Mangafodipir as an Adjunct to Percutaneous Coronary Intervention (MANAMI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00966563
Recruitment Status : Completed
First Posted : August 27, 2009
Last Update Posted : July 16, 2013
Information provided by (Responsible Party):
PledPharma AB

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).

Condition or disease Intervention/treatment Phase
Myocardial Infarction Drug: Mangafodipir Drug: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Mangafodipir as an Adjunct to Percutaneous Coronary Intervention in Acute Myocardial Infarction (MANAMI)
Study Start Date : December 2009
Actual Primary Completion Date : May 2013
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Active Comparator: Mangafodipir treatment
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.
Drug: Mangafodipir
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
Other Name: Teslascan

Placebo Comparator: NaCl 0.9% Drug: Placebo

Primary Outcome Measures :
  1. Reduction of myocardial infarct size assessed by biomarker release to plasma [ Time Frame: Before and at 2 days after PCI ]

Secondary Outcome Measures :
  1. 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. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males 40-80 and females 50-80 years with first severe coronary attack
  2. Chest pain up to 6 hours.
  3. T segment elevation (≥ 0.2 mV in two neighbouring anterior and inferior wall leads.
  4. Decided for treatment by primary PCI.
  5. TIMI grade 0 flow in the occluded LAD or RCA artery
  6. Written informed consent.

Exclusion Criteria:

  1. Previous coronary artery bypass operation.
  2. Previous AMI.
  3. Chest pain more than 6 hours.
  4. Angina within 48 hours before admission.
  5. Cardiac arrest and cardiogenic shock.
  6. Occlusion of the left main stem, circumflex and right coronary arteries at angiography.
  7. Known hypersensitivity to mangafodipir (as contrast agent for MRI).
  8. Received mangafodipir ≤ 5 weeks before admission
  9. History of prior serious allergic or pseudo-allergic reaction
  10. Severely reduced liver or renal function
  11. Any other serious illness or medical condition
  12. Fertile females
  13. Phaeochromocytoma

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00966563

Department of Internal Medicine, County Hospital Ryhov
Jönköping, Sweden, 551 85
Sponsors and Collaborators
PledPharma AB
Principal Investigator: Jan-Erik Karlsson, MD, PhD Department of Internal Medicine, County Hospital Ryhov, SE-551 85 Jönköping, Sweden

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.

Responsible Party: PledPharma AB Identifier: NCT00966563     History of Changes
Other Study ID Numbers: MANAMI PP01-09
First Posted: August 27, 2009    Key Record Dates
Last Update Posted: July 16, 2013
Last Verified: July 2013

Keywords provided by PledPharma AB:
Primary Percutaneous Coronary Intervention
Myocardial infarction
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Myocardial Infarction
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Edetic Acid
Pyridoxal Phosphate
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs