Treatment of Drug-eluting Stent (DES) In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting Percutaneous Transluminal Coronary Angioplasty (PTCA) Catheter

In-Stent Restenosis Clinical Trial

Official title:

PEPCAD DES - Treatment of DES-In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting PTCA Catheter

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00998439
• Other study ID #: PEPCAD DES
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 10, 2009
• Last updated: May 19, 2011
• Start date: October 2009
• Est. completion date: December 2011

Study information

• Verified date: May 2011
• Source: Klinikum Coburg
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to assess the efficacy of the Paclitaxel-eluting PTCA - balloon catheter SeQuent® Please to treat in-stent restenoses (ISR) of various drug eluting stents in native coronary arteries with reference diameters between 2.5 mm and ≤ 3.5 mm and lesion lengths ≤ 22 mm. The vessel patency following treatment with SeQuent® Please will be documented in ISR patients that have been treated with the Cypher® or Taxus® drug eluting stent.

Description:

Background information

Current treatments for In Stent Restenosis (ISR) are 'uncoated balloon only' angioplasty with conventional balloons (POBA), Bare Metal Stent (BMS) implantations, cutting balloons, rotablation and atherectomy. Their respective results to lower target vessel revascularizations were in part unsatisfactory and often conflicting. Also the temporary use of brachytherapy lead to late lumen loss (LLL) findings in the range from 0.22 ± 0.84 mm. Therefore, brachytherapy to treat ISR has also been abandoned because of the associated delayed endothelialization leading to late thrombosis.

The use of drug eluting stents (DES) to treat ISR lowered restenosis rates in the single digit range. Recently, the use of matrix coated paclitaxel-eluting PTCA balloon catheters (SeQuent® Please, Paccocath Technology®, Bayer/Schering & B.Braun Melsungen AG) was compared to PES in the PEPCAD II trial which showed significantly lower 6-month LLL, 6-month MACE and TVR rates for SeQuent® Please (7.25%) as compared to PES for which the 12-month TVR rate was 19.0% and therefore in agreement with prior studies (ISAR DESIRE). Since these assessments were done in patients with BMS in-stent restenosis, it is of paramount interest to study in-stent restenosis of failed DES implantations since they may cause continued chronic inflammatory responses caused by the non-bioabsorbable polymer in particular once the drug release has ceased.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: December 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: Patient Related

• Patients with stable angina pectoris (CCS class 1-3) or with unstable angina pectoris (Braunwald class 1-2, A-C) or documented ischemia or with documented silent ischemia

• Patients eligible for coronary revascularization by means of PCI

• Patients suitable for coronary revascularization of any sort (balloon angioplasty, device-assisted balloon-angioplasty, or coronary artery bypass grafting)

• Patients must be = 18 years of age

• Women of childbearing potential may not be pregnant nor have the desire to becoming pregnant during the first year following the study procedure. Hence, patients will be advised to use an adequate birth control method up to and including 6 months follow-up

• Patients who are mentally and linguistically able to understand the aim of the study and to show sufficient compliance in following the study protocol

• Patients must agree to undergo the 6 months angiographic follow-up

• Patients must agree to undergo the 1 and 3 year clinical follow-up

• Patient is able to verbally acknowledge an understanding of the associated risks, benefits, and treatment alternatives to therapeutic options of this trial, e.g., balloon angioplasty by means of the paclitaxel-eluting PTCA-balloon catheter or other suitable devices. The patients, by providing their informed consent, agree to these risks and benefits as stated in the patient informed consent document.

Inclusion Criteria: Lesion Related

• In-stent restenosis or Mehran type III stenoses reaching = 2 mm into the adjacent native vessel of a drug eluting stent (DES), in a native coronary artery (reference vessel between = 2.5 and = 3.5 mm, lesion length = 22 mm as angiographically documented)

• Diameter stenosis pre procedure must be either = 70 % or = 50 % if ischemia corresponding to the target lesion is documented either by exercise stress ECG, stress echocardiography, scintigraphy, MRT, or suspected based on angina pectoris.

• DES in-stent restenosis independent of the the number of metal layers (e.g. restenosed DES following BMS and/or DES implantation(s))

Exclusion Criteria: Patient Related

• Patients with acute (< 24 h) or recent (48 hours) myocardial infarction

• Patients with unstable angina pectoris (Braunwald class 3)

• Patients with severe congestive heart failure

• Patients with severe heart failure NYHA IV

• Patients demonstrating clinical signs of cardiogenic shock at the time of the procedure (systolic blood pressure of less than 80 mmHg requiring inotropic support, IABP and/or fluid challenge)

• Patients with severe valvular heart disease

• Women who are pregnant or lactating patients with life expectancy of less than five years or factors making clinical follow-up difficult

• Patients with another coronary stent previously implanted into the target vessel

• Patients with bleeding diathesis in whom anticoagulation or anti-platelet medication is contraindicated

• Patients who had a cerebral stroke < 6 months prior to the procedure

• Patient participates in other clinical trials involving any investigational device or drug

• Untreated hyperthyroidism

• Patient has presence or history of severe renal failure (GFR < 30ml/min) and is therefore not eligible for angiography. Patient's serum creatinine levels must be documented.

• Post transplantation of any organ or immune suppressive medication

• Other disease to jeopardize follow-up (e.g. malignoma)

• Addiction to any drug or to alcohol

• Patients with any type of surgery during the week preceding the interventional procedure

• Conditions which prevent the intake of the double anti-platelet therapy for three months

Exclusion Criteria: Lesion Related

• Evidence of extensive thrombosis within target vessel before the intervention

• Side branch > 2 mm in diameter originating from the stent

• Bifurcate lesion

• Left main coronary artery stenosis

• Multilesion percutaneous coronary intervention within the same artery (a main artery e.g., LCX and its side branch e.g. OMS are considered as different arteries)

• Percutaneous coronary intervention of venous graft

• Coronary artery occlusions of any type (e.g. acute or chronic)

• In-segment stenosis of the native vessel within the 5 mm adjacent to the stent

• Lesion within 1 mm of vessel origin

Exclusion Criteria: Related to Concomitant Medication

• Patient is intolerant to aspirin and/or the ADP-antagonists clopidogrel or has a history of neutropenia, thrombocytopenia induced by ADP-antagonists, or severe hepatic dysfunction prohibiting the use of clopidogrel

• Patient has leucopoenia (leukocyte count < 109/liter for more than 3 days)

• Patient has neutropenia (ANC < 1000 neutrophils/mm3 for more than 3 days)

• Patient has a history of peptic ulcer or gastric/intestinal bleeding during the past 6 months

• Patient has a history of thrombocytopenia (< 100,000 platelets/mm3)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• In-Stent Restenosis

Intervention

Device:
• SeQuent® Please
6 F, 7 F, or 8 F guiding catheters have to be used after insertion of arterial sheath, apply heparin (7,500-10,000 Units i.a. or i.c. (or 50-100 U/kg body weight)) additional dose of 5,000 Units (75 U/kg body weight) if procedure lasts for more than one hour Nitroglycerin (0.2 mg i.c.) prior to first contrast injection ISR must be predilated with uncoated balloon balloon diameter shall be 0.5 mm smaller than the Paclitaxel-eluting balloon intended for use inflation time has to be = 30 sec select balloon with correct stent diameter to achieve a remaining stenosis of = 10 % each Paclitaxel-eluting balloon catheter is allowed for single use only additional inflations and/or aggressive anti-platelet agents for intraluminal defects or haziness if additional balloon is necessary, only uncoated balloon is permitted to avoid overdosing of drug
• SeQuent® II
6 F, 7 F, or 8 F guiding catheters have to be used after insertion of arterial sheath, apply heparin (7,500-10,000 Units i.a. or i.c. (or 50-100 U/kg body weight)) additional dose of 5,000 Units (75 U/kg body weight) if procedure lasts for more than one hour Nitroglycerin (0.2 mg i.c.) prior to first contrast injection ISR must be predilated with uncoated balloon balloon diameter shall be 0.5 mm smaller than the Paclitaxel-eluting balloon intended for use inflation time has to be = 30 sec select balloon with correct stent diameter to achieve a remaining stenosis of = 10 % each Paclitaxel-eluting balloon catheter is allowed for single use only additional inflations and/or aggressive anti-platelet agents for intraluminal defects or haziness if additional balloon is necessary, only uncoated balloon is permitted to avoid overdosing of drug

Locations

Country	Name	City	State
Germany	Zentralklinik Bad Berka GmbH	Bad Berka
Germany	Klinikum Bayreuth	Bayreuth
Germany	Klinikum Coburg	Coburg
Germany	Klinikum Kulmbach	Kulmbach
Germany	Herzzentrum Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck
Germany	LMU - Klinikum der Universität München	Munich
Germany	Klinikum Weiden	Weiden

Sponsors (1)

Lead Sponsor	Collaborator
Klinikum Coburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Late lumen loss		6 months	No
Secondary	Occurrence of acute (up to 48 hours), subacute (up to 30 days), and late thrombosis		3 years	Yes
Secondary	Major adverse cardiac event (MACE) rate		30 days	Yes
Secondary	Percent in-stent stenosis		6 months	No
Secondary	Percent in-segment stenosis		6 months	No
Secondary	In-stent late loss index		6 months	No
Secondary	Angiographic binary in-stent stenosis rate		6 months	No
Secondary	In-segment late loss index		6 months	No
Secondary	Angiographic binary in-segment stenosis rate		6 months	No
Secondary	Indication for premature follow-up		6 months	No
Secondary	Type of recurrence (Mehran-Classification)		6 months	No
Secondary	Target vessel failure		6 months	No
Secondary	MACE Rate		6 months	Yes
Secondary	MACE Rate		1 year	Yes
Secondary	MACE Rate		3 years	Yes