First in Humans to Evaluate Collagen Patches With Stem Cells in Patients With Ischemic Left Ventricular Dysfunction (CARDIOMESH)

First Open-label Trial in Humans to Evaluate the Safety and Efficacy of Epicardial Delivery of Collagen Patches With Adipose-derived Stem Cells in Patients With Ischemic Heart Disease and Left Ventricular Dysfunction.

It´s a first open-label trial in humans to evaluate the safety and efficacy of epicardial delivery of collagen patches with adipose-derived stem cells in patients with ischemic heart disease and left ventricular dysfunction that remain symptomatic despite optimal medical treatment.

Study Overview

• Status: Unknown
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Device: VB-C01

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
    • Contact: Javier Bermejo Thomas; Phone Number: 915868290; Email: javier.bermejo@salud.madrid.org
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Not yet recruiting
      • Clinica Universidad de Navarra
      • Contact: Laura Ribillaga; Email: larribillaga@unav.es

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:

• Men and women aged ≥18 years and ≤80 years.
• LVEF ≤35% as assessed by echocardiography, confirmed by MRI if there are no contraindications for this procedure.
• History of revascularised or nonrevascularisable coronary artery disease as the cause of ventricular dysfunction.
• NYHA functional class III for dyspnea under optimal medical treatment.
• Ability to perform the exercise test with respiratory gas consumption. MVO2 should be ≥ 10 and ≤ 18 ml/kg/min in the exercise test.
• Ability to perform a 6-minute walk test > 100 m and ≤ 400 m.
• Haemodynamic stability (blood pressure > 100/40 mmHg, heart rate < 110 bpm and oxygen saturation at rest in room air > 95%).

Exclusion Criteria:

• Participation in another clinical trial within 30 days prior to inclusion.
• Prior treatment with cell or gene therapy.
• Diagnosis of acute myocardial infarction with 3 months prior to inclusion.
• Significant coronary artery disease eligible for revascularization.
• Significant valvular disease eligible for surgery.
• Presence of uncontrolled ventricular arrhythmias (VR or VF) at the time of implant surgery.
• Women who are pregnant or breastfeeding.
• Mental disease or psychological condition that impedes the subject from understanding the nature of the protocol and granting his/her consent.
• Advanced dementia according to the Barthel index.
• Active systemic infection.
• History of primary or acquired immunodeficiency or on immunosuppressive therapy (within 3 months prior to inclusion or if the need for immunotherapy is foreseeable at any time during the study follow-up).
• Tumour disease, except that eradicated at least 5 years prior to inclusion in the study and without receiving chest radiotherapy. Completely eradicated nonmelanoma skin tumours (at any time) not requiring chest chemotherapy or radiotherapy) are permitted.
• History of autoimmune disease.
• Stroke within 12 months prior to inclusion.
• Respiratory compromise or need for home oxygen therapy.
• Life expectancy of less than 1 year for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: VB-C01; Surgical technique: Via left lateral thoracotomy, the heart is lifted and supported on two deep pericardial points with 4-0 or 5-0 Prolene double arrmed suture. Each suture is passed through the reinforced frame of the collagen membrane containing the stem cells (VB-C01) and then tied, while the upper part of the patch is held with forceps. After securing the lower part of the pericardial layer, the heart is allowed to slowly recover its position with the pericardial cavity while the collagen membrane is mobilized to cover all of the target area. If necessary, some sutures can be used to fix the patch VB-C01 to the epicardial surface of the heart. Each suture is likewise passed through the reinforced frame of the membrane.

Device: VB-C01; Surgical implant of VB-C01 (Collagen membrane seeded with allogeneic stem cells isolated from adipose tissue, ADSC).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite safety endpoint formed by the major adverse cardiac and cerebrovascular events (MACCE) occurring on all visits during the first year after implantation.	MACCE include: all-cause death, cardiovascular death, re-infarction, need for revascularization, hospitalization for heart failure, sustained ventricular tachycardia, ventricular fibrillation, or stroke.	During the first year after implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of all-cause death		During the first year after implantation
Incidence of cardiovascular death		During the first year after implantation
Incidence of re-infarction		During the first year after implantation
Incidence of need for revascularization		During the first year after implantation
Incidence of hospitalization for heart failure		During the first year after implantation
Incidence of sustained ventricular tachycardia		During the first year after implantation
Incidence of ventricular fibrillation		During the first year after implantation
Incidence of stroke		During the first year after implantation
Incidence of surgical complications		During the first year after implantation
Changes in the pericardial physiology	Assessed by echocardiography or MRI	During the first year after implantation
VT inducibility	Heterogeneous tissue on MRI as well as the presence of late potentials on the electrophysiological study scheduled at 1 year of follow-up.	During the first year after implantation
Changes in DSA-HLA		During the first year after implantation
Changes in proinflammatory cytokines		During the first year after implantation
Changes in immunological cell types.		During the first year after implantation
Changes in end-systolic volume	Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in end-diastolic volume	Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in left ventricular ejection fraction	Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in sphericity index	Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in segmental contraction score (normal / hypokinetic / akinetic / dyskinetic) in the 17 myocardial segments	Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in systolic thickening by myocardial segments	Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in the scar size expressed in grams	Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in the viable myocardial mass expressed in grams	Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in the scar size expressed in percentage of LV	Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in the percentage of viable myocardium in LV	Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.	During the first year after implantation
Changes in the functional class	According to the New York Heart Association (NYHA) for dyspnea	During the first year after implantation
Changes in the patient-perceived quality of life	According to the Minnesota Living with Heart Failure Questionnaire (MLHFQ)	During the first year after implantation
Changes in the distance covered on the 6-minute walk test		During the first year after implantation
Changes in the peak oxygen consumption on ergospirometry		During the first year after implantation
Changes in the brain natriuretic peptide		During the first year after implantation

Collaborators and Investigators

• Sponsor: Viscofan
• Collaborators: Ministerio de Ciencia e Innovación, Spain
• Investigators: Principal Investigator: Francisco Jesús Fernández-Avilés Díaz, Hospital General Universitario Gregorio Marañon

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 13, 2018
• Primary Completion (ANTICIPATED): October 30, 2020
• Study Completion (ANTICIPATED): October 30, 2020

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 15, 2018
• First Posted (ACTUAL): November 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 20, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Ventricular Dysfunction, Left
• Other Study ID Numbers: CARDIOMESH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No