SiroMax sirolimus-coated balloon for small coronary vessels with or without prior stents

Inclusion Criteria:

* Age ≥ 21 years
* Provided written informed consent
* If a woman of child-bearing potential, agrees to use a reliable method of contraception from the time of screening through 12 months after the index procedure
* Diagnosed with symptomatic ischemic heart disease, stable or unstable angina with signs of ischemia, silent ischemia, or a positive function test
* Eligible for percutaneous coronary intervention (PCI)
* Able to tolerate dual antiplatelet therapy with aspirin, plus either Clopidogrel, Prasugrel, or Ticagrelor
* Any non-target lesions to be treated during the index procedure have been successfully treated
* Meets the additional Inclusion criteria for the corresponding arm
* Target lesion \> 50% and \< 100% stenosed by QCA in symptomatic patients, and \> 70% and \< 100% stenosed in asymptomatic patients prior to lesion pre-treatment
* Distal TIMI grade flow of 3
* Target lesion must be ≤ 26mm length
* Successful pre-treatment of the target lesion
* Target lesion is within a native coronary artery or major branch
* Inclusion Criteria (Additional for ISR arm):
* Reference vessel diameter is ≥ 2.0 mm and ≤ 4.0 mm
* Restenosis of stented coronary artery (Includes BMS and DES). The target lesion may have been treated with no more than 2 stents
* Target lesion is within a previously placed BMS or DES and does not extend further than 5 mm beyond either the proximal or distal edge of the stent
* Confirmed stent expansion ≥ 80% of distal reference vessel diameter by angiography and there is no malposed stent struts
* Inclusion Criteria (Additional for PK Sub-Study):
* Eligible for treatment in the ISR arm with one of the ten largest device sizes
* Inclusion Criteria (Additional for DNSV arm):
* Reference vessel diameter is ≥ 2.0 mm and ≤ 2.75 mm

Exclusion Criteria:

* Pregnant or nursing patients
* Subject presents with NSTEMI and rising biomarkers, or ongoing chest pain or is hemodynamically unstable
* Subject with history of ST-elevation myocardial infarction (STEMI) within 30 days of the index procedure
* Subject with planned major surgery within 30 days following the index procedure
* Subject with planned treatment of lesion involving aorto-ostial location
* History of previous target vessel perforation
* Cardiogenic shock
* Patients with lesions requiring interventional treatment in more than two vessels
* Extensive peripheral vascular disease that precludes safe sheath insertion
* Ostial lesion or planned future treatments
* Diffuse disease distal to target lesion with impaired runoff
* Subject is considered not able to tolerate at least 30 seconds of coronary occlusion for the target lesion treated
* Previous PCI of target vessel within 6 months prior to the procedure
* Planned PCI of any vessel within 30 days post index procedure and/or planned PCI of the target vessel within 12 months post procedure
* Currently participating or planning to participate, within 24 months of the index procedure, in an investigational drug or device trial
* Patient is a recipient of a heart transplant
* Known hypersensitivity or contraindication to aspirin, heparin, bivalirudin, or contrast agent
* History of allergic reaction or sensitivity to sirolimus or other analogue or derivative
* Known hypersensitivity to excipients with phospholipid or related origins and Poly(lactic-co-glycolic acid) (PLGA)
* Platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3 or a white blood cell count of \<3,000 cells/mm3
* Known renal insufficiency (e.g. serum creatinine \>2.5mg/dL, or creatinine clearance ≤30 mL/min), or subject on dialysis, or acute kidney failure confirmed by 50% increase of serum creatinine within 48 hours before procedure and/or decrease in urine output
* Subject with history of New York Heart Association (NYHA) class III or IV heart failure
* History of bleeding diathesis, active peptic ulcer or GI bleeding within prior 6 months or coagulopathy or will refuse blood transfusions
* Planned surgery that would cause interruption in recommended DAPT duration per current guidelines
* History of a stroke within 6 months prior to the index procedure
* Concurrent life conditions with a life expectancy of less than 24 months
* In Investigator's opinion, the patient is not a good candidate for the study
* Left ventricular ejection fraction \< 30%
* Unprotected left main coronary artery disease with ≥ 50% stenosis
* Target lesion at a bifurcation Note: A target lesion near a bifurcation is allowed if only a single vessel (either main vessel or side branch) is to be treated
* Evidence of extensive thrombus or dissection in target lesion
* Chronic total occlusion (CTO) in target lesion
* \>30% residual stenosis after pre-treatment of target lesion
* Target lesion is located in the left main or within any arterial or venous graft
* Target lesion is in a side branch that is "jailed" by a main vessel stent
* \> 50% stenosis of an additional proximal lesion or clinically significant distal lesion (in a vessel \>2.0mm RVD) to the target or non-target lesion
* Target vessel is excessively tortuous, defined as more than one bend \> 90° to reach target lesion
* Exclusion Criteria (Additional for ISR arm):
* Target lesion is the 3rd or greater stent failure (i.e., more than two \[2\] layers of stent are present at any segment of the target lesion)
* Target vessel had any previous vascular brachytherapy treatment or is planned to undergo brachytherapy at index procedure
* If single-layer ISR, any previous treatment (other than balloon angioplasty alone) of the target vessel for restenosis If double-layer ISR, any treatment (other than balloon angioplasty alone) of the double-layer ISR restenosis
* Exclusion Criteria (Additional for PK Sub-Study):
* Any limus family (Zotarolimus, Everolimus, Sirolimus etc.) eluting device has been placed/used in any part of the body within 3 months prior to the index procedure including any non-target lesion treated during the index procedure
* The subject is taking or has taken within the last 3 months any limus family medication(s) for any reason
* Subject is taking strong CYP3A4 Inhibitors within 14 days before the index procedure or plans to take the strong inhibitors during the study period (Strong inhibitors include: cobicistat; ritonavir; indinavir and ritonavir; itraconazole; ketoconazole; lopinavir and ritonavir; paritaprevir and ritonavir and ombitasvir (and/or dasabuvir); posaconazole; saquinavir and ritonavir; tipranavir and ritonavir; elvitegravir and ritonavir; telithromycin; voriconazole; ceritinib; clarithromycin; idealalisib; nefazodone; nelfinavir)
* Subject is taking strong CYP3A4 Inducers within 14 days before the index procedure or plans to take the strong inducers during the study period (Strong inducers include apalutamide; carbamazepine; enzalutamide; ivosidenib; lumacaftor and ivacaftor; mitotane; phenytoin; rifampin; St. John's wort)
* Exclusion Criteria (Additional for DNSV arm):
* Type C lesion
* Calcified or angular target lesion which cannot be pre-dilated with high pressure balloons, scoring balloon or IVL
* In-stent restenosis