Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction-The REC-DUT-002 Trial.
Dirk von LewinskiMartin BenediktHannes AlberJan DebrauwerePieter C SmitsIstván ÉdesRóbert Gábor KissBéla MerkelyGergely Gyorgy NagyPawel PtaszynskiMaciej ZarebinskiJacek KubicaAndrzej KleinrokAndrew J S CoatsMarkus WallnerPublished in: Journal of clinical medicine (2022)
Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients ( n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.
Keyphrases
- left ventricular
- double blind
- ejection fraction
- acute myocardial infarction
- percutaneous coronary intervention
- heart failure
- st elevation myocardial infarction
- phase iii
- placebo controlled
- sars cov
- magnetic resonance imaging
- aortic stenosis
- study protocol
- phase ii
- stem cells
- coronary artery disease
- open label
- healthcare
- atrial fibrillation
- randomized controlled trial
- computed tomography
- st segment elevation myocardial infarction
- acute coronary syndrome
- coronary artery bypass grafting
- combination therapy
- risk assessment
- mitral valve
- antiplatelet therapy
- health information
- left atrial
- transcatheter aortic valve replacement
- chronic kidney disease
- replacement therapy
- wound healing
- contrast enhanced
- cerebrospinal fluid
- drug administration
- diffusion weighted imaging