Intimal Hyperplasia Evaluated by Optical Coherence Tomography (OCT) in de Novo Coronary Lesions Treated by Drug-eluting Balloon and Bare-metal Stent (IN-PACT CORO)
Recruitment status was Recruiting
|First Received Date ICMJE||January 26, 2010|
|Last Updated Date||January 26, 2010|
|Start Date ICMJE||November 2009|
|Estimated Primary Completion Date||November 2010 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Primary Endpoint: Neo-intimal area (mm²). [ Time Frame: 6 months post procedure ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
||Secondary Endpoints: - 6m percentage of uncovered struts. - 6m percentage of struts with ISA. - 6m percentage of protruding struts. [ Time Frame: 6 months post procedure ] [ Designated as safety issue: No ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Intimal Hyperplasia Evaluated by Optical Coherence Tomography (OCT) in de Novo Coronary Lesions Treated by Drug-eluting Balloon and Bare-metal Stent|
|Official Title ICMJE||IN-PACT CORO INtimal hyPerplasia evAluated by oCT in de Novo COROnary Lesions Treated by Drug-eluting Balloon and Bare-metal Stent|
Restenosis due to neointimal hyperplasia causes repeat target vessel revascularization in a relevant number of patients undergoing percutaneous coronary interventions (PCI). Drug-eluting stents (DES) are currently adopted to reduce the rate of restenosis; however, they may increase risk of stent thrombosis.
Experimental data and first clinical experiences showed that inhibition of neointimal hyperplasia may be obtained by local administration of anti-proliferative drugs (like paclitaxel) loaded on the surface of angioplasty balloons. Data on the efficacy of novel coronary drug-eluting balloons (DEBs) are lacking.
Aims of this open label prospective, randomized trial is to evaluate neointimal hyperplasia in patients undergoing bare-metal stent (BMS) implantation alone compared to those receiving additional DEB use and to assess if the technique of DEB use may affect the degree of neointimal hyperplasia.
Neointimal hyperplasia will be assessed by Optical coherence tomography (OCT).
Background. Restenosis due to neointimal hyperplasia causes repeat target vessel revascularization in a relevant number of patients undergoing percutaneous coronary interventions (PCI). Drug-eluting stents (DES) are currently adopted to reduce the rate of restenosis and repeat revascularizations in the majority of cases. However, a known drawback that limits the clinical application of DES technology is the possible increased risk of stent thrombosis, requiring the need of a prolonged dual antiplatelet therapy. Such phenomenon is strongly related to the profound inhibition of stent strut endothelization, that leads to the presence of uncovered stent struts, and to the persistence of polymer molecules which may induce inflammatory reactions in the vessel wall.
Experimental data and first clinical experiences showed that inhibition of neointimal hyperplasia may be obtained by local administration of anti-proliferative drugs (like paclitaxel) loaded on the surface of angioplasty balloons. Accordingly, drug-eluting balloons (DEBs) are a promising tool to prevent restenosis and avoid the undesiderable persistence of polymer molecules of DES in the vessel wall, thus potentially increasing the safety of PCI Data on the efficacy of novel coronary DEBs and on the best technique to use them are lacking.
Optical coherence tomography (OCT), has a resolution of 5-10 μm, 10 times higher than intravascular ultrasound, thus allowing fine characterization of stent strut coverage and apposition and detection of minimal degree of in-stent neointima hyperplasia.
Objective of the study:
Study Design. Open label prospective randomized trial comparing the degree of neointimal hyperplasia assessed by OCT in patients treated by BMS implantation alone, BMS implantation after DEB predilation or BMS followed by DEB postdilation.
Consecutive patients undergoing BMS implantation and agreeing to enter the study will be randomized 1:1:1 to
Study population. 30 subjects.
Procedure Description. In all eligible patients, PCI with BMS implantation will be performed according to the physician standard practice. All patients will be pre-treated with dual antiplatelet therapy.
General considerations on DEB usage. DEB is mainly intended to serve as drug delivery to the vessel wall and should therefore always cover the stenotic area as well as any extended pre-treated (injured) vessel area including the target lesion and any adjacent (prox and distal) portions when these were eventually previously covered by a stent or dilated by a balloon catheter, incidentally or by intention.
DEB length and positioning within the target lesion must be therefore carefully chosen to avoid geographic miss between the DEB and such extended pre-treated vessel area.
The result of the procedure will be assessed by 3-dimensional QCA.
Post-procedural management. All patients will undergo cardiac damage markers (Creatin-kinase-MB and Troponin I) assessment before the procedure, 6 hours after PCI and 24 hours after PCI. Thereafter, further blood samples will be performed only if clinically indicated.
After PCI, patients will be given aspirin (75-100 mg/die) life-long and clopidogrel (75 mg/die) for 3 months (according to the on-label prescription for DEB-treated patients).
Follow-up. Clinical follow-up will take place at 1 month (±1 week), 6 months (±2 weeks) and 1 year (±30 days). At 6-month follow-up all patients will undergo a quantitative coronary angiography (3-dimensional QCA) and Optical Coherence Tomography (OCT) study.
OCT analysis. OCT will be performed with the Imaging system M2 (LightLab Imaging Inc., Westford, Massachusetts), capable of a pullback speed of 2 mm/sec and acquisition frame rate of 15.6/sec, using a non-occlusive technique, with continuous intracoronary iso-osmolar contrast injection.
The entire stent length will be assessed and cross sectional images will be analysed every 0.5 mm.
STRUT COVERAGE The struts will be classified as uncovered if a tissue layer on the endoluminal surface is not visible or covered in the presence of visibile tissue between the endoluminal surface and the lumen.
The tissue coverage thickness will be measured in each strut as the distance from the strut endoluminal surface to the lumen. In each cross section analysed, the following parameters will be calculated: the percentage of covered struts (the number of covered struts/ total number of struts), the percentage of uncovered struts (number of uncovered struts/ total number of struts), the tissue coverage thickness (μm), the tissue coverage area (stent area - lumen area) and its percentage (tissue coverage area/stent area X 100); the tissue volume coverage (tissue coverage area x stent length) and its percentage (tissue coverage volume/stent volume X 100). To assess the pattern of coverage, the ratio between the difference of maximum and the minimum tissue thickness/maximum tissue coverage will be calculated in each frame. A ratio close to 1 indicates an asymmetric tissue coverage, on the opposite a ratio close to 0 indicates a symmetric tissue coverage.
INCOMPLETE STENT APPOSITION A single stent strut will be defined with incomplete stent apposition (ISA) when the distance between its endoluminal surface and the vessel wall will be higher than the entire strut thickness. ISA will be considered present if at least one single strut will be incompletely apposed to the vessel wall. In each OCT frame analysed, the number of struts with ISA and the maximum distance from the endoluminal stent strut to the vessel wall will be measured. The percentage of struts with ISA (number of struts with ISA/total number of struts), according to the presence/absence of tissue coverage, will also be reported. A strut will be defined as protruding when the strut will protrude into the lumen relative to the intima between the adjacent strut sections and the distance between its endoluminal surface and the vessel wall will be less than the entire strut thickness and higher than half of strut thickness. The percentage of protruding struts (number of protruding struts/total number of strut X 100) will be reported, according to the presence/absence of tissue coverage.
Sample size calculation and statistical analysis. The primary endpoint is the neointimal area. Secondary endpoints will be the percentage of uncovered struts, the percentage of struts with ISA and the percentage of protruding struts.
This OCT study is a superiority study and it is expected that additional DEB use to BMS implantation will lead to a reduction of the primary endpoint compared to BMS implantation alone.
Few information is available on neointimal proliferation after BMS implantation: two small non randomized studies reported maximal and minimal neointimal thickness (mm) at 7.3 month follow up (first study) and mean neointimal thickness at 8 month follow up (latter study) being > 4 folds higher in the BMS group compared to the rapamycin eluting stent group, although data on neointimal area are not available. A recent randomized study comparing 12 polymer coated rapamycin-eluting stents to 12 non polymer rapamycin eluting stents reported a neointimal area of 0.3 ± 0.2 mm2 in the polymer stent vs 1.2 ± 0.8 mm2in the non polymer stent, thus with a difference of 0.9 (95% CI 0.3-1.4). Based on these findings, we may hypothesize that additional DEB use will yield to a value of neointimal area close to that reported in the non polymer rapamycin eluting stent and that this would correspond to approximately 50% reduction of neointimal area in the BMS group. To detect such difference, 10 patients will be required in each group with a power of 0.9 at a two- sided type I error of 0.05. As we cannot anticipate whether the timing of additional DEB use: pre or post stenting, might have a different effect on the reduction of neointimal hyperplasia, 10 patients will be allocated in a randomized fashion to the predilatation DEB use group, 10 patients to the postdilatation DEB use group and 10 to the BMS group.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Coronary Artery Disease|
|Study Arm (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||30|
|Completion Date||Not Provided|
|Estimated Primary Completion Date||November 2010 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both (female sex with child-bearing potential excluded) Accepts Healthy Volunteers: No
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||Italy|
|NCT Number ICMJE||NCT01057563|
|Other Study ID Numbers ICMJE||A/582/CE/2009|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Francesco Burzotta, MD, PhD, Catholic University of Sacred Heart|
|Study Sponsor ICMJE||Catholic University of the Sacred Heart|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Catholic University of the Sacred Heart|
|Verification Date||January 2010|
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