flow main branch and side branch	The end of the PCI
Core Lab Assessed residual dissection (type A-F) after PCI in the main branch and/or side branch	Core Lab Assessed residual dissection (type A-F) after PCI in the main branch and/or side branch	The end of the PCI
Core Lab Assessed residual in-stent and in-segment stenosis (in %) after PCI	Core Lab Assessed residual in-stent and in-segment stenosis (in %) after PCI	The end of the PCI
Core Lab Assessed minimal lumen diameter (in mm) main branch and side branch post PCI	Core Lab Assessed minimal lumen diameter (in mm) main branch and side branch post PCI	The end of the PCI
Core Lab Assessed percentage diameter stenosis main branch and side branch post PCI	Core Lab Assessed percentage diameter stenosis main branch and side branch post PCI	The end of the PCI
Core Lab Assessed acute lumen gain (in mm) main of the branch and side branch after PCI	Core Lab Assessed acute lumen gain (in mm) main of the branch and side branch after PCI	The end of the PCI
Core Lab Assessed Procedural coronary thrombus	Core Lab Assessed Procedural coronary thrombus, defined as yes or no	The end of the PCI
Procedural success	Procedural success defined as successful stent delivery with final core lab (defined as TIMI flow of III, angiographic in-stent MB and SB diameter stenosis ≤30%, or ≤50% after DEB in the side branch) and absence of in-hospital major adverse cardiac and cerebrovascular events (MACCE, defined as all cause death, spontaneous MI, TVR, stoke) at discharge, 12 months and the anticipated median 2 year	Discharge, 12 months and the anticipated median 2 year follow-up after the date of randomization
Target vessel failure (TVF)	Target vessel failure (TVF), defined as cardiac death, target vessel spontaneous MI, TVR at discharge, 12 months and the anticipated median 2 year	Discharge, 12 months and the anticipated median 2 year follow-up after the date of randomization
Major adverse cardiac events (MACE)	Major adverse cardiac events (MACE), defined as all-cause death, spontaneous MI, repeat revascularization at discharge, 12 months and the anticipated median 2 year	Discharge, 12 months and the anticipated median 2 year follow-up after the date of randomization
Individual components of MACE and TVF	Individual components of MACE and TVF (All-cause death, cardiac death, periprocedural of spontaneous MI, target vessel revascularization, target vessel spontaneous MI) at discharge, 12 months and the anticipated median 2 year	Discharge, 12 months and the anticipated median 2 year follow-up after the date of randomization
Periprocedural MI	Periprocedural MI within 48 hours after procedure, according to the SCAI/ARC II definition, secondary analysis according to the 4th universal definition	48 hours after the Percutaneous Coronary Intervention (PCI)
Major intraprocedural complications	Major intraprocedural complications, defined as type C-F dissections, perforations, slow flow or no reflow (< TIMI III), thrombus, major side branch occlusion (>2mm) during the index procedure	The end of the PCI
Probable and definite stent thrombosis	Probable and definite stent thrombosis, defined as Angiographic confirmation of stent thrombosis, or any myocardial infarction that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause at discharge, 12 months and the anticipated median 2 year	Discharge, 12 months and the anticipated median 2 year follow-up after the date of randomization

Collaborators and Investigators

• Sponsor: Cathreine BV
• Collaborators: Catharina Ziekenhuis Eindhoven; St. Antonius Hospital; Medical Centre Leeuwarden; Albert Schweitzer Hospital; Rijnstate Hospital; VieCuri Medical Centre; Maasstad Hospital; Onze Lieve Vrouwe Gasthuis; Haga Hospital; Jeroen Bosch Ziekenhuis; Meander Medical Center; The Elisabeth-TweeSteden Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: January 25, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 16, 2023

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Coronary artery disease; Percutaneous coronary intervention; Coronary bifurcation lesion; Drug-eluting balloon
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 21112022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No