Low-dose dobutamine in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (the DOBERMANN-D trial): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

Abstract

Background: Cardiogenic shock (CS) occurs in 5-10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development.

Methods: This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h). The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24-48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed.

Discussion: Early inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up.

Trial registration: The Regional Ethics Committee : H-21045751. EudraCT: 2021-002028-19.

Clinicaltrials: gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277-8523.

Keywords: Acute myocardial infarction; Cardiogenic shock; Dobutamine; Hemodynamic; Inotropy; Neurohormonal activation; ORBI risk score; Percutaneous coronary intervention; Transthoracic echocardiography.

Fig. 1

Flowchart of the DOBERMANN-D trial—from screening to follow-up. Details concerning the tocilizumab/placebo intervention group are published separately (DOBERMANN-T). Abbreviations: RCT, randomized controlled trial; AMI, acute myocardial infarction; PCI, percutaneous coronary intervention; ORBI, Observatoire Régional Breton sur l’Infarctus; MRI, magnetic resonance imaging; proBNP, pro-B-type natriuretic peptide; H, hour; M, month

Fig. 2

Study procedure, interventions, and endpoints. Abbreviations: CS, Cardiogenic shock, ORBI, Observatoire Régional Breton sur l’Infarctus; TIMI, thrombolysis in myocardial infarction; MRI, magnetic resonance imaging; proBNP, pro-B-type natriuretic peptide