Hybrid PCI using a magnesium bioresorbable scaffold plus drug-coated balloons versus drug-eluting stents for long, diffuse coronary artery disease

Hybrid Percutaneous Coronary Intervention Combining a Bioresorbable Scaffold With Drug-coated Balloons Versus a Conventional Drug-eluting Stent-based Strategy in Patients With Long and Diffuse Coronary Artery Disease: the BIOHYBRID Randomized Pilot Trial

It will test whether combining a magnesium bioresorbable scaffold with paclitaxel drug-coated balloons works as well as newer drug-eluting stents for people with long or diffuse coronary artery blockages who need PCI.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Geneva (Academic / other)
• Locations: 1 site (Geneva, Canton of Geneva)
• Trial ID: NCT06710210 on ClinicalTrials.gov

What this trial studies

This interventional trial compares a hybrid PCI approach using a magnesium-based sirolimus-eluting bioresorbable scaffold (Freesolve) plus paclitaxel-coated drug-coated balloons (Pantera Lux) against a conventional newer-generation drug-eluting stent strategy (Orsiro Mission) in patients with long and/or diffuse coronary lesions. Participants receive one of the two PCI strategies and undergo non-invasive angiography-derived fractional flow reserve (FFRangio) measurement immediately after the index procedure and again at 12 months. The primary endpoint is the vessel-level absolute change in FFRangio between post-procedure and 12-month follow-up, with additional safety and clinical outcomes tracked over follow-up. The trial is conducted at Geneva University Hospitals with standardized imaging and clinical follow-up procedures.

Who should consider this trial

Good fit: Adults (≥18) with long or diffuse coronary artery lesions suitable for PCI who are hemodynamically stable and have chronic coronary syndrome, unstable angina, NSTEMI, or stabilized STEMI non-culprit lesions, and who can provide informed consent.

Not a fit: Patients with short, focal coronary lesions, hemodynamic instability, STEMI culprit lesions, or contraindications to the study devices or required antiplatelet therapy are unlikely to benefit from this specific hybrid approach.

Why it matters

Potential benefit: If successful, the hybrid approach could preserve vessel function and reduce long-term stent-related complications while achieving similar or better improvement in blood flow.

How similar studies have performed: Prior studies of bioresorbable scaffolds and drug-coated balloons have shown promising results in some settings but mixed outcomes overall, and hybrid strategies for long and diffuse lesions remain relatively novel with limited large-scale evidence.

Eligibility criteria

Inclusion criteria:

* Clinical inclusion criteria

  1. Participant is ≥18 years.
  2. Participant has provided written informed consent as approved by the independent Ethical Committee (EC) or Institutional Review Board (IRB) of the respective participating centre prior to any study-related procedure.
  3. Participant is eligible for PCI according to the ESC guidelines (4, 5) .
  4. Participant is hemodynamically stable.
  5. Participant with chronic coronary syndrome (CCS) or acute coronary syndrome (ACS): unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), or stabilized ST-segment elevation myocardial infarction (STEMI).

  5a. Participants with STEMI are eligible for the treatment of non-culprit coronary lesions, if participant consent occurs ≥72 hours after successful primary PCI of the culprit STEMI lesion.

  5b. Target lesion(s) to be treated are not located in the STEMI culprit vessel(s) and are not STEMI culprit lesion(s).

  6\. Participant is eligible for dual antiplatelet therapy (DAPT) with aspirin plus either clopidogrel, prasugrel, or ticagrelor for ≥6 months.

  7\. Participant is willing to participate and able to comply with the protocol requirements for the duration of the study, including completion of study visits and control coronary angiogram at 12 months.

Angiographic inclusion criteria 8. Target lesion length is \>40 mm according to operator visual estimation, which may be assisted by Quantitative Coronary Angiography (QCA), Intravascular Ultrasound (IVUS), or Optical Coherence Tomography (OCT).

9\. Target vessel has a maximum reference diameter between 3.0-4.6 mm according to operator visual estimation, which may be assisted by QCA, IVUS, or OCT.

Notes: The proximal segment, which has a larger vessel diameter, will be treated with one Freesolve scaffold, in accordance with the vessel diameter range specified in the IFU. The distal segment, which naturally tapers to a smaller diameter, can be treated with one or more Pantera Lux DCB, in accordance with the vessel diameter range specified in the IFU.

10\. Target lesion with a baseline (pre-PCI) Thrombolysis In Myocardial Infarction (TIMI) flow ≥1.

Exclusion criteria:

Clinical exclusion criteria

1. Participant has a known allergy to contrast medium that cannot be adequately premedicated, or any known allergy or intolerance to aspirin, P2Y12 receptor inhibitors (clopidogrel, ticagrelor, or prasugrel), both heparin and bivalirudin, any of the following DES or bioresorbable scaffold component (magnesium, aluminium, tantalum, poly-L-lactide, or sirolimus), or drug-coated balloon component (paclitaxel).
2. Participant with STEMI \<72 hours prior to study index procedure. 12a: Participants with hemodynamically stable NSTEMI are eligible for study enrolment.
3. Participant with prior PCI within the target vessel during the last 12 months prior to the study index procedure.
4. Participant is on dialysis or has chronically impaired renal function defined as serum creatinine \>2.5 mg/dL or 221 μmol/L.
5. Participant is unable to adhere to DAPT for at least 6 months (e.g. planned surgery, dental surgical procedure, active bleeding disorders, active coagulopathy).
6. Participant is on oral anticoagulation therapy (OAC) prior to index procedure unless DAPT plus OAC (i.e. triple therapy) can be maintained for a minimum of 1 month.
7. Participant with life expectancy \<1 year.
8. Participant is pregnant and/or breastfeeding or intends to become pregnant during the duration of the study.
9. Participant is currently participating or planning to participate in another interventional clinical trial, except for observational registries or previous enrolment into the current investigation.
10. Participant unwilling or unable (e.g. physical or cognitive) to comply with study procedures, medication adherence and schedule.
11. Contraindications and limitations of the medical devices as described in the instructions for use.
12. Known or suspected non-compliance, drug or alcohol abuse.
13. Inability to follow the procedures of the investigation, e.g. due to language problems, psychological disorders, dementia, etc. of the participant.
14. Participation in another investigation with an investigational drug or another MD within the 30 days preceding and during the present investigation.

    Angiographic exclusion criteria
15. Target vessel previously treated with a bare-metal stent or a drug-eluting stent and the target lesion is within 5 mm proximal or distal to the previously treated lesion.
16. Target lesion is a chronic total occlusion.
17. Target lesion is located in left main coronary artery, ostial left anterior descending artery, ostial left circumflex artery, or ostial right coronary artery (within 5.0 mm of the vessel origin).
18. Target lesion is located in, or supplied by, an arterial or venous bypass graft.
19. Target lesion with excessive tortuosity proximal to or within the lesion based on operator visual estimation, or heavily calcified target lesion which may be adequately prepared using a non-compliant and/or cutting/scoring balloon.
20. Target lesion requires treatment with a device other than a non-compliant balloon and/or a modified (cutting/scoring) balloon prior to scaffold/stent placement (including but not limited to atherectomy devices, intravascular lithotripsy).
21. Target lesion involves a coronary bifurcation with a side branch with reference vessel diameter ≥2.0 mm that requires a two-device strategy after pre-dilatation.
22. Presence of thrombus in the target vessel.
23. Future planned staged PCI or coronary artery bypass graft surgery after the study PCI procedure.
24. Target with unsuccessful lesion preparation, defined as the absence of residual stenosis ≥30%, TIMI flow grade \<3 following complete lesion preparation (6), type C to F coronary artery dissection according to the National Heart, Lung and Blood Institute (NHLBI) classification (7) (Appendix 2) and angiographic complications (e.g. distal embolization, or side branch closure).

Where this trial is running

Geneva, Canton of Geneva

• Geneva University Hospitals — Geneva, Canton of Geneva, Switzerland (Recruiting)

Study contacts

• Study coordinator: Juan F Iglesias, Principal Investigator

Conditions Coronary Artery Disease; Diffuse Coronary Artery Disease; Percutaneous Coronary Intervention; Diffuse/long coronary artery disease; Percutaneous coronary intervention; Drug-eluting stents; Drug-coated balloons; Bioresorbable scaffold