Does Heme Oxygenase-1 Induction Ameliorate Cardiac Injury After Myocardial Infarction?
Status:
Completed
Trial end date:
2010-02-01
Target enrollment:
Participant gender:
Summary
Rationale: A safety and dose defining study in which the investigators hypothesize that in
patients with acute coronary syndrome without ST-elevation (NSTEMI) treatment with heme
arginate results in better clinical outcome by inducing the heme oxygenase-1 (HO-1) pathway.
Objective: 1) Is induction of HO-1 and its degradation products, especially bilirubin, safe
in patients with an acute coronary syndrome without ST-elevation; 2) What is the optimal
effective dose to administer in patients with NSTEMI; 3) Are HO-1 and its degradation
products endogenously activated in patients with acute coronary syndrome; 4) Does treatment
with heme arginate result in a less cardiac damage; 5) Which other cardioprotecting pathways
are activated by administration of heme arginate?
Study population: Male and female patients with confirmed acute coronary syndrome without
ST-elevation, between 18 - 80 yr old.
Intervention: 10 patients receive a single administration of heme arginate (3 mg/kg),
administered intravenously in 15 minutes directly after admission; 10 patients receive two
administrations of heme arginate (3 mg/kg) on day 0 and 1; 10 patients receive three
administrations of heme arginate (3 mg/kg) on day 0, 1 and 2 after admission, administered
intravenously in 15 minutes. To determine endogenous levels of HO-1 and time course of HO-1
activation after NSTEMI, blood is drawn and the same assays are performed in 15 patients with
NSTEMI. As controls for the blood tests, blood is drawn and the same assays are performed in
15 patients with non-typical angina pectoris in whom no cardiac disease could be detected
from the investigators out-patient clinic.
Main study parameters/endpoints: The primary endpoint is the incidence rate of adverse events
between the three treated groups. This includes hemodynamic monitoring, rhythm monitoring and
biochemical and hematological difference between the three treated groups. Secondary
endpoints are the differences from baseline between heme arginate treated groups in activity
of the HO-1 pathway, including, but not limited to, HO-1 activity, free heme, bilirubin
(direct and indirect) levels, serum ferritin, and carbon monoxide (CO). Furthermore,
differences between heme arginate treated groups on NTproBNP, CK-MB and Troponin T and
difference between heme arginate treated subjects in LVEF measured by echocardiography, 3 and
7 days and 6 months after NSTEMI.