Biorest Liposomal Alendronate With Stenting sTudy (BLAST) (BLAST)

Intravenous Liposomal Alendronate Infusion in Subjects Undergoing Bare Metal Coronary Stent Implantation

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Stenosis
• Intervention / Treatment: Drug: Liposomal Alendronate; Drug: Liposomal Alendronate; Drug: Saline infusion (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.

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Hadera, Israel, 38100
    • Hillel Yaffe Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Haifa, Israel, 34362
    • Lady Davis Carmel Medical Center
  • Haifa, Israel, 31048
    • Bnei Zion Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Nahariya, Israel, 22100
    • Western Galilee Hospital, Nahariya
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Poriya, Israel, 15218
    • The Baruch Padeh Medical Center, Poriya
  • Ramat Gan, Israel, 52521
    • Sheba Medical Center, Tel Hashomer
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • The Tel Aviv Sourasky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: low dose; Liposomal Alendronate dose of 0.001 mg	Drug: Liposomal Alendronate; IV in a single low dose during the index procedure (coronary stent implantation) over 2 hours; Other Names: LA; Drug: Liposomal Alendronate; IV in a single high dose during the index procedure (coronary stent implantation) over 2 hours; Other Names: LA
EXPERIMENTAL: high dose; Liposomal Alendronate dose of 0.01 mg	Drug: Liposomal Alendronate; IV in a single low dose during the index procedure (coronary stent implantation) over 2 hours; Other Names: LA; Drug: Liposomal Alendronate; IV in a single high dose during the index procedure (coronary stent implantation) over 2 hours; Other Names: LA
PLACEBO_COMPARATOR: placebo; IV saline infusion	Drug: Saline infusion (placebo); IV saline infusion during the index procedure (coronary stent implantation) over 2 hours; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
In-stent late loss: measured at 6 months post-procedure as determined by quantitative coronary angiography (QCA).	6 months post-procedure

Secondary Outcome Measures

Outcome Measure	Time Frame
Major Adverse Cardiac Events (MACE)	at 30, 180 and 360 days as well as yearly through 5 years post-procedure

Collaborators and Investigators

• Sponsor: BIOrest Ltd.
• Collaborators: Stanford University; Cardiovascular Research Foundation, New York; Baim Institute for Clinical Research
• Investigators: Principal Investigator: Prof Shmuel Banai, MD, The Tel Aviv Sourasky Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: August 20, 2008
• First Submitted That Met QC Criteria: August 20, 2008
• First Posted (ESTIMATE): August 21, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 17, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Percutaneous coronary intervention; Restenosis; Bare metal stent; de novo stenotic lesions; Liposomal Alendronate; Coronary stenting; Native coronary arteries; Presillion CoCr coronary stent
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Coronary Stenosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Alendronate
• Other Study ID Numbers: LA-II-01