TRANSFORM OCT TRiple Assessment of Neointima Stent FOrmation to Reabsorbable polyMer With Optical Coherence Tomography

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2013 by A.O. Ospedale Papa Giovanni XXIII
Sponsor:
Information provided by (Responsible Party):
GGuagliumi, A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier:
NCT01972022
First received: October 24, 2013
Last updated: NA
Last verified: October 2013
History: No changes posted
  Purpose

First prospective randomized controlled study to evaluate in an 'all-comers' population with coronary artery disease whether treatment with a novel everolimus eluting stent (EES) with a biodegradable polymer is superior to a durable polymer zotarolimus eluting stent (ZES), with respect to the long term vascular response to treatment These data are important to ascertain the superiority of a new generation DES with bioabsorbable polymer coating to reduce the long term development of in-stent neoatherosclerosis.


Condition Intervention Phase
Coronary Artery Lesions
Stent Healing With Novel Bioabsorbable Polymer EES
Device: EES SYNERGY™
Device: ZES, RESOLUTE Integrity™
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Optical Coherence Tomography (OCT) Study on Coronary Vessel Wall Response to Stent Eluting Everolimus From a Biodegradable Polymer (EES SYNERGY™) Compared With Stent Eluting Zotarolimus From a Durable Polymer (ZES, RESOLUTE Integrity™).

Further study details as provided by A.O. Ospedale Papa Giovanni XXIII:

Primary Outcome Measures:
  • percentage of frames with in stent-lipid laden neointima, neovascularization, calcification and thin-cap fibro-atheroma (TFCA) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    OCT finding of neoatherosclerosis, counted as percentage of frames with in stent-lipid laden neointima, neovascularization, calcification and thin-cap fibro-atheroma (TFCA) (18 month primary end-point)

  • length of consecutive frames with uncovered struts [ Time Frame: 3 and 18 months ] [ Designated as safety issue: Yes ]
    OCT derived maximum length of consecutive frames with uncovered struts in the two stent arms at 3 and 18 month (3 month primary end-point and 18 months co-primary end-points)


Secondary Outcome Measures:
  • percent well apposed struts at implant without neointima [ Time Frame: 3 and 18 months ] [ Designated as safety issue: Yes ]
    OCT derived proportion of well apposed struts at implant without neointima (% uncovered struts) at 3 and 18 months

  • Acquired stent malapposition [ Time Frame: 3 and 18 moths ] [ Designated as safety issue: Yes ]
    Number and extent (max area-volume) of newly acquired malapposed struts at 3 and 18 months.

  • OCT derived abnormal intraluminal tissue [ Time Frame: 3 and 18 months ] [ Designated as safety issue: Yes ]
    Presence of any abnormal intraluminal protruding mass at 3 and 18 months

  • percentage OCT frames with uncovered struts [ Time Frame: 3 and 18 months ] [ Designated as safety issue: Yes ]
    Number/percentage of OCT frames with > 30% uncovered struts at 3 and 18 months

  • Neointimal tissue thickness [ Time Frame: 3 and 18 months ] [ Designated as safety issue: Yes ]
    OCT calculated thickness of tissue covering stents at 3 and 18 months

  • OCT derived percentage of frames with mature neointima [ Time Frame: 3 and 18 months ] [ Designated as safety issue: Yes ]
    Percentage of frames with evidence of mature neointimal coverage in the two stent arms

  • OCT derived tissue heterogeneity in neointima deposition [ Time Frame: 3 and 18 moths ] [ Designated as safety issue: Yes ]
    Segmental tissue heterogeneity in neointima deposition across the entire stent length (as assessed by OCT tissue properties parameters - including normalized intensity, attenuation, tissue contrast) at 3 and 18 months


Estimated Enrollment: 90
Study Start Date: November 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EES SYNERGY™
coronary artery lesions treated with Bioabsorbable Polymer EES
Device: EES SYNERGY™
percutaneous coronary intervention with implantation of Bioabsorbable Polymer EES
Active Comparator: ZES, RESOLUTE Integrity™
coronary artery lesions treated with ZES, RESOLUTE Integrity™ stent system
Device: ZES, RESOLUTE Integrity™
percutaneous coronary intervention using ZES, RESOLUTE Integrity™ coronary stent

Detailed Description:

During the last decade a considerable clinical experience has been accumulated with the use of drug eluting coronary stents with durable polymers, that permanently cover the metallic stent scaffold, allowing the local delivery of anti-restenotic agents. However durable polymers have been associated with an increased risk of late and very late stent thrombosis and the anticipated development of in stent neo-atherosclerosis. Since permanent polymer coatings may have pro-inflammatory effects, with delayed healing and prolonged endothelial dysfunction, current research on DES has focused on the use of biodegradable polymer coatings, which disappear after a short period of drug-release (3-4 months). Current clinical guidelines recommend at least 6-12 months of dual antiplatelet therapy (DAPT) after DES implantation,in order to prevent ST. Recent data obtained by pooled analyses of ZES, support a significant reduction of the DAPT to the same range used with bare metal stents. The substantial delays in DES healing observed from multiple human pathology series and in-vivo studies using Optical Coherence Tomography (OCT) were not assessed as risk factors for prolonged used of DAPT. However different patient cohorts might have different responses to stent implantation. In addition, there is no comparative evidence on long term development of neo-atherosclerosis in bioabsorbable versus permanent polymer DES. OCT allows precise assessment of stent strut apposition and coverage and accurate measures of different tissue components of neoatherosclerosis. This study is the first attempting to characterize the early and late vascular responses to novel bioabsorbable polymer EES (SYNERGY™) compared with a permanent polymer benchmark novel generation ZES (RESOLUTE INTEGRITY™) .The stent comparator has been selected due to the large use across the interventional cardiology community and the recent approval from European Regulators Authorities to update the CE (Conformité Européenne) mark labeling to only one-month duration of dual anti-platelet therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is ≥18 years of age;
  2. Subject has stable angina or acute coronary syndrome (including acute myocardial infarction) with evidence of coronary ischemia and de novo atherosclerotic coronary artery disease in multiple vessels with an indication for stent implantation;
  3. Target lesion stenosis is ≥ 70% (visual estimate)
  4. All target lesions require treatment with stents having diameters from 2.25 mm to 4.0 mm (visual estimate)
  5. Target lesion length ≥10 mm and ≤34 mm for each target lesion(s)
  6. Subject must sign Ethics Committee approved informed consent prior to undergoing any study specific procedure;
  7. Subject must be willing and able to comply with specified follow-up schedule.

Exclusion Criteria:

  1. Unprotected left main coronary disease;
  2. Chronic total occlusion;
  3. Severe calcified target lesion(s) which cannot be, in the investigator's opinion, successfully treated;
  4. Significant angulation in the target vessel that, in the Investigator's opinion, may preclude stent delivery and deployment;
  5. Bifurcation disease involving a side branch ≥ 2.5 mm in diameter;
  6. Restenotic lesions;
  7. Target lesion(s) within a coronary bypass graft (e.g., saphenous vein or arterial graft);
  8. In the Investigator's opinion, the lesion is not suitable for stenting or OCT imaging (e.g. extreme tortuosity, very distal lesions).
  9. Documented left ventricular ejection fraction ≤30%;
  10. Serum creatinine > 2.0 mg/dl at the time of treatment;
  11. Recipient of heart transplant;
  12. Subject with malignancies or other comorbidities (i.e. severe liver, renal, pulmonary, pancreatic disease) with life expectancy less than 18 months or that may results in protocol non-compliance;
  13. Known bleeding or hyper-coagulable disorder;
  14. Known allergy to stent components or any antiplatelet recommended drug
  15. Planned medical or surgical procedures requiring modification of DAPT regimen within 3 months after the index procedure;
  16. Women of childbearing potential without negative pregnancy test within 7 days before enrollment
  17. Currently participating in an investigational study that has not completed the primary endpoint or that clinically interferes with the study endpoints
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01972022

Contacts
Contact: Monia Lorini, MD 0352673341 ext +39 mlorini@hpg23.it

Locations
Italy
A.O. Ospedale Papa Giovanni XXIII Not yet recruiting
Bergamo, Italy, 24127
Contact: Vasile Sirbu, MD    0352673446 ext +39    dr_sarbu@yahoo.com   
Sponsors and Collaborators
A.O. Ospedale Papa Giovanni XXIII
Investigators
Principal Investigator: Giulio Guagliumi, MD A.O. Papa Giovanni XXIII, Cardiovascular Department
  More Information

No publications provided

Responsible Party: GGuagliumi, MD, A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier: NCT01972022     History of Changes
Other Study ID Numbers: TRANSFORM 1207/2013
Study First Received: October 24, 2013
Last Updated: October 24, 2013
Health Authority: Italy: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by A.O. Ospedale Papa Giovanni XXIII:
Drug Eluting Stents
Bioabsorbale Polymer Coating
Neoatherosclerosis
Stent Coverage
Stent Failure

ClinicalTrials.gov processed this record on July 23, 2014