Phase 2
N=27
The Effects of Intravenous Heme Arginate on Heme Oxygenase-1 Expression (HO-1) and Oxidative Stress in the Human Heart
Myocardial Ischemia
Bottom Line
View on ClinicalTrials.gov: NCT02314780 ↗Enrolled (actual)
27
Serious AEs
11.1%
Results posted
Feb 2021
Primary outcome: Primary: Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue) — 392.7; 229.8; 10.8 arbitrary units — p==0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Heme arginate 3mg/kg (Drug); Heme arginate 1mg/kg (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Martin Andreas, M.D.
- Primary completion
- Jun 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue) |
392.7; 229.8; 10.8 | =0.001 sig |
| PRIMARY Myocardial HO-1 mRNA Levels (Ventricular Tissue Before Aortic Cross-clamping) |
203.6; 88.6; 7.9 | =0.002 sig |
| PRIMARY Myocardial HO-1 mRNA Levels (Ventricular Tissue After Aortic Cross-clamping) |
219.4; 108.1; 8.3 | =0.002 sig |
| PRIMARY Myocardial HO-1 Protein Concentrations (Atrial Tissue) |
29022; 28585; 8401 | <0.001 sig |
| PRIMARY Myocardial HO-1 Protein Concentrations (Ventricular Tissue Before Aortic Cross-clamping) |
13752; 10534; 6842 | =0.138 |
| PRIMARY Myocardial HO-1 Protein Concentrations (Ventricular Tissue After Aortic Cross-clamping) |
17062; 11277; 12037 | =0.696 |
Summary
Ischemia reperfusion injury may be attenuated by HO-1 induction. Our previous data confirmed strong HO-1 induction in peripheral blood cells following heme arginate infusion in healthy humans. Furthermore, we could demonstrate the amelioration of experimental ischemia reperfusion injury in the calf musculature by heme arginate in healthy subjects as measured by functional MRI.
Therefore, we propose that HO-1 induction in the human heart may be a suitable target to mitigate cardiac ischemia-reperfusion injury.
The HO-1 induction will be assessed in a clinical trial by myocardial biopsy prior to and after aortic cross-clamping in subjects with or without preceding heme arginate treatment in two different dosages. The HO-1 expression will also be measured in the clinical trials in peripheral blood mononuclear cells. As additional outcome, levels of myoglobin, creatine-kinase and troponin T and reactive oxygen species will be measured in plasma according to standard laboratory procedures.
Eligibility Criteria
Inclusion criteria
- Signed informed consent
- Men and women aged between 40 and 85 years (inclusive)
- Body mass index 45 mmHg
- Acute or recent (<7 days) myocardial infarction
- Child bearing potential
Data sourced from ClinicalTrials.gov (NCT02314780). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.