Abstract
BackgroundMyocardial injury of ST-segment elevation myocardial infarction (STEMI) initiates an intense inflammatory response that contributes to further damage and is a predictor of increased risk of death or heart failure (HF). Interleukin-1 (IL-1) is a key mediator of local and systemic inflammatory response to myocardial damage. We postulate that the use of the drug RPH-104, which selectively binds and inactivates both α and β isoforms of IL-1 will lead to a decrease in the severity of the inflammatory response which will be reflected by decrease in the concentration of hsCRP, as well as the rate of fatal outcomes, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP) and changes in structural and functional echocardiographic parameters.MethodsThis is a double blind, randomized, placebo-controlled study in which 102 patients with STEMI will receive a single administration of RPH-104 80 mg, RPH-104 160 mg or placebo (1:1:1). The primary endpoint will be hsCRP area under curve (AUC) from day 1 until day 14. Secondary endpoints will include hsCRP AUC from day 1 until day 28, rate of fatal outcomes, hospitalizations due to HF and other cardiac and non-cardiac reasons during 12-month follow-up period, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP, NT-pro-BNP), changes in structural and functional echocardiographic parameters during 12-month follow-up period compared to baseline. The study started in October 2020 and is anticipated to end in 2Q 2022.Trial registration: ClinicalTrials.gov, NCT04463251. Registered on July 9, 2020
Highlights
Myocardial injury of ST-segment elevation myocardial infarction (STEMI) initiates an intense inflammatory response that contributes to further damage and is a predictor of increased risk of death or heart failure (HF)
Studies have shown that an increased concentration of a highly sensitive C-reactive protein, which is a marker of the inflammatory response and a surrogate marker of IL-1 activity, in patients with acute coronary syndrome/ myocardial infarction is independently associated with a risk of adverse cardiovascular outcomes in subsequent events [6, 13, 19]
The secondary endpoints will include highly sensitive C-reactive protein (hsCRP) area under curve (AUC) from day 1 until Day 28, rate of fatal outcomes, hospitalizations, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP, NTpro-BNP) during 12-month follow-up period compared to baseline and changes in structural and functional echocardiographic parameters, including, but not limited to, left ventricular (LV) dimensions, LVMI, systolic and diastolic function after 12 months compared to baseline
Summary
Design Our trial is a multicenter, phase IIa, double-blind, randomized, placebo-controlled clinical study comparing single administration of RPH-104 80 mg, RPH-104 160 mg and placebo (1:1:1 randomization) in subjects with STEMI at the study sites in the Russian Federation and in the USA. The secondary endpoints will include hsCRP area under curve (AUC) from day 1 (baseline) until Day 28, rate of fatal outcomes (cardiac and non-cardiac), hospitalizations (due to HF and other cardiac reasons not associated with HF or due to non-cardiac reasons), frequency of new cases of HF (defined as hospitalization due to HF or necessity in a loop diuretic administration intravenously or oral dose doubling in the relevant clinical facilities), changes in levels of brain natriuretic peptide (BNP, NTpro-BNP) during 12-month follow-up period compared to baseline and changes in structural and functional echocardiographic parameters, including, but not limited to, left ventricular (LV) dimensions, LVMI, systolic and diastolic function after 12 months compared to baseline. Changes in BNP, NT-pro-BNP levels will be presented by descriptive statistics by the study visits and treatment groups.
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