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

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)

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Coronary Arteriosclerosis; Coronary Atherosclerosis; Coronary Restenosis
• Intervention / Treatment: Device: Agent Paclitaxel-coated balloon; Device: SeQuent® Please Paclitaxel-coated Balloon

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69007
    • Centre Hospitalier Saint Joseph Saint Luc de Lyon
  • Montpellier, France, 34000
    • Clinique du Millénaire, Montpellier
  • Montpellier, France, 34090
    • CHU Montpellier, Hôpital Arnaud de Villeneuve
  • Nantes, France, 44093
    • CHU de Nantes, Hôpital Laennec
  • Rouen, France, 76000
    • Clinique Saint Hilaire, Rouen
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
  • Giessen, Germany, 35392
    • University Giessen
  • Reutlingen, Germany, 72764
    • Klinikum am Steinenberg
  • Rostock, Germany, 18057
    • Universitaetsklinikum Rostock
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Agent Paclitaxel-coated balloon; 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; After successful pre-dilatation, the index lesion is dilated with a single drug-coated balloon that completely covers the restenotic lesion.
Active Comparator: SeQuent Please Paclitaxel-coated balloon; 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; After successful pre-dilatation, the index lesion is dilated with a single drug-coated balloon that completely covers the restenotic lesion.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hemoteq AG
• Investigators: Principal Investigator: Christian W. Hamm, MD, University Giessen, Germany

Publications and helpful links

General Publications

• Hamm CW, Dorr O, Woehrle J, Krackhardt F, Ince H, Zeus T, Berland J, Piot C, Roubille F, Schult I, Allocco DJ, Nef H. A multicentre, randomised controlled clinical study of drug-coated balloons for the treatment of coronary in-stent restenosis. EuroIntervention. 2020 Jul 17;16(4):e328-e334. doi: 10.4244/EIJ-D-19-00051.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2014
• Primary Completion (Actual): April 27, 2017
• Study Completion (Actual): October 28, 2019

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Coronary Disease; Coronary Stenosis; Coronary Artery Disease; Myocardial Ischemia; Arteriosclerosis; Atherosclerosis; Coronary Restenosis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: HTQ002-Agent-ISR; CIV-13-11-011728 (Other Identifier: EUDAMED)