BLADE-PCI Trial (BLADE); PHASE IIB LIPOSOMAL ALENDRONATE STUDY

NCT02645799 | Unknown Phase 2 DMC

• 1 other identifier: LA-II-02
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to assess the safety, efficacy and dose response of LABR-312 administered intravenously at the time of percutaneous coronary intervention (PCI) with a drug eluting stent in reducing restenosis as measured by Optical Coherence Tomography (OCT) at 9 months post procedure in patients with diabetes mellitus (DM). Administration of LABR-312 at the time of PCI will reduce restenosis compared with placebo as assessed by the OCT endpoint of % neointimal hyperplasia (%NIH) volume at 9 months in patients with DM.

Conditions

Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• %NIH volume

  NIH volume/stent volume × 100 at 9 months as measured by the OCT core laboratory (all doses pooled vs. placebo).

  at 9 months

Secondary Outcomes (23)

• %NIH at minimum lumen area (MLA) site

  9 months

• MLA

  9 months

• % area stenosis

  9 months

• % stent strut coverage

  9 months

• In-stent late loss

  9 months

Study Arms (2)

LABR-312

ACTIVE COMPARATOR

LABR-312 will be administered intravenously at the time of percutaneous coronary intervention (PCI) with a drug eluting stent. Target lesions will be treated with the Resolute Integrity Drug Eluting Stent during the index PCI. Three (3) doses will be tested: Group 1: Low dose -\> 0.01 mg LABR-312 Group 2: Intermediate dose-\> Up to 0.03 mg LABR-312 Group 3: High dose-\> Up to 0.08 mg LABR-312 The duration of subject participation will be 1 year; clinical follow-up will be performed at 30 days, 9 months, and 1 year post randomization. OCT follow-up will be performed at 9 months.

Drug: LABR-312

saline

PLACEBO COMPARATOR

Placebo will be administered intravenously at the time of percutaneous coronary intervention (PCI) with a drug eluting stent. Target lesions will be treated with the Resolute Integrity Drug Eluting Stent during the index PCI. Three (3) doses will be tested: Group 1: Low dose -\> placebo (saline) equivalent to 0.01 mg LABR-312. Group 2: Intermediate dose-\> placebo (saline) equivalent to up to 0.03 mg LABR-312 Group 3: High dose-\> placebo (saline) equivalent to up to 0.08 mg LABR-312. The duration of subject participation will be 1 year; clinical follow-up will be performed at 30 days, 9 months, and 1 year post randomization. OCT follow-up will be performed at 9 months.

Drug: Saline (placebo)

Interventions

LABR-312 DRUG

administered intravenously at the time of percutaneous coronary intervention (PCI) with a drug eluting stent

LABR-312

Saline (placebo) DRUG

administered intravenously at the time of percutaneous coronary intervention (PCI) with a drug eluting stent

saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has medically treated diabetes mellitus (is on insulin or oral or injectable hypoglycemic medications).
• Patient is eligible and has an indication for PCI with a drug eluting stent (patient may be consented prior to diagnostic angiography with possible PCI).
• Patient presents with angina (stable or unstable), silent ischemia (in absence of symptoms must have a positive stress test, FFR ≤0.80, or angiographic stenosis of ≥70%), NSTEMI, or recent STEMI (\>7 days from procedure).
• Non-target vessel PCI are allowed prior to randomization depending on the time interval and conditions as follows:
• During Baseline Procedure:
• PCI of non-target vessels performed during the baseline procedure itself immediately prior to randomization, if successful and uncomplicated, defined as: \<50% visually estimated residual diameter stenosis, TIMI Grade 3 flow, no dissection ≥ NHLBI type C, no perforation, no persistent ST segment changes, no prolonged chest pain, no TIMI major or BARC type 3 bleeding.
• Less than 24 hours prior to Baseline Procedure:

You may not qualify if:

• hours-30 days prior to Baseline Procedure:
• PCI of non-target vessels 24 hours to 30 days prior to randomization if successful and uncomplicated as defined above.
• In cases where non-target lesion PCI has occurred 24-72 hours prior to the baseline procedure, at least 2 sets of cardiac biomarkers must be drawn at least 6 and 12 hours after the non-target vessel PCI.
• If cardiac biomarkers are initially elevated above the local laboratory upper limit of normal, serial measurements must demonstrate that the biomarkers are falling.
• Over 30 days prior to Baseline Procedure:
• PCI of non-target vessels performed greater than 30 days prior to procedure whether or not successful and uncomplicated.
• All non-target lesions (i.e. those not meeting angiographic criteria for the study) should be treated prior to randomization. All target lesions must be planned to be treated during the index procedure. The investigator will declare which target lesions are intended for treatment at the time of randomization. In the event that all target lesions cannot be treated (e.g. due to contrast load), staged procedure should be delayed preferably at least 2 weeks after the index PCI, and those lesions will be considered non-target lesions. Any such planned staged lesions must be declared at the end of the index procedure.
• Prior target-vessel PCI is allowed if it occurred ≥6 months prior to randomization and no restenosis is present, or if re-intervention is planned on the restenotic lesion(s) as a non-target lesion.
• The patient or legal guardian is willing and able to provide written informed consent and comply with follow-up visits and the testing schedule.
• Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥2.25mm to ≤4.2mm and diameter stenosis ≥50% to \<100%.
• Thrombolysis in Myocardial Infarction (TIMI) flow 2 or 3. If more than 1 target lesion will be treated, the reference vessel diameter and lesion length of each must meet the above criteria.
• STEMI within 7 days of presentation to the first treating hospital, whether a transfer facility or the study hospital
• PCI within the 24 hours prior to randomization
• Cardiogenic shock (defined as persistent hypotension \[systolic blood pressure \<90 mm Hg\] or requiring pressors or hemodynamic support, including IABP)
• Known left ventricular ejection fraction \<30%

Sponsors & Collaborators

• BIOrest Ltd.: lead

Study Sites (1)

Kaplan Medical Center

Rehovot, Israel

Location

Related Publications (1)

• Genereux P, Chernin G, Assali AR, Peruga JZ, Robinson SD, Schampaert E, Bagur R, Mansour S, Rodes-Cabau J, McEntegart M, Gerber R, L'Allier P, de Silva R, Daneault B, Aggarwal SK, Dzavik V, Ozan MO, Ben-Yehuda O, Maehara A, Stone GW, Jonas M. Double-blind, placebo-controlled evaluation of biorest liposomal alendronate in diabetic patients undergoing PCI: The BLADE-PCI trial. Am Heart J. 2022 Jul;249:45-56. doi: 10.1016/j.ahj.2022.03.004. Epub 2022 Mar 17.

  PMID: 35305955 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Philippe Généreux, MD

  Cardiovascular Research Foundation (CRF)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2015
• First Posted: January 5, 2016
• Study Start: April 1, 2016
• Primary Completion: August 1, 2018
• Study Completion: November 1, 2018
• Last Updated: January 11, 2018

Record last verified: 2018-01

Locations

IL (1)