Mangafodipir as an Adjunct to Percutaneous Coronary Intervention (MANAMI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PledPharma AB
ClinicalTrials.gov Identifier:
NCT00966563
First received: August 26, 2009
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Myocardial Infarction
Drug: Mangafodipir
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Mangafodipir as an Adjunct to Percutaneous Coronary Intervention in Acute Myocardial Infarction (MANAMI)

Resource links provided by NLM:


Further study details as provided by PledPharma AB:

Primary Outcome Measures:
  • Reduction of myocardial infarct size assessed by biomarker release to plasma [ Time Frame: Before and at 2 days after PCI ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: December 2009
Study Completion Date: July 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00966563

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

No publications provided

Responsible Party: PledPharma AB
ClinicalTrials.gov Identifier: NCT00966563     History of Changes
Other Study ID Numbers: MANAMI PP01-09
Study First Received: August 26, 2009
Last Updated: July 15, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by PledPharma AB:
Mangafodipir
Primary Percutaneous Coronary Intervention
Myocardial infarction
Troponin
CK-MB
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Edetic Acid
Pyridoxal Phosphate
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014