"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

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

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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.

Original languageEnglish
Article number744
Number of pages10
JournalTrials
Volume21
Issue number1
DOIs
Publication statusPublished - 26 Aug 2020

Bibliographical note

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Keywords

  • Dutogliptin
  • Filgrastim
  • Myocardial infarction
  • Randomized controlled trial
  • SDF-1α

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