The TRansendocardial Stem Cell Injection Delivery Effects on Neomyogenesis STudy (The TRIDENT Study)

NCT02013674 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20120660
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Thirty (30) patients with chronic ischemic left ventricular dysfunction secondary to MI scheduled to undergo cardiac catheterization will be enrolled in the study. This is a phase II study intended to gain additional safety and efficacy assessments among two dose levels previously studied in a phase I setting.

Conditions

Chronic Ischemic Left Ventricular Dysfunction; Myocardial Infarction

Keywords

Cardiovascular; Chronic Ischemic Left Ventricular Dysfunction

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Serious Adverse Events (SAE).

  Incidence (at one month post-catheterization) of any treatment-emergent serious adverse events, defined as the composite of: death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 15 seconds or with hemodynamic compromise).

  One month post-catheterization

Secondary Outcomes (22)

• Infarct Scar Size (ISS)

  Baseline, 12 months

• Number of Participant With Reported Tissue Perfusion

  6 months, 12 months

• Peak Oxygen Consumption (VO2)

  Baseline, 6 months, 12 months

• Six-minute Walk Test.

  Baseline, 3 months, 6 months, 12 months

• Changed in New York Heart Association (NYHA) Functional Classification Based on Patient's Self Reported Activity Level.

  Baseline to 3 months, Baseline to 6 months, Baseline to 12 months

Study Arms (2)

Group 1: 20 million Allogeneic hMSCs

EXPERIMENTAL

Fifteen (15) patients to be treated with Allo-hMSCs: 4 million cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 0.2x 10\^8 (20 million) Allo-hMSCs.

Biological: Allogeneic hMSCs

Group 2: 100 million Allogeneic hMSCs

EXPERIMENTAL

Fifteen (15) patients to be treated with Allo-hMSCs: 20 million cells/ml delivered in a dose of 0.5 ml per injection x 10 injections for a total of 1x 10\^8 (100 million) Allo-hMSCs.

Biological: Allogeneic hMSCs

Interventions

Allogeneic hMSCs BIOLOGICAL

Allogeneic Adult Human Mesenchymal Stem Cells (MSCs) delivered via injection

Also known as: Allogeneic Adult Human Mesenchymal Stem Cells (MSCs)

Group 1: 20 million Allogeneic hMSCs; Group 2: 100 million Allogeneic hMSCs

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to participate in this study, a patient MUST:
• Be ≥ 21 and \< 90 years of age.
• Provide written informed consent.
• Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by previous myocardial infarction documented by an imaging study demonstrating coronary artery disease with corresponding areas of akinesis, dyskinesis, or severe hypokinesis.
• Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensin-converting enzyme inhibition, the patient must have been on a stable dose of a clinically appropriate agent for 1 month.
• Be a candidate for cardiac catheterization within 5 to 10 weeks of screening as determined by doctors.
• Have an ejection fraction of less than or equal to 50% by gated blood pool scan, two-dimensional echocardiogram, CT, or left ventriculogram within the prior six months and not in the setting of a recent ischemic event.

You may not qualify if:

• In order to participate in this study, a patient MUST NOT:
• Have a baseline glomerular filtration rate ≤ 35 ml/min/1.73m2.
• Have a known, serious radiographic contrast allergy.
• Have a Mechanical aortic valve or heart constrictive device.
• Have a documented presence of aortic stenosis (aortic stenosis graded as 1.5cm2 or less).
• Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
• Require coronary artery revascularization. Patients who require or undergo revascularization procedures should undergo these procedures a minimum of 3 months in advance of treatment in this study. In addition, patients who develop a need for revascularization following enrollment will be submitted for this therapy without delay.
• Have evidence of a life-threatening arrhythmia in the absence of a defibrillator (non-sustained ventricular tachycardia ≥ 20 consecutive beats or complete second or third degree heart block in the absence of a functioning pacemaker) or Corrected for heart rate (QTc) interval \> 550 ms on screening ECG
• Automatic Implantable Cardioverter Defibrillator (AICD) firing in the past 60 days prior to enrollment.
• Have a hematologic abnormality as evidenced by hematocrit \< 25%, white blood cell \< 2,500/µl or platelet values \< 100,000/µl without another explanation.
• Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the upper limit of normal (ULN).
• Have a coagulopathy = (INR \> 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR \< 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment
• Have known allergies to penicillin or streptomycin.
• Hypersensitivity to Dimethyl Sulfoxide (DMSO).
• Be an organ transplant recipient.

Sponsors & Collaborators

• Joshua M Hare: lead
• The Emmes Company, LLC: collaborator

Study Sites (1)

ISCI / University of Miami

Miami, Florida, 33136, United States

Location

Related Publications (1)

• Florea V, Rieger AC, DiFede DL, El-Khorazaty J, Natsumeda M, Banerjee MN, Tompkins BA, Khan A, Schulman IH, Landin AM, Mushtaq M, Golpanian S, Lowery MH, Byrnes JJ, Hendel RC, Cohen MG, Valasaki K, Pujol MV, Ghersin E, Miki R, Delgado C, Abuzeid F, Vidro-Casiano M, Saltzman RG, DaFonseca D, Caceres LV, Ramdas KN, Mendizabal A, Heldman AW, Mitrani RD, Hare JM. Dose Comparison Study of Allogeneic Mesenchymal Stem Cells in Patients With Ischemic Cardiomyopathy (The TRIDENT Study). Circ Res. 2017 Nov 10;121(11):1279-1290. doi: 10.1161/CIRCRESAHA.117.311827. Epub 2017 Sep 18.

  PMID: 28923793 BACKGROUND

Related Links

• Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine

MeSH Terms

Conditions

Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Results Point of Contact

• Title: Marietsy pujol / Senior Regulatory Specialist
• Organization: ISCI / University of Miami Miller School of Medicine

mpujol@med.miami.edu

305-243-7273

Study Officials

• Joshua M Hare, MD

  ISCI / University of Miami Miller School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Science Officer, Director of Interdisciplinary Stem Cell Institute

Study Record Dates

• First Submitted: December 2, 2013
• First Posted: December 17, 2013
• Study Start: February 13, 2014
• Primary Completion: March 2, 2017
• Study Completion: September 18, 2017
• Last Updated: February 11, 2020
• Results First Posted: February 5, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)