Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-Stent Restenosis 4 (ISAR-DESIRE 4)

ISAR-DESIRE 4: Randomized Trial Of Scoring Balloon in Patients With Restenosis in "Limus"-Eluting Coronary Stents Undergoing Angioplasty With Paclitaxel-Coated Balloon

The purpose of the study is to determine whether scoring balloon (SCB) plus paclitaxel-coated balloon (PCB) is superior to PCB alone for the treatment of restenosis within "limus"-eluting stents (LES)

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome; Stable Angina Pectoris; Restenosis
• Intervention / Treatment: Device: Paclitaxel Eluting Balloon + Scoring Balloon; Device: Paclitaxel Eluting Balloon

Detailed Description

The optimal treatment of in-BMS-restenosis seems to be implantation of a DES which is supported by a large body of evidence. Nevertheless, several recent published studies have shown a substantial reduction in late lumen loss and angiographic restenosis using paclitaxel-coated balloons (PCB) for restenotic lesions. Given the increased world-wide use of DES and the use of DES in increasingly complex coronary disease patterns, the number of patients presenting with restenosis after DES implantation will further increase in the coming decade.

Data regarding the optimal treatment of in-DES-restenosis are very limited: Implanting a new DES for in-DES-restenosis has been reported to associate with repeat restenosis rates as high as 20%. In addition, an increased risk of stent thrombosis has been associated with complex stenting and with additional DES implantation. Thus, for lesions which develop restenosis after LES implantation, the optimal treatment strategy remains unknown.

Few results on small sample-size populations have been reported in patients treated with scoring or cutting balloon (SCB) technology for treatment of BMS restenosis as compared to plain balloon angioplasty. Moreover, the efficacy of SCB angioplasty in DES restenosis has not been adequately addressed. Furthermore, the potential additive benefit of SCB angioplasty in patients undergoing PCB therapy remains to be elucidated. The hypothesis behind this concept is that the application of SCB prior to deployment of PCB may increase the bioavailability of paclitaxel within the restenotic tissue, and therefore may increase the efficacy of PCB. There are numerous preclinical studies to support this hypothesis, which show that lesion preparation is an important pre-requisite for the effectiveness of PCB.

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80636
      • Deutsches Herzzentrum Muenchen
    • Munich, Bavaria, Germany, 81675
      • 1. Med. Klinik am Klinikum rechts der Isar der TU Muenchen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥ 50% restenosis after prior implantation of LES in native coronary vessels.
• Written, informed consent by the patient or her/his legally-authorized representative for participation in the study.
• In women with childbearing potential a negative pregnancy test is mandatory.

Exclusion Criteria:

• Age < 18 years
• Cardiogenic shock
• Acute ST-elevation myocardial infarction within 48 hours from symptom onset.
• Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) with life expectancy less than 12 months or that may result in protocol non-compliance.
• Severe renal insufficiency (glomerular filtration rate ≤ 30 ml/min)
• Contraindications to antiplatelet therapy, paclitaxel, stainless steel, cobalt, chrome
• Therapy including Lovastatin, Ciclosporin, Terfenadine, Midazolam, or Ondansetron
• Pregnancy (present, suspected or planned) or positive pregnancy test.
• Previous enrollment in this trial.
• Patient's inability to fully comply with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paclitaxel Eluting Balloon + Scoring Balloon; Dilatation of the lesion with an Paclitaxel Eluting Balloon before the utilization of a Scoring Balloon	Device: Paclitaxel Eluting Balloon + Scoring Balloon; Scoring/cutting balloon lesion predilation; paclitaxel eluting balloon therapy
Active Comparator: Paclitaxel Eluting Balloon	Device: Paclitaxel Eluting Balloon; Standard balloon lesion predilation; paclitaxel-eluting balloon therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-segment percent diameter stenosis	In-segment percent diameter stenosis (%DS) at 6-8 month follow-up angiography	6-8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-stent late lumen loss	The difference between minimal lumen diameter post-procedure and minimal lumen diameter at follow-up angiography	6-8 months
In-segment binary angiographic restenosis	diameter stenosis ≥50% in the in-segment area (including the interventional area as well as 5 mm margins proximal and distal) at follow-up angiography	6-8 month
Death or myocardial infarction	Combined incidence of death or myocardial infarction at one and two year	1 and 2 years
Target lesion revascularization	Need for target lesion revascularization (TLR), defined as any revascularization procedure involving the target lesion due to luminal re-narrowing in the presence of symptoms or objective signs of ischemia at one and two year follow-up	1 and 2 years
Target lesion thrombosis	Incidence of target lesion thrombosis at one and two years	1 and 2 years
OCT tissue characterization	Tissue characterization following application of SCB and PCB using OCT at 6 -8 months follow up	6-8 months

Collaborators and Investigators

• Sponsor: Deutsches Herzzentrum Muenchen
• Collaborators: Biotronik AG
• Investigators: Study Chair: Adnan Kastrati, MD, Deutsches Herzzentrum Munich; Principal Investigator: Robert Byrne, MB PhD, Deutsches Herzzentrum Munich

Publications and helpful links

General Publications

• Kufner S, Joner M, Schneider S, Tolg R, Zrenner B, Repp J, Starkmann A, Xhepa E, Ibrahim T, Cassese S, Fusaro M, Ott I, Hengstenberg C, Schunkert H, Abdel-Wahab M, Laugwitz KL, Kastrati A, Byrne RA; ISAR-DESIRE 4 Investigators. Neointimal Modification With Scoring Balloon and Efficacy of Drug-Coated Balloon Therapy in Patients With Restenosis in Drug-Eluting Coronary Stents: A Randomized Controlled Trial. JACC Cardiovasc Interv. 2017 Jul 10;10(13):1332-1340. doi: 10.1016/j.jcin.2017.04.024.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: June 26, 2012
• First Submitted That Met QC Criteria: June 28, 2012
• First Posted (Estimate): July 2, 2012

Study Record Updates

• Last Update Posted (Estimate): November 21, 2016
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: In-stent Restenosis; Drug Eluting Stent; Paclitaxel Coated Balloon; Scoring Balloon; Cutting Balloon; Angiographic follow-up; Optical coherence tomography (OCT)
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Acute Coronary Syndrome; Angina Pectoris; Angina, Stable; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: GE IDE NO. S00112; CIV-12-05-006401 (Other Identifier: European Databank on Medical Devices (EUDAMED))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No