Resveratrol Excipient Paclitaxel Coated Balloon for Coronary Treatment

A Prospective, Randomized, Multi-center IDE Study to Assess the SeQuent Please ReX Drug Coated PTCA Balloon Catheter for the Treatment of In-stent Restenosis (RESPECT-ISR)

The objective of this study is to establish reasonable assurance of safety and effectiveness to support an FDA premarket approval (PMA) application for the SeQuent® Please ReX™ Drug Coated PTCA Balloon Catheter as indicated.

The investigation is a prospective, randomized, multi-center IDE study comparing the SeQuent Please ReX to plain old balloon angioplasty (POBA). The study will be conducted at up to 30 investigational sites and enroll up to 296 patients with in-stent restenosis of a metallic coronary stent who are suitable candidates for PTCA procedures. After consent and assessment of inclusion and exclusion criteria, eligible patients will be randomized to either the SeQuent Please ReX or POBA arm based on a 2:1 randomization ratio. Subjects will return for follow-up through 5 years.

INCLUSION CRITERIA:

1. ISR (>50%) of a metallic coronary stent of any type (BMS or DES)

2. Symptomatic ischemic heart disease, including:

   • Chronic stable angina (and/or objective evidence of myocardial ischemia on functional study or fractional flow reserve [FFR] measurement) or
   • Acute coronary syndrome (unstable angina or non-ST-elevation myocardial infarction (NSTEMI)), who require elective or urgent percutaneous coronary intervention (PCI)

3. One or two ISR lesions requiring treatment

   • ISR lesions may be located in two different vessels
   • Additional non-ISR (de novo) lesions are permitted and may be located in the target or other vessels

4. Target lesion reference vessel diameter is ≥2.0 or ≤4.0 mm by visual estimation

5. Total lesion length less than or equal to 34 mm by visual estimation (to permit treatment with balloon up to 40 mm)

6. Male or female, age 18 years or older

7. Willing to provide written informed consent and written HIPAA authorization prior to initiation of study procedures

8. Willing to comply with the specified follow-up visits

9. Willing and able to comply with post-treatment medications (dual antiplatelet therapy (DAPT) followed by life-long aspirin)

10. Non-target lesions must be treated successfully (i.e., residual diameter stenosis <30% without complications) before proceeding to treatment of ISR lesion(s)

EXCLUSION CRITERIA:

1. Target lesion has undergone more than two prior stent implant procedures, i.e., more than two layers of stent are present at any segment of target lesion
2. Presents with ST-elevation myocardial infarction (STEMI)
3. STEMI within the past 72 hours
4. Chronic kidney disease, defined as glomerular filtration rate (GFR) <15 ml/min/1.73m^2 on baseline labs
5. Thrombocytopenia, defined as a platelet count of <50,000 microL on baseline labs
6. Target lesion is a chronic total occlusion
7. Bleeding diathesis, coagulopathy, or contraindication to antiplatelet therapy
8. Target lesion restenosis is within a bio-resorbable scaffold
9. Target lesion is located within the left main
10. Pregnant (verified with a urine or blood pregnancy test), breast-feeding, or planning to become pregnant
11. Severely disabled and/or life expectancy appears limited (≤12 months) according to the investigator's opinion
12. Known hypersensitivity to paclitaxel and/or resveratrol or any of the product ingredients
13. Currently participating in an investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints

Note: Bifurcation lesions are not excluded; however, the main branch should be treated per randomization, and the side branch should be treated provisionally per current standard of care.

Angiographic Exclusion Criteria:

Subjects must not meet any of the following angiographic exclusion criteria after lesion preparation:

1. Dissection type C - F
2. TIMI < III
3. Residual stenosis >30%