Retrograde Application of Bone Marrow Aspirate Concentrate (Retro)

Retrograde Application of Bone Marrow Aspirate Concentrate (BMAC) Through Coronary Sinus in Patients With Congestive Heart Failure of Ischemic Etiology

The aim of our prospective randomised study is to assess the efficacy of the retrograde application of non-selected bone marrow autologous cells concentrate (BMAC) in patients with heart failure with reduced ejection fraction of left ventricle (HFREF) of ischemic aetiology. The evaluated preparation is concentrated BMAC, obtained using Harvest SmartPReP2 technology.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: BMAC

Detailed Description

Our assumption is that non-selected BMAC administrations will lead to improvements in the left ventricular ejection fraction (LV EF), the left ventricular end-systolic and end-diastolic diameters and volumes (measured with magnetic resonance imaging) compared to standard heart failure therapy.

Furthermore, it will be associated with improved exercise tolerance in the six-minute corridor walk test and an improvement in the life quality of patients without increasing the incidence of severe ventricular arrythmias.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Moravian-Silesian Region
    • Ostrava-Poruba, Moravian-Silesian Region, Czechia, 708 52
      • University Hospital Ostrava

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with chronic heart failure and left ventricular ejection fraction ≤ 40% with coronary artery disease and with symptoms of heart failure in the NYHA class ≥ 3 on standard heart failure therapy for 3 months and in a stabilised state for at least 1 month
• Age ≥18 years
• Informed, written consent by the patient
• Ability to comply fully with the study protocol
• Negative pregnancy test (and effective contraception) in women with childbearing potential

Exclusion Criteria:

• Previous bone marrow disease (especially myelodysplastic syndrome or non-Hodgkin's lymphoma)
• Acute myocardial infarction ˂ 1 week
• Active infection or antibiotics treatment ˂ 1 week
• Previous malingant ventricular arrhythmias without cardioverter-defibrilator (ICD) implantation
• Anemia (HTC≤28%), leukocythosis (≥ 14.000/mm3) or thrombocytopenia (≤50.000/mm3)
• Previous bleeding diathesis
• Need for hematopoietic growth factor treatment (e.g. erythropoetin, G-CSF)
• Impossibility of aspiration 240ml of bone marrow
• Hepathopathy or cirrhosis (bilirubin, ALT or AST ≥ 2,5x upper limit of normal)
• Terminal renal insufficiency or haemodyalysis
• Uncontrolled hypertension
• Need for high dose (> 7.5mg/day) corticotherapy within the next 6 months
• Inability to stop anticoagulation therapy (>72 hours) before bone marrow aspiration
• Known malignancies requiring actino or chemotherapy, or previous actinotherapy
• Patients with a BMI >40
• Known allergy to contrast agents
• Other comorbidities with a life expectancy of 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bone marrow autologous cells concentrate (BMAC); retrograde administration on non-selected BMAC via coronary sinus	Drug: BMAC; retrograde administration on non-selected BMAC via coronary sinus
Placebo Comparator: Control; standard treatment o heart failure	Drug: BMAC; retrograde administration on non-selected BMAC via coronary sinus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular end-systolic diameter (LVESd)	Left ventricular end-systolic diameter	12 month
Left ventricular end-systolic volume (LVESV)	Left ventricular end-systolic volume	12 month
Left ventricular end-diastolic diameter (LVEDd)	Left ventricular end-diastolic diameter	12 month
Left ventricular end-diastolic volume (LVEDV)	Left ventricular end-diastolic volume	12 month
ejection fraction of left ventricle (EF LV)	ejection fraction of left ventricle	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
corridor walk test	walk distance in 6 min corridor walk test	12 month
QoL	Quality of patients´ life using the Minnesota questionnaire	12 month

Collaborators and Investigators

• Sponsor: University Hospital Ostrava
• Investigators: Principal Investigator: Leoš Pleva, MD,PhD, University Hospital Ostrava

Publications and helpful links

General Publications

• Pleva L, Kukla P, Vitkova K, Prochazka V. Rationale and design of a prospective, randomised study of retrograde application of bone marrow aspirate concentrate (BMAC) through coronary sinus in patients with congestive heart failure of ischemic etiology (the RETRO study). BMC Cardiovasc Disord. 2019 Jan 31;19(1):32. doi: 10.1186/s12872-019-1011-9.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: December 10, 2017
• First Submitted That Met QC Criteria: December 10, 2017
• First Posted (Actual): December 14, 2017

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: FNO-Retro

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There exists no plan to make individual participant data available to other researchers. The data may be provided upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No