The Effects of Intravenous Heme Arginate on Heme Oxygenase-1 Expression (HO-1) and Oxidative Stress in the Human Heart

Martin Andreas, M.D.

Status and phase: Completed; Phase 2

Conditions: Myocardial Ischemia

Treatments: Drug: Heme arginate 3mg/kg; Drug: Placebo; Drug: Heme arginate 1mg/kg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02314780

HO-1 in the Heart

2013-000887-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 31 patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria:

• Signed informed consent
• Men and women aged between 40 and 85 years (inclusive)
• Body mass index < 35 kg/m2
• Ability to communicate well with the investigator in the local language and to understand and comply with the requirements of the study

Exclusion criteria (any of the following):

• Known hypersensitivity to the study drug or any excipients of the drug formulation
• Treatment with another investigational drug within 3 weeks prior to screening
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug
• Severe renal failure (glomerula filtration rate < 30 ml/min)
• Moderately or severe impaired left ventricular function (ejection fraction < 40%)
• Moderately or severe impaired right ventricular function
• Systolic pulmonary pressure > 45 mmHg
• Acute or recent (<7 days) myocardial infarction
• Child bearing potential

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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31 participants in 3 patient groups, including a placebo group

Heme arginate (high dose)

Experimental group

Description:

24 hours prior to the planned surgical aortic valve replacement, heme arginate at a dose of 3 mg/kg diluted to 110ml with 0.9% sodium chloride was administered at a single intravenous infusion using an infusion pump.

Treatment:

Drug: Heme arginate 3mg/kg

Heme arginate (low dose)

Experimental group

Description:

24 hours prior to the planned surgical aortic valve replacement, heme arginate at a dose of 1 mg/kg diluted to 110ml with 0.9% sodium chloride was administered at a single intravenous infusion using an infusion pump.

Treatment:

Drug: Heme arginate 1mg/kg

Placebo

Placebo Comparator group

Description:

24 hours prior to the planned surgical aortic valve replacement, subjects received a single intravenous infusion of an equivalent volume of 0.9% sodium chloride solution.

Treatment:

Drug: Placebo