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Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth

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ClinicalTrials.gov Identifier: NCT00349895
Recruitment Status : Completed
First Posted : July 10, 2006
Last Update Posted : April 8, 2014
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

This is a multi-center, prospective, non-randomized study. Approximately 90 patients from up to 16 centers will be entered in the study. Patients will be followed clinically for up to 5 years post-procedure. All patients will have a repeat angiography at 6 months follow-up.

The primary objective of this study is to evaluate the safety and effectiveness of the Genous Bio-engineered R stentTM in conjunction with optimal statin therapy (80mg of atorvastatin), in the treatment of elective patients with up to two de novo native coronary artery lesions. The Genous stent received CE mark for the intended indication in August 2005


Condition or disease Intervention/treatment Phase
Coronary Artery Disease Coronary Artery Stenosis Device: Coronary stent implantation Phase 4

Detailed Description:

Currently available coronary stents are prone to thrombosis and restenosis. It is believed that the accelerated re-establishment of a functional endothelial layer on damaged stented vascular segments may help to prevent potentially serious complications by providing a barrier to circulating cytokines, and by the ability of endothelial cells to produce substances that passivate the underlying smooth muscle cell layer.

By recruiting the patient's own EPCs to the site of vascular injury (e.g. the site of a coronary stent implant), an acceleration of the normal endothelialization process would occur. It is theorized that the rapid establishment of a functioning endothelial layer may promote the transformation of the injured site to a healthy state. For example, in the case of coronary stent implantation, rapid re-endothelialization may reduce inflammation, thrombosis and potentially eliminate restenosis.

The influences of EPC recruitment and reendothelialization on restenosis range from the effects on the vascular repair response, to the prevention of platelet aggregation and activation, angiogenesis, and enhancement of vasomotor response. Recently it has been shown that the integrity and functional activity of the endothelial monolayer play a crucial role in the prevention of atherosclerosis. However, risk factors for coronary artery disease such as age, hypertension, hypercholesterolemia, and diabetes reduce the number and functional activity of these circulating EPCs, thus limiting the regenerative capacity. The impairment of stem cells by risk factors in CAD patients may contribute to the limited regenerative capacity of diseased endothelium, as well as to atherogenesis and atherosclerotic disease progression. Therefore, relating the number and function of circulating EPCs to the functional outcome of stent technology is crucial to identify a beneficial effect on in-stent restenosis formation and vascular (dys) function.

The HEALING FIM and HEALING II clinical studies sought to define the safety and efficacy of a stent designed to sequester circulating endothelial progenitor cells to the luminal surface of the stent struts by an anti-CD34 antibody coating, thereby promoting reendothelialization of the coronary stent and the vascular healing response following stent deployment. Enhanced vascular healing will reinstate vascular integrity, prevent platelet aggregation and sub-acute in-stent thrombosis, reinstate vasoreactivity and inhibit restenosis formation. In the HEALING II study, a correlation was found between EPC levels and angiographic/IVUS outcomes in patients receiving the Genous stent. Patients with normal EPC titers had significantly less in-stent late loss compared to those with low EPCs (0.53 vs 1.02mm). This is consistent with the results from drug eluting stent trials, thereby establishing proof of concept of the EPC capturing technology, provided adequate EPC target cell population is available.

There are several animal studies demonstrating that statin therapy was associated with a 2.5 to 3 fold increase of circulating EPCs leading to accelerated reendothelialization, vascular repair and improved angiogenesis. In addition, Dimmeler and co-workers found similar results in a small cohort of cardiovascular patients receiving atorvastatin therapy (n=7, Circulation 2001), suggesting an angiotrophic effect of atorvastatin therapy in addition to its previously defined pleiotrophic properties. Similarly, Drexler and co-workers described similar EPC recruiting properties of simvastatin in CAD patients unrelated to/ irrespective of LDL reduction (n=10, Circulation 2005).

The current study seeks to confirm the safety and optimize the effectiveness of the EPC capture technology (Genous Bio-engineered R stent) by incorporating a high dose statin therapy, specifically atorvastatin 80mg, for at least two weeks prior to the index procedure.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth. A Clinical, Multi-center, Prospective, Non-Randomized Study
Study Start Date : August 2006
Primary Completion Date : January 2008
Study Completion Date : January 2012
Arms and Interventions

Intervention Details:
    Device: Coronary stent implantation
    Percutaneous Coronary Intervention

Outcome Measures

Primary Outcome Measures :
  1. The primary endpoint of this study is in-stent late loss by Quantitative Coronary Angiography (QCA). [ Time Frame: at 6 months ]

Secondary Outcome Measures :
  1. Angiographic success. [ Time Frame: during procedure ]
  2. Procedure success. [ Time Frame: during the index hospitalization ]
  3. Angiographic and/or clinical stent thrombosis. [ Time Frame: Up to 5 years ]
  4. In-stent late loss [ Time Frame: at 18 months. ]
  5. Binary restenosis rate [ Time Frame: at 6 and 18 months. ]
  6. In-segment late loss. [ Time Frame: at 6 and 18 months ]
  7. Volumetric assessment (derived from QCA parameters). [ Time Frame: at 6 and 18 months ]
  8. Circulating endothelial progenitor cell (EPC) count [ Time Frame: at screening, index procedure and at 30 days. ]
  9. Target Vessel Failure (TVF) [ Time Frame: at 30 days, 6, 12, 18 months and at 2, 3, 4 and 5 years. ]
  10. Major adverse cardiac events (MACE) [ Time Frame: at 30 days, 6, 12, 18 months and at 2, 3, 4 and 5 years. ]
  11. Clinically-driven Target Lesion Revascularization (TLR) free rate [ Time Frame: at 30 days, 6, 12 and 18 months and at 2, 3, 4 and 5 years. ]
  12. Protocol related serious adverse events (SAEs) [ Time Frame: up to 5 years. ]
  13. Change in human anti-murine antibody (HAMA) plasma levels [ Time Frame: at 1 and 6 months follow-up as compared to baseline. ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 to 85 years of age;
  2. Symptomatic ischemic heart disease (CCS class 1-4, Braunwald class IB, IC, and/or objective evidence of myocardial ischemia);
  3. Treatment of 1 or 2 de novo lesions;
  4. Target lesion(s) is(are) located in a native coronary artery, which can be covered by one single stent of maximum 33 mm; The coronary artery lesion should be ≤27 mm in length (a margin of 3mm proximal and 3mm distal is recommended) and should be entirely covered by one single Genous Bio-engineered R stentTM . If predilation of the lesion is visually deemed necessary it should be performed prior to measuring the length of the lesion.
  5. Reference vessel diameter ≥ 2.5 and ≤ 3.75 mm by visual estimate;
  6. Acceptable candidate for coronary artery bypass surgery (CABG);
  7. Target lesion stenosis is ≥50% and <100% (minimum TIMI flow I at the time of the PCI procedure) (visual estimate);
  8. The patient is willing to comply with the specified follow-up evaluation;
  9. The patient has been informed of the nature of the study agrees to its provisions and has provided written informed consent, approved by the appropriate Ethics Committee (EC).

Exclusion Criteria:

General exclusion criteria:

  1. Women who are pregnant or women of childbearing potential who do not use adequate contraception;
  2. A Q-wave or non-Q-wave myocardial infarction within 72 hours preceding the index procedure, unless the CK and CK-MB enzymes or Troponin levels are less than twice the Upper Normal Limit;
  3. Impaired renal function (creatinine > 3.0 mg/dl or 265 µmol/l);
  4. Any patient who has a platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3 or a WBC of < 3,000 cells/mm3;
  5. Documented or suspected liver disease (including laboratory evidence of hepatitis);
  6. Recipient of heart transplant;
  7. Any patient who previously received murine therapeutic antibodies and exhibited sensitization through the production of Human Anti-murine Antibodies (HAMA);
  8. Patient with a life expectancy less than the follow-up period (5 years);
  9. Known allergies to aspirin, clopidogrel bisulphate (Plavix®) and ticlopidine (Ticlid®), heparin, or stainless steel;
  10. Known side-effects (clinically demonstrated by biological tests, elevated CK and liver assessments) to statins and previous attempts to treat side-effects were unsuccessful;
  11. Any significant medical condition which in the Investigator's opinion may interfere with the patient's optimal participation in the study;
  12. Currently participating in an investigational drug or another device study that has not completed the primary endpoint, or subject to inclusion in another investigational drug or another device study during follow-up of this study;
  13. Patients currently undergoing chemotherapy or immunosuppressant therapy;
  14. Patients with known malignancy(ies).

    Angiographic exclusion criteria:

  15. Unprotected left main coronary artery disease with ≥ 50% stenosis;
  16. Ostial target lesion;
  17. Totally occluded target vessel (TIMI flow 0);
  18. Target lesion has excessive tortuosity unsuitable for stent delivery and deployment;
  19. Target lesion involves bifurcation class D & type G including a side branch ≥ 2.5mm in diameter (either stenosis of both main vessel and major side branch or stenosis of just major side branch) that would require stenting of diseased side branch;
  20. Angiographic evidence of thrombus in the target vessel;
  21. A significant (> 50%) stenosis proximal or distal to the target lesion;
  22. Impaired runoff in the treatment vessel with diffuse distal disease;
  23. Ejection fraction ≤ 30%;
  24. Pre-treatment with devices other than balloon angioplasty, although direct stenting is allowed;
  25. Prior stent within 5mm of target lesion;
  26. Intervention of another lesion within 6 months before or within the scheduled angiographic follow-up of the index procedure.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00349895


Locations
Austria
Medizinische Universitätsklinik
Graz, Austria, 8036
Belgium
OLV Ziekenhuis Aalst
Aalst, Belgium, 9300
AZ Middelheim
Antwerp, Belgium, 2020
University Hospital Antwerp
Edegem, Belgium, 2650
Virga Jesse Ziekenhuis
Hasselt, Belgium, 3500
France
Hôpital Henri Mondor
Creteil, France, 94010
Germany
Herzzentrum Bad Krozingen
Bad Krozingen, Germany, 79189
Herz- und Diabeteszentrum Nordrhein-Westfalen
Bad Oeynhausen, Germany, 32545
Internistische Klinik Dr. Müller
Munich, Germany, 81379
Netherlands
Academisch Medisch Centrum
Amsterdam, Netherlands, 1105 AZ
Amphia Ziekenhuis
Breda, Netherlands, 4818 CK
Sint Antonius Ziekenhuis
Nieuwegein, Netherlands, 3435 CM
Erasmus Medisch Centrum
Rotterdam, Netherlands, 3015 GD
United Kingdom
Kings College Hospital
London, United Kingdom, SE5 9RS
John Radcliflfe Hospital
Oxford, United Kingdom, OX3 9DU
Sponsors and Collaborators
OrbusNeich
Investigators
Principal Investigator: Patrick W Serruys, MD, PhD Erasmus MC
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: OrbusNeich
ClinicalTrials.gov Identifier: NCT00349895     History of Changes
Other Study ID Numbers: HEALING IIb
First Posted: July 10, 2006    Key Record Dates
Last Update Posted: April 8, 2014
Last Verified: April 2014

Keywords provided by OrbusNeich:
Percutaneous Transluminal Coronary Angioplasty
Stent implantation

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Coronary Stenosis
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases