Safety and Clinical Performance of the Freesolve Resorbable Magnesium Scaffold System in the Treatment of Subjects With Long de Novo Lesions

BIOTRONIK - Safety and Clinical Performance of the Drug Eluting Resorbable MAGnesium Scaffold (Freesolve) in the Treatment of Subjects With Long de Novo Lesions in Native Coronary Arteries: BIOMAG-LL

The study objective is the assessment of safety and clinical performance of Freesolve 35- and 40-mm in de novo coronary artery lesions up to 38 mm length.

In the study presented here, an extension of the Freesolve size range (35 and 40 mm scaffold length) will be investigated with the aim of assessment the safety and clinical performance of 35 and 40 mm Freesolve in de novo coronary artery lesions up to 38 mm in length to support CE certification of these sizes.

BIOMAG-LL is a pre-marketing study. It is a prospective, international, multi-center, single arm trial. The primary endpoint of the study will be Target Lesion Failure (TLF) rate at 12 months. Clinical follow-up will be conducted at 1, 6, 12, 36, and 60 months post-procedure.

The total duration of the study is approximately six and a half years, including the fifteen-month recruitment phase and the five-year follow-up period. A sample size of 100 patients is expected.

In addition, it is intended to conduct a pharmacokinetic substudy. The objective of this substudy is to describe the pharmacokinetics of sirolimus delivered by Freesolve. For this purpose, 15 patients will be prospectively enrolled in the substudy with a whole blood sample collected up to seven days after the procedure.

Inclusion Criteria:

Clinical Inclusion Criteria

1. Subject is ≥ 18 years and ≤ 80 years of age

2. Subject has provided written informed consent as approved by the Independent Ethical Committee (IEC) or Institutional Review Board (IRB) of the respective clinical site prior to the study related procedures

3. Subject is eligible for PCI according to the applicable guidelines

4. Subject is an acceptable candidate for coronary artery bypass surgery

5. Subjects with stable or unstable angina pectoris, documented silent ischemia/abnormal physiologic testing or hemodynamically stable non-ST elevation myocardial infarction (NSTEMI) patients without angiographic evidence of thrombus at target lesion

   Note: STEMI patients may be eligible for the study for treatment of selected non-culprit lesions, if:

   • Subject and target lesion(s) meet all inclusion and no exclusion criteria and consent occurs at least ≥ 72 hours after successful treatment of the culprit lesion(s) [lesion(s) causing the acute STEMI];
   • Subject is hemodynamically stable with documented declining cardiac biomarkers;
   • Target lesion(s) to be treated are not located in the culprit vessel(s) and are not culprit lesion(s)

6. Subject is eligible for Dual Antiplatelet Therapy (DAPT) with aspirin plus either clopidogrel, prasugrel, ticagrelor, cangrelor or ticlopidine

7. Documented left ventricular ejection fraction (LVEF) ≥ 30% within 6 months prior to or during the procedure (prior to enrollment)

8. Subject is willing and able to comply with protocol requirements, including completion of study visits for the duration of the study

Angiographic Inclusion Criteria

1. Subjects with a maximum of two single de novo target lesions each in separate native coronary arteries
2. Target vessel must have a reference diameter between 2.7-4.2 mm by visual estimation, which may be assisted by Quantitative Coronary Angiography (QCA) / Intravascular Ultrasound (IVUS) / Optical Coherence Tomography (OCT)
3. Target lesion must be >28 mm and ≤ 38 mm in length by operator visual estimation, which may be assisted by QCA / IVUS / OCT, and should be amenable to treatment with a single study device
4. Target lesion stenosis ≥ 50% and < 100% by operator visual estimation, which may be assisted by QCA / IVUS / OCT. Target lesion stenosis < 70% by visual estimation, should have clinical justification for treatment as per local standards.
5. Target lesion must have a Thrombolysis In Myocardial Infarction (TIMI) flow ≥1

Exclusion Criteria:

Clinical Exclusion Criteria

1. Subject is pregnant and/or breastfeeding or intends to become pregnant during the duration of the study

2. Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with STEMI < 72 hours prior to the index procedure.

   Note: Hemodynamically stable non-STEMI (NSTEMI) subjects are eligible for study enrollment.

3. Subject has undergone prior PCI within the target vessel during the last 12 months prior to the index procedure or prior PCI within a non-target vessel <72 hours prior to the index procedure (time window is defined as the time from the end of previous intervention to the start of index procedure)

4. Subject is on dialysis or with impaired renal function (serum creatinine > 2.5 mg/dL or 221 µmol/L, determined within 72 hours prior to the index procedure)

5. Subject has a known allergy to contrast medium that cannot be adequately premedicated, or any known allergy to aspirin, P2Y12 inhibitors, both heparin and bivalirudin, sirolimus (or similar limus drugs), poly L-lactide, the scaffold material (magnesium, aluminum, tantalum)

6. Subject is receiving oral or intravenous immunosuppressive therapy (inhaled steroids are permitted) or has known life-limiting immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus; diabetes mellitus is permitted)

7. Life expectancy less than 1 year

8. Planned surgery or dental surgical procedure within 6 months after index procedure, unless DAPT can be maintained.

9. In the investigator's opinion subject will not be able to comply with the follow-up requirements

10. Subjects under oral anticoagulation therapy (OAC) prior to index procedure unless DAPT + OAC (i.e. triple therapy) can be maintained for a minimum of 1 month

11. Subject has had a stroke or transient ischemic attack (TIA) within 6 months prior to the index procedure .

12. Subject with active bleeding disorder, active coagulopathy, or any other reason, who is ineligible for DAPT.

13. Subject is currently participating or plans to participate in another study with an investigational device or an investigational drug

Angiographic Exclusion Criteria:

1. Target vessel has been previously treated and the target lesion is within 5 mm proximal or distal to the previously treated lesion.
2. Left main coronary artery disease
3. Target lesion was totally occluded (100% stenosis)
4. Thrombus in target vessel
5. Future planned staged PCI either in target or non-target vessel
6. Ostial target lesion within the left descending (LAD), left circumflex (LCx), or right coronary artery (within 5.0 mm of vessel origin)
7. Target lesion involves a side branch ≥ 2.0 mm in diameter that requires a two-device strategy after pre-dilatation.
8. Target lesion is located in or supplied by an arterial or venous bypass graft.
9. Target lesion with excessive tortuosity proximal to or within the lesion based on visual estimation or heavily calcified target lesion which cannot be adequately pre-dilated by a non-compliant and/or cutting/scoring balloon as described in angiographic exclusion criteria 10.
10. The target lesion requires treatment with the device other than the non-compliant balloon and/or cutting/scoring balloon prior to scaffold placement (including but not limited to atherectomy devices, intravascular lithotripsy, drug-coated balloons etc.)
11. Target vessel was treated with brachytherapy any time prior to the index procedure.
12. Unsuccessful pre-dilatation, defined as residual stenosis > 20% (by visual estimation) and / or angiographic complications (e.g. distal embolization, side branch closure, flow-limiting dissections)