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

Phase 1
Conditions
Heart Failure With Reduced Ejection Fraction
Interventions
Device: VB-C01
Registration Number
NCT03746938
Lead Sponsor
Viscofan
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
10
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
VB-C01VB-C01Surgical 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.
Primary Outcome Measures
NameTimeMethod
Composite safety endpoint formed by the major adverse cardiac and cerebrovascular events (MACCE) occurring on all visits during the first year after implantation.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.

Secondary Outcome Measures
NameTimeMethod
Incidence of all-cause deathDuring the first year after implantation
Incidence of cardiovascular deathDuring the first year after implantation
Incidence of re-infarctionDuring the first year after implantation
Incidence of need for revascularizationDuring the first year after implantation
Incidence of hospitalization for heart failureDuring the first year after implantation
Incidence of sustained ventricular tachycardiaDuring the first year after implantation
Incidence of ventricular fibrillationDuring the first year after implantation
Incidence of strokeDuring the first year after implantation
Incidence of surgical complicationsDuring the first year after implantation
Changes in the pericardial physiologyDuring the first year after implantation

Assessed by echocardiography or MRI

VT inducibilityDuring the first year after implantation

Heterogeneous tissue on MRI as well as the presence of late potentials on the electrophysiological study scheduled at 1 year of follow-up.

Changes in DSA-HLADuring the first year after implantation
Changes in proinflammatory cytokinesDuring the first year after implantation
Changes in immunological cell types.During the first year after implantation
Changes in end-systolic volumeDuring the first year after implantation

Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in end-diastolic volumeDuring the first year after implantation

Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in left ventricular ejection fractionDuring the first year after implantation

Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in sphericity indexDuring the first year after implantation

Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in segmental contraction score (normal / hypokinetic / akinetic / dyskinetic) in the 17 myocardial segmentsDuring the first year after implantation

Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in systolic thickening by myocardial segmentsDuring the first year after implantation

Measured by echocardiography comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in the scar size expressed in gramsDuring the first year after implantation

Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in the viable myocardial mass expressed in gramsDuring the first year after implantation

Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in the scar size expressed in percentage of LVDuring the first year after implantation

Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in the percentage of viable myocardium in LVDuring the first year after implantation

Measured by MRI comparing the baseline study of each patient with the studies performed in that same patient during the follow-up.

Changes in the functional classDuring the first year after implantation

According to the New York Heart Association (NYHA) for dyspnea

Changes in the patient-perceived quality of lifeDuring the first year after implantation

According to the Minnesota Living with Heart Failure Questionnaire (MLHFQ)

Changes in the distance covered on the 6-minute walk testDuring the first year after implantation
Changes in the peak oxygen consumption on ergospirometryDuring the first year after implantation
Changes in the brain natriuretic peptideDuring the first year after implantation

Trial Locations

Locations (2)

Clínica Universidad de Navarra

🇪🇸

Pamplona, Navarra, Spain

Hospital General Universitario Gregorio Marañón

🇪🇸

Madrid, Spain

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