Biorest Liposomal Alendronate With Stenting sTudy (BLAST)

Phase 2

Completed

• Conditions: Coronary Artery Stenosis
• Interventions: Drug: Liposomal Alendronate; Drug: Saline infusion (placebo)

• Registration Number: NCT00739466
• Lead Sponsor: BIOrest Ltd.

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.

Study Timeline

• Study First Submitted: 2008-08-20
• Study First Submitted QC: 2008-08-20
• Study First Posted: 2008-08-21
• Study Start: 2008-09
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-17
• Last Update Posted: 2016-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 226

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
low dose	Liposomal Alendronate	Liposomal Alendronate dose of 0.001 mg
high dose	Liposomal Alendronate	Liposomal Alendronate dose of 0.01 mg
placebo	Saline infusion (placebo)	IV saline infusion

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (12)

Western Galilee Hospital, Nahariya; 🇮🇱 Nahariya, Israel

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

Meir Medical Center; 🇮🇱 Kfar Saba, Israel

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

Sheba Medical Center, Tel Hashomer; 🇮🇱 Ramat Gan, Israel

The Baruch Padeh Medical Center, Poriya; 🇮🇱 Poriya, Israel

Kaplan Medical Center; 🇮🇱 Rehovot, Israel

The Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Bnei Zion Medical Center; 🇮🇱 Haifa, Israel

Hillel Yaffe Medical Center; 🇮🇱 Hadera, Israel

Lady Davis Carmel Medical Center; 🇮🇱 Haifa, Israel