Clinical trial NCT00739466: Biorest Liposomal Alendronate With Stenting sTudy (BLAST)
Official title: Intravenous Liposomal Alendronate Infusion in Subjects Undergoing Bare Metal Coronary Stent Implantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Stenosis
Keywords: Liposomal Alendronate
Percutaneous coronary intervention
Coronary stenting
de novo stenotic lesions
Native coronary arteries
Restenosis
Bare metal stent
Presillion CoCr coronary stent
Lead sponsor: BIOrest Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baim Institute for Clinical Research
name: Cardiovascular Research Foundation, New York
name: Stanford University
First posted: 2008-08-21
Enrollment: 226
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to assess the safety and efficacy of Liposomal Alendronate in the treatment of de novo stenotic lesions in native coronary arteries in a population undergoing PCI with implantation of a bare metal stent.

Study hypothesis: Liposomal Alendronate will reduce in-stent restenosis as compared to placebo.

Detailed description: This is a Phase II dose-finding, randomized, multi-center, prospective, double blind clinical study. Subjects undergoing percutaneous coronary intervention (PCI) with the Presillion™ CoCr bare metal stent will be randomized into three groups and administered (in a single dose intravenously (IV) through a peripheral venous catheter) either: low dose Liposomal Alendronate of 0.001 mg, high dose Liposomal Alendronate of 0.01 mg, or placebo (IV saline infusion) on a 1:1:1 basis.

All subjects will undergo angiographic follow-up at 6 months and 110 subjects enrolled from pre-specified sites will undergo intravascular ultrasound (IVUS) at baseline and follow-up at 6 months.

Eligibility criteria: Inclusion Criteria:

1. Subject is eligible for percutaneous coronary intervention .
2. Subject is an acceptable candidate for coronary artery bypass graft surgery.
3. Subject has stable angina pectoris
4. Subject is a candidate for elective stenting of up to 2 lesions.

Exclusion Criteria:

General

1. Any planned elective surgery or percutaneous intervention within 6 months post-procedure.
2. A previous coronary interventional procedure of any kind within 30 days prior to the procedure.
3. Subject requires a staged procedure of either the target or any non-target vessel within 9 months post-procedure.
4. Any drug eluting stent (DES) deployment within the past 12 months.
5. Any planned drug eluting stent (DES) deployment during the procedure associated with this study or within 3 months following the index procedure.
6. Known hypersensitivity or contraindication to aspirin or clopidogrel or a sensitivity to contrast media, which cannot be adequately pre-medicated
7. Concurrent medical condition with a life expectancy of less than 12 months.
8. Documented left ventricular ejection fraction (LVEF) \< 25% at the most recent evaluation.
9. Evidence of ST elevated myocardial infarction (STEMI) or non-STEMI with troponin (cTn) levels greater than or equal to 3 times the normal limit at any time within 72 hours of the intended trial procedure.
10. History of cerebrovascular accident or transient ischemic attack in the last 6 months.
11. Leukopenia .
12. Neutropenia
13. Thrombocytopenia
14. Serum creatinine level \>2.5 mg/dl within 7 days prior to index procedure.
15. History of bleeding diathesis or coagulopathy or inability to accept blood transfusions.
16. Known hypersensitivity or contraindication to aspirin, heparin or bivalirudin, clopidogrel and ticlopidine, cobalt, nickel, L-605 Cobalt chromium alloy, Alendronate or sensitivity to contrast media, which cannot be adequately pre-medicated.
17. History of severe:Gastrointestinal disease,Immunodeficiency,Bone diseases

Angiographic Exclusion Criteria

1. Unprotected left main coronary artery disease (obstruction greater than 50% in the left main coronary artery that is not protected by at least one non-obstructed bypass graft to the LAD or Circumflex artery or a branch thereof).
2. Any previous stent placement within 15 mm (proximal or distal) of the target lesion(s).
3. Target vessel exhibiting lesions with greater than 60% diameter stenosis outside of a range of 5 mm proximal and distal to the target lesion(s) based on visual estimate or on-line QCA.
4. Target lesion(s) exhibiting an intraluminal thrombus (occupying \>50% of the true lumen diameter) at any time.
5. Lesion location that is aorto-ostial or within 5 mm of the origin of the left anterior descending (LAD) or left circumflex (LCX).
6. The target lesion(s) requires treatment with a device other than PTCA prior to stent placement (such as, but not limited to, directional coronary atherectomy, excimer laser, rotational atherectomy, etc.).
7. Target lesion(s) with side branches \> 2.0mm in diameter.
8. Target lesion(s) involving a bifurcation (either stenosis of both main vessel and major branch or stenosis of just major branch).
9. Target lesion(s) with severe calcification.
10. Target vessel exhibiting excessive tortuosity that may impede stent delivery and deployment at target lesion(s).
11. Target lesion(s) located in a native vessel distal to an anastomosis with a saphenous vein graft or a left/right internal mammary artery (LIMA/RIMA) bypass.

Primary outcomes:
measure: In-stent late loss: measured at 6 months post-procedure as determined by quantitative coronary angiography (QCA).
timeFrame: 6 months post-procedure
Secondary outcomes:
measure: Major Adverse Cardiac Events (MACE)
timeFrame: at 30, 180 and 360 days as well as yearly through 5 years post-procedure
Other outcomes:
Locations:
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Bnei Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Nahariya
country: Israel
facility: Western Galilee Hospital, Nahariya
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Poriya
country: Israel
facility: The Baruch Padeh Medical Center, Poriya
city: Ramat Gan
country: Israel
facility: Sheba Medical Center, Tel Hashomer
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
Study officials:
affiliation: The Tel Aviv Sourasky Medical Center
name: Prof Shmuel Banai, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Banai S, Finkelstein A, Almagor Y, Assali A, Hasin Y, Rosenschein U, Apruzzese P, Lansky AJ, Kume T, Edelman ER. Targeted anti-inflammatory systemic therapy for restenosis: the Biorest Liposomal Alendronate with Stenting sTudy (BLAST)-a double blind, randomized clinical trial. Am Heart J. 2013 Feb;165(2):234-40.e1. doi: 10.1016/j.ahj.2012.10.023. Epub 2012 Dec 11.