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Safety Evaluation of Intracoronary Infusion of Extracellular Vesicles in Patients Following Coronary Stent Implantation

Phase 1
Active, not recruiting
Conditions
Percutaneous Coronary Intervention
Interventions
Registration Number
NCT04327635
Lead Sponsor
Christopher J. McLeod
Brief Summary

The purpose of this study is to determine the safety of using a biological drug called PEP in people who have had a coronary stent placed. A biological drug is a substance that is made from a living organism or its products (parts). In this case, PEP is made of certain parts of blood from living blood donors obtained from a certified blood bank. PEP comes in a powder form and is mixed with heparinized saline (a solution used to prevent clots in catheters) to create a solution that can be injected. The investigators want to see if PEP can be used to stop or slow heart damage.

Detailed Description

Patients who undergo Percutaneous Coronary Intervention (PCI) will be treated with a single dose of PEP within 20 minutes after stent placement or post-dilation (whichever is last). Subjects will be screened at the time of emergency room presentation. Subjects will be treated in the cardiac catheterization laboratory where the PCI will be completed and PEP will be administered. Subjects will be followed for one year after PEP administration through clinic visits.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
9
Inclusion Criteria
  • Undergoing ≥1 elective, urgent, or emergent coronary stent implantation
  • Angiographic evidence of TIMI 3 flow through the stented vessel after stent placement
  • Angiographic evidence of residual stenosis visually <30% after stent placement
  • Willing and able to provide signed informed consent
  • Lives within 90 mile radius of study site
  • Willing and able to return to study site for all follow-up visits
Exclusion Criteria
  • Prior solid organ transplantation at any time
  • Pregnant or lactating at screening
  • Known presence of chronic systemic inflammatory disorder that requires ongoing therapy with immunosuppressive agents
  • Known immune system compromise including but not limited to human immunodeficiency virus (HIV), hepatitis A, hepatitis B (HBV) or hepatitis C (HCV) infection
  • Known history of malignancy of any type except non-melanoma skin cancer
  • Known serum creatinine >2 mg/dL or GFR ≤30 mL/min within the last twelve months
  • Known AST, ALT, and/or bilirubin (total) elevated twice the upper limit of normal for age & gender within the last twelve months
  • Known Hemoglobin lower than 8.0 g/dL within the last twelve months
  • Known current illicit drug use at screening
  • Other major surgical procedure or major trauma within the previous 14 days prior to enrollment
  • Female of child bearing potential who is unwilling to agree to use acceptable contraception methods for 3 months after receiving the investigational drug
  • Pacemaker/ICD implant in place
  • Adult lacking decision-making capacity
  • Prisoner
  • Non-English speaking
  • English-speaking but illiterate
  • Legally blind
  • Known allergy to heparin or heparin-induced thrombocytopenia
  • Known history of positive SARS-CoV2 testing within the last 30 days
  • DNR/DNI status prior to PCI procedure or planned DNR/DNI status after PCI procedure
  • Homeless or no permanent address at the time of enrollment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
PEP in Coronary Stent ImplantationPEPPatients undergoing a percutaneous coronary intervention (PCI) and possible stent placement procedure will receive a one-time intracoronary infusion of PEP within 20 minutes after stent placement or post-dilation (whichever comes last).
Primary Outcome Measures
NameTimeMethod
Dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of a single dose (10 mL) of PEP at escalating concentrations of extracellular vesicles delivered at a single time point (after PCI).Days 1-14 of the study period for each study participant.

DLTs are defined as: signs of infection present in the judgement of a reviewing MD, CTCAE Grade 2 or higher bronchial stricture (rhonchi/wheezing), or CTCAE Grade 3 or higher defined as new or reoccurring angina or anginal equivalent after infusion with PEP; elevated ALT, AST, total or direct bilirubin, unless due to procedural complications or complications of ischemic cardiomyopathy (ICM); decreased hemoglobin or platelet level, unless due to procedural complications or complications of ICM; sustained ventricular arrhythmia during PEP infusion; hypersensitivity or anaphylaxis during PEP infusion; any other grade 3 or higher adverse event.

Secondary Outcome Measures
NameTimeMethod
Ejection fractionDay 7 and Day 40 of the study period for each study participant.

Cardiac MRI will be used to assess ejection fraction.

Infarction scar sizeDay 7 and Day 40 of the study period for each study participant.

Cardiac MRI will be used to assess myocardial infarction scar size.

Alloimmune ResponseDay 1 (Baseline/Screening) visit, Day 40 and Day 365

Class I \& II Antibody Single Antigen Bead testing will be completed. Changes will be documented and evaluated.

Trial Locations

Locations (1)

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

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