Mangafodipir as an Adjunct to Percutaneous Coronary Intervention (MANAMI)
Primary Purpose
Myocardial Infarction
Status
Completed
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
Mangafodipir
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Infarction focused on measuring Mangafodipir, Primary Percutaneous Coronary Intervention, Myocardial infarction, Troponin, CK-MB, Magnetic Resonance Imaging
Eligibility Criteria
Inclusion Criteria:
- Males 40-80 and females 50-80 years with first severe coronary attack
- Chest pain up to 6 hours.
- T segment elevation (≥ 0.2 mV in two neighbouring anterior and inferior wall leads.
- Decided for treatment by primary PCI.
- TIMI grade 0 flow in the occluded LAD or RCA artery
- Written informed consent.
Exclusion Criteria:
- Previous coronary artery bypass operation.
- Previous AMI.
- Chest pain more than 6 hours.
- Angina within 48 hours before admission.
- Cardiac arrest and cardiogenic shock.
- Occlusion of the left main stem, circumflex and right coronary arteries at angiography.
- Known hypersensitivity to mangafodipir (as contrast agent for MRI).
- Received mangafodipir ≤ 5 weeks before admission
- History of prior serious allergic or pseudo-allergic reaction
- Severely reduced liver or renal function
- Any other serious illness or medical condition
- Fertile females
- Phaeochromocytoma
Sites / Locations
- Department of Internal Medicine, County Hospital Ryhov
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Mangafodipir treatment
NaCl 0.9%
Arm Description
Treatment will be undertaken with a ready-to use investigative drug formulation identical to what is in diagnostic use as a contrast medium for MRI. Formulation content: MnDPDP 10 mmol/ml.
Outcomes
Primary Outcome Measures
Reduction of myocardial infarct size assessed by biomarker release to plasma
Secondary Outcome Measures
Reduction of myocardial infarct size assessed by biomarker release to plasma and by magnetic resonance imaging (MRI) of the heart.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00966563
Brief Title
Mangafodipir as an Adjunct to Percutaneous Coronary Intervention
Acronym
MANAMI
Official Title
Mangafodipir as an Adjunct to Percutaneous Coronary Intervention in Acute Myocardial Infarction (MANAMI)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Egetis Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The present feasibility study is designed to find out whether pre-treatment with the compound mangafodipir (PP-099) provides an additional reduction in myocardial infarct size in patients treated with primary percutaneous coronary intervention (PCI) during acute myocardial infarction (AMI).
Detailed Description
Mangafodipir, manganese (Mn) dipyridoxyl diphosphate (MnDPDP) and its lipophile metabolite Mn dipyridoxyl diethylene diamide (MnPLED), are catalytic antioxidants and iron chelators. In preclinical studies these agents reduce oxidative stress induced injuries related to chemotherapy of cancer and to reperfusion/reoxygenation of ischemic/hypoxic myocardium. Accordingly, in an in vivo pig model of AMI metabolite MnPLED applied at end of ischemia and during reperfusion reduced myocardial infarct size by 55 %. Mangafodipir most likely activates salvage pathways and prevents lethal reperfusion injuries.
Other advantages are that mangafodipir is already approved as a contrast agent for MRI of liver, and that the experience for more than a decade reveals a high safety with minor and tolerable side-effects.
The present study will include 20 patients treated for their first documented AMI. They will after admission to hospital undergo primary PCI. Reopening of an occluded coronary artery will be preceded by iv. infusion of mangafodipir or placebo in two groups , each consisting of 10 patients. The primary endpoint will be release to plasma of commonly accepted biomarkers of myocardial injury (Troponin T and CK-MB) measured at admission and 6 hours after PCI. The secondary endpoints include the accumulated release of plasma biomarkers over 48 hours and direct measurement of the final myocardial infarct size at 6-10 weeks after PCI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
Keywords
Mangafodipir, Primary Percutaneous Coronary Intervention, Myocardial infarction, Troponin, CK-MB, Magnetic Resonance Imaging
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mangafodipir treatment
Arm Type
Active Comparator
Arm Description
Treatment will be undertaken with a ready-to use investigative drug formulation identical to what is in diagnostic use as a contrast medium for MRI. Formulation content: MnDPDP 10 mmol/ml.
Arm Title
NaCl 0.9%
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Mangafodipir
Other Intervention Name(s)
Teslascan
Intervention Description
Administered dose: 2 µmol/kg b.w. Administration form: Ready-to-use formulation (solution). Mangafodipir or placebo (0.2 ml/kg b.w.) will be administered as an intravenous (iv.) infusion over 2-5 min prior to reopening of occluded coronary artery during PCI
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Reduction of myocardial infarct size assessed by biomarker release to plasma
Time Frame
Before and at 2 days after PCI
Secondary Outcome Measure Information:
Title
Reduction of myocardial infarct size assessed by biomarker release to plasma and by magnetic resonance imaging (MRI) of the heart.
Time Frame
Accumulated biomarker release over 48 hours after PCI; MRI at 6-10 weeks after PCI.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males 40-80 and females 50-80 years with first severe coronary attack
Chest pain up to 6 hours.
T segment elevation (≥ 0.2 mV in two neighbouring anterior and inferior wall leads.
Decided for treatment by primary PCI.
TIMI grade 0 flow in the occluded LAD or RCA artery
Written informed consent.
Exclusion Criteria:
Previous coronary artery bypass operation.
Previous AMI.
Chest pain more than 6 hours.
Angina within 48 hours before admission.
Cardiac arrest and cardiogenic shock.
Occlusion of the left main stem, circumflex and right coronary arteries at angiography.
Known hypersensitivity to mangafodipir (as contrast agent for MRI).
Received mangafodipir ≤ 5 weeks before admission
History of prior serious allergic or pseudo-allergic reaction
Severely reduced liver or renal function
Any other serious illness or medical condition
Fertile females
Phaeochromocytoma
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan-Erik Karlsson, MD, PhD
Organizational Affiliation
Department of Internal Medicine, County Hospital Ryhov, SE-551 85 Jönköping, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Internal Medicine, County Hospital Ryhov
City
Jönköping
ZIP/Postal Code
551 85
Country
Sweden
12. IPD Sharing Statement
Citations:
Citation
1. Piot C, Croisille P, Staat P, Thibault H, Rioufol G et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. New Engl J Med 2008; 359: 473-481. 2. Yellon DM, Hausenloy DJ. Mechanisms of disease: Myocardial reperfusion injury. New Engl J Med 2007; 357: 1121-1135. 3. Karlsson JOG, Brurok H, Eriksen M, Towart R, Toft KG, Moen O, Engebretsen B, Jynge P and Refsum H. Cardioprotective effects of the MR contrast agent MnDPDP and its metabolite MnPLED upon reperfusion of the ischemic porcine myocardium. Acta Radiologica 2001;42:540-547. 4. Brurok H, Ardenkjær-Larsen JH, Hansson G, Skarra S, Berg K, Karlsson JOG, Jynge P. Manganese dipyridoxyl diphosphate: MRI contrast agent with antioxidative and cardioprotective properties. Biochem Biophys Res Commun 1999;254:768-772. 5. Karlsson JOG, Brurok H, Towart R, Jynge P. Letter to the Editor. The magnetic resonance imaging contrast agent mangafodipir exerts antitumor activity via a previously described superoxide mimetic activity. Cancer Res 2006;66:598. 6. MANFOL. Mangafodipir as an adjunct to FOLFOX6 chemotherapy in colon cancer stage Duke's C. Study NCT00671996. 2008. 7. Skjold A, Amundsen BH, Wiseth R, Støylen A, Haraldseth O, Larsson HB, Jynge P. Manganese dipyridoxyl-diphosphate (MnDPDP) as a viability marker in patients with myocardial infarction. J Magn Reson Imaging 2007; 26: 720-727. 8. Jynge P, Brurok H, Asplund A, Towart R, Refsum H, Karlsson JOG. Cardiovascular safety of MnDPDP and MnCl2. Acta Radiol 1997;38:740-749. 9. Karlsson JOG, Mortensen E, Pedersen HK, Sager G, Refsum H. Cardiovasular effects of MnDPDP and MnCl2 in dogs with acute ischemic heart failure. Acta Radiol 1997;38:750-758.
Results Reference
background
Learn more about this trial
Mangafodipir as an Adjunct to Percutaneous Coronary Intervention
We'll reach out to this number within 24 hrs