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

NCT ID: NCT02314780

Last Updated: 2021-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-29
• Study Completion Date: 2017-06-13

Brief 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.

Conditions

Myocardial Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Heme arginate (high dose)

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.

Group Type: EXPERIMENTAL

Heme arginate 3mg/kg

Intervention Type: DRUG

Heme arginate (low dose)

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.

Group Type: EXPERIMENTAL

Heme arginate 1mg/kg

Intervention Type: DRUG

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Heme arginate 3mg/kg

Intervention Type: DRUG

Heme arginate 1mg/kg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Normosang; Normosang; 0.9% sodium chloride solution

Eligibility 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

• 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Bank of Austria

OTHER_GOV

Sponsor Role: collaborator

Orphan Medical

INDUSTRY

Sponsor Role: collaborator

Martin Andreas, M.D.

OTHER

Sponsor Role: lead

Responsible Party

Martin Andreas, M.D.

M.D., PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alfred Kocher, M.D.

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, , Austria

Countries

Austria

References

Andreas M, Oeser C, Kainz FM, Shabanian S, Aref T, Bilban M, Messner B, Heidtmann J, Laufer G, Kocher A, Wolzt M. Intravenous Heme Arginate Induces HO-1 (Heme Oxygenase-1) in the Human Heart. Arterioscler Thromb Vasc Biol. 2018 Nov;38(11):2755-2762. doi: 10.1161/ATVBAHA.118.311832.

Reference Type: DERIVED

PMID: 30354231 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2013-000887-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HO-1 in the Heart

Identifier Type: -

Identifier Source: org_study_id