SPAGO: Sirolimus Paclitaxel Angiographic Gain Objective

Official title

Selution Sirolimus Coated Balloon (MedAlliance) Versus SeQuent Please Neo Paclitaxel Coated Balloon (Bbraun) for the Treatment of de Novo Coronary Artery Lesions in Medium-small Size Vessels.

Overview

The objective of the study is to compare angiographic outcomes of Selution sirolimus coated balloon (MedAlliance) versus SeQuent Please Neo paclitaxel coated balloon (Bbraun) for the treatment of de novo coronary artery lesions in medium size vessels (\>2.00 mm and ≤3.00 mm) with respect to Net Gain (mm) and Fractional Flow Reserve (FFR) at 12 months follow-up.

Detailed description

This is a prospective, randomized, multicenter, no-profit and post-market study in subjects with small vessels, i.e. at least one de novo lesion in a small vessel (\>2.00 mm and ≤3.00). Vessel size is evaluated by visual estimation. It is possible to include only one study lesion per patient. For the purposes of this study, in cases of diffuse coronary artery disease where overlapped DCB are utilized for the treatment of the lesion, this will be considered as a single lesion. In case of a successful predilatation (i.e. no major (type D, E, F) angiographic dissections, residual stenosis ≤ 30% and TIMI flow = 3), the subject will be randomized in a 1:1 fashion to SelutionTM or SeQuent Please NeoTM. Randomization will be stratified according to DCB length (\< 30 mm or ≥ 30 mm) in order to include at least 100 patients treated with DCB of 30 mm or longer. Measurements of intramyocardial resistances, after lesion preparation prior to DCB treatment and after DCB treatment (2 measurements), will be limited to a maximum of 100 lesions treated with DCB ≥ 30 mm. Given the lack of literature data on intramyocardial resistance measurements, a minimum of 100 subjects is considered necessary to provide an initial evaluation of these parameters. With a total sample size of 140 patients for the study, it will be allowed to enroll up to 40 patients treated with DCB \< 30 mm. Once this limit is reached, only patients treated with DCB ≥ 30 mm will be enrolled while maintaining a 1:1 randomization ratio. During the index procedure, it is possible to treat other not study lesions (if applicable) with any other commercial device (e.g. drug-eluting stent) if they are located in a different epicardial territory than the study target lesion. All not studylesions should be treated prior to study target lesion procedure, and should be successful and uncomplicated.

Follow-up by phone call will occur at 1 and 6 months post-PCI. At 12 months all subjects will perform an angiographic follow up at the same site where the index procedure was performed. Quantitative Coronary Angiography (QCA) assessment will be performed at baseline (pre- and post-procedure) and on follow up angiography by the imaging core lab. FFR assessment will be performed at the time of follow-up angiography.

All subjects must receive dual anti-platelet therapy (DAPT), being aspirin (ASA) and P2Y12 inhibition therapy for at least 1 month after drug coated balloon PCI or according to standard local practice (with the choice of agent left to the discretion of the investigator), followed by ASA monotherapy indefinitely. However, in case the subject had recent ACS or is receiving additional drug-eluting stents, DAPT must be given according to local standard of care.

Interventions

• Device sirolimus-eluting balloon (Selution)
  PCI treatment with DCB, in particular sirolimus coated balloon
• Device paclitaxel-eluting balloon (SeQuent Please Neo)
  PCI treatment with DCB, in particular paclitaxel coated balloon

Primary outcome measures

• In-segment (balloon treated area) Net Gain (mm) at 12 months post-procedure [Time frame: 12 months post-procedure]
• Fractional Flow Reserve (FFR) [Time frame: From enrollment to the end of treatment at 12 months]

Secondary outcome measures (12)

• Device success (lesion based) [Time frame: 12 months post-procedure]
• Procedure success [Time frame: 12 months post-procedure]
• Angiographic outcomes 1 [Time frame: 12 months post-procedure]
• Angiographic outcomes 2 [Time frame: 12 months post-procedure]
• Angiographic outcomes 3 [Time frame: 12 months post-procedure]
• Angiographic outcomes 4 [Time frame: 12 months post-procedure]
• Device oriented Composite Endpoint (DoCE/ TLF) [Time frame: 12 months post-procedure]
• Acute/subacute/early/late vessel thrombosis [Time frame: 12 months post-procedure]
• Periprocedural myocardial infarction [Time frame: From enrollment to the end of treatment at 12 months]
• PCI related myocardial injury [Time frame: From enrollment to the end of treatment at 12 months]
• Absolute difference in CFR for the first 100 patients treated with DCB ≥ 30 mm [Time frame: baseline]
• Absolute variation in IMR for the first 100 patients treated with DCB ≥ 30 mm [Time frame: baseline]

Eligibility criteria

Inclusion criteria

• Male or female subjects ≥18 years
• Subject with chronic stable angina or stabilized acute coronary syndromes with normal cardiac biomarker values.
• The subject has at least one de-novo lesion in a small vessel (>2.00 mm and ≤3.00 mm prior to pre-dilatation) with a diameter stenosis between 50% and 99% (prior to pre-dilatation). It is possible to enroll subjects that have a stent previously implanted in the same epicardial territory (main vessel and ramifications) of the target lesion
• Patients with target lesion to be treated with DCB < 30 mm in length (up to 40 patients) or with DCB ≥ 30 mm in length (at least 100 patients)
• Able to understand and provide informed consent and comply with all study procedures including 12 months angiographic follow-up
• Subject must have completed the follow-up phase of any previous study

Exclusion criteria

• Subject is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential)
• Evidence of ongoing acute myocardial infarction (AMI) in ECG and/or elevated cardiac biomarkers (according to local standard hospital practice) have not returned within normal limits at the time of procedure
• Known contraindication or hypersensitivity to sirolimus, paclitaxel, or to medications such as aspirin, heparin, and all of the following four medications: clopidogrel bisulfate, ticlopidine, prasugrel, ticagrelor
• Subjects who experienced a previous PCI with DCB in the epicardial territory (main vessel and ramifications) where the target lesion is located, during the last 12 months
• Subject suffered from stroke/TIA during the last 6 months
• LVEF <30%
• Platelet count <100,000 cells/mm3 or >400,000 cells/mm3, a WBC of <3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis)
• Known renal insufficiency (e.g. serum creatinine >2,5 mg/dL, creatinine clearance ≤30 mL/min or eGFR ≤30 mL/min/m2), or subject on dialysis, or acute kidney failure (as per physician judgment)
• Subject undergoing planned surgery within 1 month with the necessity to stop DAPT
• History of bleeding diathesis or coagulopathy
• The subject is a recipient of a heart transplant
• Concurrent medical condition with a life expectancy of less than 12 months
• The subject is unwilling/not able to return for angiographic re-catheterisation at 12 months follow-up
• Currently participating in another trial

Angiographic exclusion criteria:

• Target vessel size >3.00 mm
• Target vessel size ≤2.00 mm
• Target lesion has a diameter stenosis < 50% prior to pre-dilatation
• Target lesion has a total occlusion or TIMI flow < 2 prior to pre-dilatation
• Pre-dilatation of the target lesion not performed or not successful (residual stenosis > 30%, TIMI flow < 3 and presence of major angiographic dissections)
• Target lesion in left main stem
• The target vessel contains visible thrombus
• Aorto-ostial target lesion (within 3 mm of the aorta junction)
• Lesion is located within an arterial or saphenous vein graft or distal to a diseased arterial or saphenous vein graft

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 10 centers

• Clinica Montevergine — Mercogliano
• ASST Papa Giovanni XXIII — Bergamo
• Fondazione Poliambulanza — Brescia
• Azienda Ospedaliero Universitaria di Ferrara — Ferrara
• Centro Cardiologico Monzino — Milan
• Istituto Clinico Humanitas — Rozzano
• Clinica Mediterranea — Naples
• Azienda Ospedaliero Universitaria San Luigi Gonzaga — Orbassano
• … and 2 more centers

Publications

• Duan Y, Wang Y, Zhang M, Li Z, Chen L, Miao H, Pei S, Lu Y, Wang Z. Computational Pressure-Fluid Dynamics Applied to Index of Microcirculatory Resistance, Predicting the Prognosis of Drug-Coated Balloons Compared With Drug-Eluting Stents in STEMI Patients. Front Physiol. 2022 May 24;13:898659. doi: 10.3389/fphys.2022.898659. eCollection 2022. PMID 35685283
• Nishi T, Murai T, Ciccarelli G, Shah SV, Kobayashi Y, Derimay F, Waseda K, Moonen A, Hoshino M, Hirohata A, Yong ASC, Ng MKC, Amano T, Barbato E, Kakuta T, Fearon WF. Prognostic Value of Coronary Microvascular Function Measured Immediately After Percutaneous Coronary Intervention in Stable Coronary Artery Disease: An International Multicenter Study. Circ Cardiovasc Interv. 2019 Sep;12(9):e007889. PMID 31525096
• Fearon WF, Balsam LB, Farouque HM, Caffarelli AD, Robbins RC, Fitzgerald PJ, Yock PG, Yeung AC. Novel index for invasively assessing the coronary microcirculation. Circulation. 2003 Jul 1;107(25):3129-32. doi: 10.1161/01.CIR.0000080700.98607.D1. Epub 2003 Jun 23. PMID 12821539
• Del Buono MG, Montone RA, Camilli M, Carbone S, Narula J, Lavie CJ, Niccoli G, Crea F. Coronary Microvascular Dysfunction Across the Spectrum of Cardiovascular Diseases: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Sep 28;78(13):1352-1371. doi: 10.1016/j.jacc.2021.07.042. PMID 34556322
• Colleran R, Harada Y, Kufner S, Giacoppo D, Joner M, Cassese S, Ibrahim T, Laugwitz KL, Kastrati A, Byrne RA. Changes in high-sensitivity troponin after drug-coated balloon angioplasty for drug-eluting stent restenosis. EuroIntervention. 2017 Oct 20;13(8):962-969. doi: 10.4244/EIJ-D-16-00939. PMID 28134126
• Ikenaga H, Kurisu S, Ishibashi K, Dohi Y, Fukuda Y, Kihara Y. Slow-flow phenomenon after Paclitaxel-coated balloon angioplasty: findings from optical coherence tomography and coronary angioscopy. JACC Cardiovasc Interv. 2015 Apr 20;8(4):e59-62. doi: 10.1016/j.jcin.2014.11.016. Epub 2015 Mar 26. No abstract available. PMID 25819189
• Young M, Cuculi F, Erne P. PTCA with drug-coated balloons is associated with immediate decrease of coronary flow reserve. Catheter Cardiovasc Interv. 2013 Mar;81(4):682-6. doi: 10.1002/ccd.23502. Epub 2013 Jan 29. PMID 23361864
• Aihara K, Torii S, Ito M, Koseki K, Shiozaki M, Sato Y, Nakamura N, Yoshikawa A, Ikari Y, Nakazawa G. Biological differences of three paclitaxel- and sirolimus-coated balloons on coronary lesions in a rabbit model. EuroIntervention. 2024 Mar 18;20(6):e389-e398. doi: 10.4244/EIJ-D-23-00425. PMID 38506736

Identifiers

NCT: NCT06373601 · SPAGO

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗