Comparison of Agent™ and SeQuent® Please Paclitaxel Coated Balloon Catheters in Coronary In-stent Restenosis (AGENT-ISR)

Study Overview
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Brief Summary
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The primary objective of this study is determine the safety and performance of the Agent™ Paclitaxel-Coated PTCA Balloon Catheter compared to the SeQuent® Please Paclitaxel-Releasing Coronary Balloon Catheter for the treatment of patients with narrowed previously-stented coronary arteries (in-stent restenosis). The performance will be determined at six months post-procedure by quantitative coronary angiography (QCA) to measure Late Lumen Loss (LLL) in the re-opened stented segment. QCA results will be assessed by an independent, blinded angiographic core lab. Study statistical hypothesis: The loss of in-stent luminal diameter at six months after treatment of the restenosed stent with the Agent™ study device is not larger than the respective LLL after treatment with the SeQuent® Please control devices, i.e. study device is non-inferior to the control device with respect to LLL.

Official Title
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A Prospective Randomized Multicenter Non-inferiority Clinical Study to Determine the Safety and Performance of the Agent™ Paclitaxel-Coated PTCA Balloon Catheter (Hemoteq) Compared to the SeQuent® Please Paclitaxel-Releasing Coronary Balloon Catheter (B.Braun) for the Treatment of Coronary In-Stent Restenosis (AGENT-ISR)

Conditions
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Coronary Artery Disease, Coronary Restenosis, Coronary Atherosclerosis, Coronary Arteriosclerosis

Intervention / Treatment
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* Device: Agent Paclitaxel-coated balloon
* Device: SeQuent® Please Paclitaxel-coated Balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be at least 18 years of age Subject is willing and able to provide informed consent Subject is eligible for percutaneous coronary intervention Subject is willing to comply with all protocol-required follow-up evaluations Women of child-bearing potential must agree to use a reliable method of contraception In-stent restenosis in a lesion previously treated with either a drug-eluting or bare metal stent, located in a native coronary artery with a reference vessel diameter ≥ 2.0 mm and ≤ 3.5 mm Target lesion length must be ≤ 28 mm (by visual estimate) and must be covered by only one balloon Target lesion must have visually estimated stenosis ≥ 70% and < 100% in asymptomatic patients Target lesion must have visually estimated stenosis ≥ 50% and < 100% in symptomatic patients Thrombolysis in Myocardial Infarction (TIMI) grade flow in the target lesion must be ≥ 1 Target lesion must be successfully pre-dilated. Exclusion Criteria: Patient has life expectancy of less than 24 months Patient with known coronary artery spasm Patient with unprotected left main coronary artery disease Patient has current problems with substance abuse Patient has planned procedure that may cause non-compliance with the protocol or confound data interpretation Patient is participating in another investigational drug or device clinical study that has not reached its primary endpoint Patient intends to participate in another investigational drug or device clinical study within 12 months after the index procedure Woman who is pregnant or nursing Left ventricular ejection fraction < 25% Patient had PCI or other coronary interventions within the last 30 days Planned PCI or CABG after the index procedure Patient to receive other PCI interventions in the target vessel, such as rotablation, laser atherectomy, cutting balloon, DCB, DES, BMS, bioabsorbable scaffold etc. Patient to receive DCB in non-target coronary vessels Acute MI < 72h Cardiogenic shock Known allergies against Paclitaxel or other components of the used medical devices Known hypersensitivity or contraindication for contrast dye that cannot be adequately pre-medicated Intolerance to antiplatelet drugs, anticoagulants required for the procedure Platelet count < 100k/mm3 or > 500k/mm3 Patient with renal failure with a serum creatinine of > 2.5mg/dL who is receiving dialysis or chronic immunosuppressant therapy Target lesion is located within a bifurcation involving a major side branch > 2 mm in diameter Target lesion is located within a saphenous vein graft or an arterial graft Target lesion with TIMI grade flow = 0 (total occlusion) Thrombus present in the target vessel > 50% stenosis of an additional lesion proximal or distal to the target lesion

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Agent Paclitaxel-coated balloon<br>drug-coated balloon dilatation of the index lesion using a single Agent(TM) balloon that completely covers the restenotic lesion | Device: Agent Paclitaxel-coated balloon<br>* After successful pre-dilatation, the index lesion is dilated with a single drug-coated balloon that completely covers the restenotic lesion.<br>|
| Active Comparator: SeQuent Please Paclitaxel-coated balloon<br>drug-coated balloon dilatation of the index lesion using a single SeQuent(R) Please balloon that completely covers the restenotic lesion | Device: SeQuent® Please Paclitaxel-coated Balloon<br>* After successful pre-dilatation, the index lesion is dilated with a single drug-coated balloon that completely covers the restenotic lesion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| in-stent late lumen loss | In-stent late lumen loss (LLL) of the treated stented segment after PTCA using the Agent(TM) study device in comparison to the LLL after PTCA using the SeQuent(R) Please control device as measured by QCA at six months post-index procedure. | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| technical success rate | The ability to cross and dilate the lesion to achieve residual angiographic stenosis no greater than 30 percent | during index procedure, less 1 hour | 
| clinical procedural success rate | Technical success with no composite of all death and MI noted within 24 hours of the index procedure. | within 24 hours of index procedure | 
| In-stent percent diameter stenosis | In-stent percent diameter reduction measured within the borders of the stent | 6 months post-index procedure | 
| In-segment percent diameter stenosis | In-segment percent diameter reduction measured in the stented segment plus 5mm on either side. | 6 months post-index procedure | 
| In-stent binary restenosis rate | In-stent binary restenosis is defined as ≥50% luminal narrowing within the borders of the stent observed at follow-up QCA. | 6 months post-index procedure | 
| In-segment binary restenosis rate | In-segment binary restenosis is defined as ≥50% luminal narrowing in the stented segment plus 5mm on either side observed at follow-up QCA. | 6 months post-index procedure | 
| In-segment late lumen loss | In-segment late lumen loss is the in-segment minimal lumen diameter (MLD) post index procedure minus the in-segment MLD at 6 months follow-up as determined by QCA. | 6 months post-index procedure | 
| In-stent minimal lumen diameter (MLD) | In-stent MLD is measured within the borders of the stent. | 6 months post-index procedure | 
| In-segment minimal lumen diameter (MLD) | In-segment MLD is measured in the stented segment plus 5mm on either side. | 6 months post-index procedure | 
| Target lesion revascularization (TLR) rate | TLR rate during index in-hospital stay | pre-discharge, estim. <10 days | 
| Target lesion revascularization (TLR) rate |  | 30 days | 
| Target lesion revascularization (TLR) rate |  | six months | 
| Target lesion revascularization (TLR) rate |  | 12 months | 
| Target lesion revascularization (TLR) rate |  | 24 months | 
| Target lesion revascularization (TLR) rate |  | 36 months | 
| Target vessel revascularization (TVR) rate | TVR rate during index in-hospital stay | pre-discharge, estim. <10 days | 
| Target vessel revascularization (TVR) rate |  | 30 days | 
| Target vessel revascularization (TVR) rate |  | six months | 
| Target vessel revascularization (TVR) rate |  | 12 months | 
| Target vessel revascularization (TVR) rate |  | 24 months | 
| Target vessel revascularization (TVR) rate |  | 36 months | 
| Cardiac, non-cardiac and all death rates | rates during index in-hospital stay | pre-discharge, estim. <10 days | 
| Cardiac, non-cardiac and all death rates |  | 30 days | 
| Cardiac, non-cardiac and all death rates |  | six months | 
| Cardiac, non-cardiac and all death rates |  | 12 months | 
| Cardiac, non-cardiac and all death rates |  | 24 months | 
| Cardiac, non-cardiac and all death rates |  | 36 months | 
| Myocardial infarction rates (by 3rd Universal Definition: all MI, QWMI, NQWMI) | rates during index in-hospital stay | pre-discharge, estim. <10 days | 
| Myocardial infarction rates (by 3rd Universal Definition: all MI, QWMI, NQWMI) |  | 30 days | 
| Myocardial infarction rates (by 3rd Universal Definition: all MI, QWMI, NQWMI) |  | six months | 
| Myocardial infarction rates (by 3rd Universal Definition: all MI, QWMI, NQWMI) |  | 12 months | 
| Myocardial infarction rates (by 3rd Universal Definition: all MI, QWMI, NQWMI) |  | 24 months | 
| Myocardial infarction rates (by 3rd Universal Definition: all MI, QWMI, NQWMI) |  | 36 months | 
| Stent thrombosis rate (by ARC definition) | rates during index in-hospital stay | pre-discharge, estim. <10 days | 
| Stent thrombosis rate (by ARC definition) |  | 30 days | 
| Stent thrombosis rate (by ARC definition) |  | six months | 
| Stent thrombosis rate (by ARC definition) |  | 12 months | 
| Stent thrombosis rate (by ARC definition) |  | 24 months | 
| Stent thrombosis rate (by ARC definition) |  | 36 months | 
| Target lesion failure (TLF) rate (composite of cardiac death, MI and TLR) | rates during index in-hospital stay | pre-discharge, estim. <10 days | 
| Target lesion failure (TLF) rate (composite of cardiac death, MI and TLR) |  | 30 days | 
| Target lesion failure (TLF) rate (composite of cardiac death, MI and TLR) |  | six months | 
| Target lesion failure (TLF) rate (composite of cardiac death, MI and TLR) |  | 12 months | 
| Target lesion failure (TLF) rate (composite of cardiac death, MI and TLR) |  | 24 months | 
| Target lesion failure (TLF) rate (composite of cardiac death, MI and TLR) |  | 36 months | 
| Target vessel failure (TVF) rate (composite of cardiac death, MI and TVR) | rates during index in-hospital stay | pre-discharge, estim. <10 days | 
| Target vessel failure (TVF) rate (composite of cardiac death, MI and TVR) |  | 30 days | 
| Target vessel failure (TVF) rate (composite of cardiac death, MI and TVR) |  | six months | 
| Target vessel failure (TVF) rate (composite of cardiac death, MI and TVR) |  | 12 months | 
| Target vessel failure (TVF) rate (composite of cardiac death, MI and TVR) |  | 24 months | 
| Target vessel failure (TVF) rate (composite of cardiac death, MI and TVR) |  | 36 months | 
| Change in Quality of Life | Functional status of general health-related quality of life (QoL) measured by changes in SF-12 scores and EQ5D scores as compared to baseline | six months | 
| Change in Quality of Life | Functional status of general health-related quality of life (QoL) measured by changes in SF-12 scores and EQ5D scores as compared to baseline | 12 months | 
| Change in Quality of Life | Functional status of general health-related quality of life (QoL) measured by changes in SF-12 scores and EQ5D scores as compared to baseline | 24 months | 
| Change in Quality of Life | Functional status of general health-related quality of life (QoL) measured by changes in SF-12 scores and EQ5D scores as compared to baseline | 36 months |