Clinical trial NCT02456402: Drug Coated Balloon Compared to Bare Metal Stent for de Novo Coronary Artery Lesions
Official title: Randomized Controlled Trial of Drug Coated Balloon Compared to Bare Metal Stent Using FFR-guidance for the Treatment of de Novo Coronary Artery Lesions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stable Angina
Unstable Angina
Lead sponsor: Ulsan University Hospital
Sponsor class: OTHER
Collaborators: name: Seoul National University Hospital
First posted: 2015-05-28
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized trial will assess the efficacy of Drug Coated Balloon (DCB) compared to Bare Metal Stent (BMS) using Fractional Flow Reserve (FFR) guidance for de novo coronary artery lesions in patients unable to tolerate dual antiplatelet therapy and at high risk of bleeding. Patients will be randomized after balloon angioplasty to receive either DCB or BMS. Endpoints are late luminal loss at 9 months, and major adverse cardiac events including arterial thrombosis at 1, 9 and 12 months.

Detailed description: Although the use of drug-eluting stents (DES) has reduced in-stent restenosis when compared to bare metal stents (BMS) and decreased the incidence of adverse clinical events (1-2), DES therapy is limited by delayed arterial healing, late acquired malapposition and neo-atherosclerosis leading to an increased risk of late stent thrombosis and late restenosis (3-4). Conceptually, a permanent stent inhibits advantageous vascular remodeling and durable polymer provokes excessive inflammation (5). Non-stent based local drug delivery using paclitaxel-coated balloon has emerged as a new clinical treatment alternative by maintaining the anti-proliferative properties of DES (6). There is limited data on the efficacy of Drug Coated Balloon (DCB) treatment for de novo coronary lesions when compared to BMS. To avoid the risk of abrupt closure of target lesion after balloon angioplasty, a reliable predictor of coronary flow is necessary especially in de novo lesions of major coronary arteries. Therefore, using fractional flow reserve (FFR) after angioplasty as a good indicator of immediate functional improvement and reduced restenosis (7), the aim of this study is to assess the efficacy of DCB treatment compared to BMS in patients with de novo coronary artery lesions.

Patients with de novo coronary artery lesions with \> 50% stenosis in a single vessel and at high risk of bleeding with the inability to tolerate dual antiplatelet therapy (DAPT) will be included in this trial. Patients will undergo balloon angioplasty and if the FFR post balloon angioplasty is \> 0.80, they will be randomized to receive either DCB or BMS. Patients will receive Quantitative Coronary Angiography (QCA) analysis at 9 months follow-up. Endpoints are late luminal loss at 9 months and major adverse events including arterial thrombosis at 1, 9 and 12 months and these endpoints will be compared between DCB and BMS groups.

Eligibility criteria: Inclusion Criteria:

* Stable Angina and Unstable angina
* single de novo coronary artery lesions in a single vessel with \> 50% diameter stenosis with a reference diameter \> 2.75mm
* Patients at high risk of bleeding and whom cannot tolerate dual antiplatelet therapy for \> 1 month are inclusion criteria for the study and are listed here:
* Unexplained anemia
* Atrial fibrillation with CHADSVASC \> or equal to 1
* Patients awaiting for non cardiac surgery within a year
* History of massive hemorrhage requiring transfusion
* History of upper GI bleeding
* Malignancy
* Poor compliance with medication

Exclusion Criteria:

* STEMI/NSTEMI within the preceding 72 hours
* Multivessel disease, chronic total occlusion, long lesions and left main disease
* heart failure with ejection fraction \< 35% and/or cardiogenic shock
* Previous history of or planned coronary artery bypass grafting
* life expectancy of less than 1 year

Primary outcomes:
measure: Late luminal loss
timeFrame: 9 months
Secondary outcomes:
measure: Major adverse cardiovascular events (MACE) (death, myocardial infarction, repeat revascularization, recurrent ischemic symptoms)
timeFrame: Post procedure (up to 1 hour), 1 month, 9 months and 12 months
measure: Arterial thrombosis
timeFrame: Post procedure (up to 1 hour), 1 month, 9 months and 12 months
measure: Fractional Flow Reserve
timeFrame: Post procedure (up to 1 hour) and 9 months
Other outcomes:
Locations:
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
Study officials:
affiliation: Ulsan University Hospital
name: Eun-Seok Shin, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R; RAVEL Study Group. Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002 Jun 6;346(23):1773-80. doi: 10.1056/NEJMoa012843.
citation: Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O'Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE; SIRIUS Investigators. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003 Oct 2;349(14):1315-23. doi: 10.1056/NEJMoa035071.
citation: Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006 Jul 4;48(1):193-202. doi: 10.1016/j.jacc.2006.03.042. Epub 2006 May 5.
citation: Nakazawa G, Vorpahl M, Finn AV, Narula J, Virmani R. One step forward and two steps back with drug-eluting-stents: from preventing restenosis to causing late thrombosis and nouveau atherosclerosis. JACC Cardiovasc Imaging. 2009 May;2(5):625-8. doi: 10.1016/j.jcmg.2009.01.011. No abstract available.
citation: Unverdorben M, Kleber FX, Heuer H, Figulla HR, Vallbracht C, Leschke M, Cremers B, Hardt S, Buerke M, Ackermann H, Boxberger M, Degenhardt R, Scheller B. Treatment of small coronary arteries with a paclitaxel-coated balloon catheter in the PEPCAD I study: are lesions clinically stable from 12 to 36 months? EuroIntervention. 2013 Sep;9(5):620-8. doi: 10.4244/EIJV9I5A99.
citation: Scheller B, Speck U, Abramjuk C, Bernhardt U, Bohm M, Nickenig G. Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation. 2004 Aug 17;110(7):810-4. doi: 10.1161/01.CIR.0000138929.71660.E0. Epub 2004 Aug 9.
citation: Bech GJ, Pijls NH, De Bruyne B, Peels KH, Michels HR, Bonnier HJ, Koolen JJ. Usefulness of fractional flow reserve to predict clinical outcome after balloon angioplasty. Circulation. 1999 Feb 23;99(7):883-8. doi: 10.1161/01.cir.99.7.883.
citation: Shin ES, Lee JM, Her AY, Chung JH, Eun Lee K, Garg S, Nam CW, Doh JH, Koo BK. Prospective randomized trial of paclitaxel-coated balloon versus bare-metal stent in high bleeding risk patients with de novo coronary artery lesions. Coron Artery Dis. 2019 Sep;30(6):425-431. doi: 10.1097/MCA.0000000000000755.