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Trials
Published in: Trials 1/2020

Open Access 01-12-2020 | Filgrastim | Study protocol

“Protocol for a phase 2, randomized, double-blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-myocardial infarction”: study protocol for a randomized controlled trial

Authors: Dirk von Lewinski, Joseph B. Selvanayagam, Richard A. Schatz, Bernd Jilma, Jacek Kubica, Thomas J. Povsic, Darrell Nix, Stephan Henauer, Markus Wallner, on behalf of the REC-DUT-002 study group

Published in: Trials | Issue 1/2020

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Abstract

Background

Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Previous trials using bone marrow cells, selected stem cell populations, or cardiac stem cell progenitors require invasive procedures and had so far inconclusive results. A less invasive approach utilizes granulocyte-colony stimulating factor (G-CSF) to mobilize stem cells to circulating blood and induce neovascularization and differentiation into endothelial cells and cardiomyocytes. Stromal cell-derived factor 1 alpha (SDF-1α) is an important chemokine for initiating stem cell migration and homing to ischemic myocardium. SDF-1α concentrations can be increased by inhibition of CD26/DPP4. Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model.

Methods

We test the safety and tolerability and efficacy of dutogliptin in combination with filgrastim (G-CSF) in patients with STEMI (EF < 45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect > 3.8% improvement in left ventricular ejection fraction (LV-EF) compared to placebo. One hundred forty subjects will be randomized to filgrastim plus dutogliptin or matching placebos.

Discussion

The REC-DUT-002 trial is the first to evaluate dutogliptin in combination with G-CSF in patients with STEMI. Results will lay the foundation for an appropriately powered cardiovascular outcome trial to test the efficacy of this combined pharmacological strategy.

Trial registration

EudraCT no.​:​ 2018-000916-75. Registered on 7 June 2018. IND number: 123717
Appendix
Available only for authorised users
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Metadata
Title
“Protocol for a phase 2, randomized, double-blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-myocardial infarction”: study protocol for a randomized controlled trial
Authors
Dirk von Lewinski
Joseph B. Selvanayagam
Richard A. Schatz
Bernd Jilma
Jacek Kubica
Thomas J. Povsic
Darrell Nix
Stephan Henauer
Markus Wallner
on behalf of the REC-DUT-002 study group
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-020-04652-0

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