Bone Marrow Derived Adult Stem Cells for Chronic Heart Failure (REGEN-IHD)

Barts & The London NHS Trust

Status and phase: Completed; Phase 3; Phase 2

Conditions: Chronic Ischaemic Heart Failure

Treatments: Procedure: Percutaneous intracoronary injection; Drug: Granulocyte-colony stimulating factor; Procedure: Percutaneous intramyocardial injection

Study type: Interventional

Funder types: Other

Identifiers

NCT00747708

04/Q0603/13

2005-002706-27 (EudraCT)

Details and patient eligibility

About

The purpose of this study is to determine whether adult bone marrow derived stem/progenitor cells improve cardiac function and symptoms in patients with heart failure and to establish the optimal method of delivery of these cells.

Study hypotheses:

• Administration of G-CSF to patients with heart failure secondary to ischaemic heart disease will lead to an increase in circulating progenitor cells as measured by peripheral CD34+ positive cell counts
• Cardiac function and symptoms will improve in patients in whom the peripheral CD34+ counts increase in response to G-CSF administration
• Direct coronary injection of autologous bone marrow derived stem cells will confer an additional improvement in cardiac function and symptoms above that derived from G-CSF infusion alone
• Direct intramyocardial injection of autologous bone marrow derived stem cells will lead to an improvement in cardiac function and symptoms above that derived from G-CSF infusion alone

Full description

The study involves three arms that compare the method of autologous bone marrow cel administration in patients with chronic heart failure. Each arm has a comparative group that contains either saline injection (peripheral arm that injects GCSF alone) or serum (the two interventional arms-intracoronary and intramyocardial injection).

The protocol (on the advice of the ethics committee) is divided into a 58 patients pilot study followed by recruitment into the intramyocardial arm (30 patients randomised 1:1 cells in serum vs serum alone) and then recruitment into the intracoronary and peripheral arms (30 patients randomised 1:1 cells in serum vs serum alone in each arm).

The study has been powered around the use of advanced imaging to measure within group changes in ejection fraction at 12 months as the primary end point.

Enrollment: 148 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Symptomatic patients with a diagnosis of heart failure secondary to ischaemic heart disease who are on optimal heart failure treatment and no further treatment options available
• Patient has been considered for an implantable defibrillator in keeping with NICE guidelines

Exclusion criteria

• Recent acute coronary syndrome as judged by a rise of Troponin above normal values in the last 6 months
• The presence of cardiogenic shock
• The presence of acute left and/or right-sided pump failure as judged by the presence of pulmonary oedema and/or new peripheral oedema
• Known severe pre-existent left ventricular dysfunction (ejection fraction < 10% prior to randomisation)
• Congenital cardiac disease
• Cardiomyopathy secondary to a reversible cause e.g. thyroid disease, alcohol abuse, hypophosphataemia, hypocalcaemia, cocaine abuse, selenium toxicity & chronic uncontrolled tachycardia
• Cardiomyopathy in association with a neuromuscular disorder e.g. Duchenne's progressive muscular dystrophy
• Contra-indication for bone marrow aspiration
• Known active infection
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) syphilis or HTLV
• Lifestyle with high risk for infection with HIV, HBV or HCV syphilis or HTLV
• Serum creatinine >200 umol/L
• Chronic inflammatory disease
• Serious known concomitant disease with a life expectancy of less than one year
• Follow-up impossible (no fixed abode, etc)
• Previous participation in this study
• Female subjects of childbearing potential
• Atrial fibrillation
• Patients who have responded to the implantation of a biventricular pacemaker
• Weight >140kg

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

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148 participants in 3 patient groups

Peripheral

Experimental group

Description:

Patients are randomised in a 1:1 ratio to receive granulocyte-colony stimulating factor (G-CSF) or placebo injection

Treatment:

Drug: Granulocyte-colony stimulating factor

Percutaneous intracoronary injection

Experimental group

Description:

All patients will receive granulocyte-colony stimulating factor injections followed by a bone marrow aspiration. Patients will be randomised in a 1:1 ratio to receive intracoronary injections of bone marrow derived stem/progenitor cells or placebo infusion through a percutaneous route

Treatment:

Procedure: Percutaneous intracoronary injection

Drug: Granulocyte-colony stimulating factor

Percutaneous intramyocardial injection

Experimental group

Description:

All patients will receive granulocyte-colony stimulating factor injections followed by a bone marrow aspiration. Patients will be randomised in a 1:1 ratio to receive intramyocardial injections of bone marrow derived stem/progenitor cells or placebo infusion through a percutaneous route

Treatment:

Procedure: Percutaneous intramyocardial injection

Drug: Granulocyte-colony stimulating factor