Myocardial IschemiaPhase 2NCT02314780
The Effects of Intravenous Heme Arginate on Heme Oxygenase-1 Expression (HO-1) and Oxidative Stress in the Human Heart
A Phase 2 study testing Heme arginate 3mg/kg and Heme arginate 1mg/kg in people with Myocardial Ischemia, run by Martin Andreas, M.D. at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Myocardial Ischemia
- What is being tested?
- Heme arginate 3mg/kg and Heme arginate 1mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteAustria
- Study dates
- 29 Mar 2015to 13 Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Systolic pulmonary pressure > 45 mmHg
- Acute or recent (<7 days) myocardial infarction
- Child bearing potential
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Trial: The Effects of Intravenous Heme Arginate on HO-1 Expression and Oxidative Stress in the Human Heart
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
- Being tested
- Heme arginate 3mg/kg, Heme arginate 1mg/kg, Placebo
- Keywords
- carboxyhemoglobin, neutrophil, reactive oxygen species, reperfusion injury
- Medical subject headings
- Myocardial Ischemia, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heme arginate 3mg/kgDrug
Also called Normosang
Heme arginate 1mg/kgDrug
Also called Normosang
PlaceboDrug
Also called 0.9% sodium chloride solution
| Study group | Role | What they receive |
|---|---|---|
| Heme arginate (high dose) | Experimental | 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. Receives: Drug: Heme arginate 3mg/kg |
| Heme arginate (low dose) | Experimental | 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. Receives: Drug: Heme arginate 1mg/kg |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue)
The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.
Measured: intraoperative
Myocardial HO-1 mRNA Levels (Ventricular Tissue Before Aortic Cross-clamping)
A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen in the operating theater after sampling.
Measured: intraoperative
Myocardial HO-1 mRNA Levels (Ventricular Tissue After Aortic Cross-clamping)
A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.
Measured: intraoperative
Myocardial HO-1 Protein Concentrations (Atrial Tissue)
The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass.The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Measured: intraoperative
Myocardial HO-1 Protein Concentrations (Ventricular Tissue Before Aortic Cross-clamping)
A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Measured: intraoperative
Myocardial HO-1 Protein Concentrations (Ventricular Tissue After Aortic Cross-clamping)
A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Measured: intraoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2014 (estimated)
- Study start29 Mar 2015
- Primary completion13 Jun 2017
- Study completion13 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Martin Andreas, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- National Bank of Austria, Orphan Medical
- Responsible party
- Sponsor-investigator, Martin Andreas, M.D., Medical University of Vienna
- Investigators
- Alfred Kocher, M.D., Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02314780
- Sponsor's protocol ID
- HO-1 in the Heart
- Other IDs
- 2013-000887-27
- Status last verified
- Jan 2021
- First submitted
- 8 Dec 2014
- Last updated
- 15 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30354231
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Trial: The Effects of Intravenous Heme Arginate on HO-1 Expression and Oxidative Stress in the Human Heart
- ClinicalTrials.gov ID
- NCT02314780
- Acronym / sponsor ID
- HO-1 in the Heart
- Conditions
- Myocardial Ischemia
- Keywords
- carboxyhemoglobin, neutrophil, reactive oxygen species, reperfusion injury
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Martin Andreas, M.D.University, hospital or other
- Collaborators
- National Bank of Austria, Orphan Medical
- Study start
- 29 Mar 2015 (actual)
- Primary completion
- 13 Jun 2017 (actual)
- Study completion
- 13 Jun 2017 (actual)
- First posted
- 11 Dec 2014 (estimated)
- Results
- Posted 15 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Heme arginate (high dose) | Experimental | Drug: Heme arginate 3mg/kg24 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. |
| Heme arginate (low dose) | Experimental | Drug: Heme arginate 1mg/kg24 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. |
| Placebo | Placebo comparator | Drug: Placebo24 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. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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%)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Heme arginate 3mg/kgAlso: Normosang | Drug | Heme arginate (high dose) |
| Heme arginate 1mg/kgAlso: Normosang | Drug | Heme arginate (low dose) |
| PlaceboAlso: 0.9% sodium chloride solution | Drug | Placebo |
Primary outcome
Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue)
Time frame: intraoperative
The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.
Myocardial HO-1 mRNA Levels (Ventricular Tissue Before Aortic Cross-clamping)
Time frame: intraoperative
A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen in the operating theater after sampling.
Myocardial HO-1 mRNA Levels (Ventricular Tissue After Aortic Cross-clamping)
Time frame: intraoperative
A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.
Myocardial HO-1 Protein Concentrations (Atrial Tissue)
Time frame: intraoperative
The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass.The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Myocardial HO-1 Protein Concentrations (Ventricular Tissue Before Aortic Cross-clamping)
Time frame: intraoperative
A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Myocardial HO-1 Protein Concentrations (Ventricular Tissue After Aortic Cross-clamping)
Time frame: intraoperative
A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30354231Andreas 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfred Kocher, M.D. principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Heme arginate 3mg/kg and Heme arginate 1mg/kg in people with Myocardial Ischemia, run by Martin Andreas, M.D. at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue) (time frame: intraoperative). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02314780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2021.