J Card Fail. 2023 Oct 21:S1071-9164(23)00352-4. doi: 10.1016/j.cardfail.2023.08.025. Online ahead of print.
ABSTRACT
BACKGROUND: Non-intravenous inotropic delivery options are needed for patients with inotropic dependent heart failure (HF) to reduce the costs, infection, and thrombotic risks associated with chronic central venous catheters and home infusion services.
METHODS: We developed a novel, concentrated formulation of nebulized milrinone for inhalation and evaluated the feasibility, safety, and pharmacokinetic profile in a prospective, single-arm, Phase I clinical trial. We enrolled 10 patients with Stage D HF requiring inotropic therapy during an acute HF hospital admission. Milrinone 60mg/4mL was inhaled via nebulization three times daily for 48 hours. The co-primary outcomes were adverse events and pharmacokinetic profile of inhaled milrinone. Acute changes in hemodynamic parameters were secondary outcomes.
RESULTS: A concentrated nebulized milrinone formulation was well tolerated without hypotensive events, arrhythmias, or inhalation-related adverse events requiring discontinuation. Nebulized milrinone produced serum concentrations in the goal therapeutic range with a median plasma milrinone trough concentration of 39 (17 - 66) ng/ml and a median peak concentration of 207 (134 - 293) ng/ml. There were no serious adverse events. From baseline to 24-hours, mean pulmonary artery saturation increased (60±7% to 65±5%; p=0.001), and mean cardiac index increased (2.0±0.5 ml/min/1.73m2 to 2.5±0.1 ml/min/1.73m2; p=0.001) with nebulized milrinone.
CONCLUSIONS: In a proof-of-concept study, a concentrated, nebulized milrinone formulation for inhalation was safe and produced therapeutic serum milrinone concentrations. Nebulized milrinone was associated with improved hemodynamic parameters of cardiac output in an advanced HF population. These promising results require further investigation in a longer-term trial in patients with inotrope-dependent advanced HF.
PMID:37871843 | DOI:10.1016/j.cardfail.2023.08.025