Mangafodipir as an Adjunct to Percutaneous Coronary Intervention (MANAMI)

July 15, 2013 updated by: Egetis Therapeutics

Mangafodipir as an Adjunct to Percutaneous Coronary Intervention in Acute Myocardial Infarction (MANAMI)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Jönköping, Sweden, 551 85
        • Department of Internal Medicine, County Hospital Ryhov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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 Names:
  • Teslascan
Placebo Comparator: NaCl 0.9%
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reduction of myocardial infarct size assessed by biomarker release to plasma
Time Frame: Before and at 2 days after PCI
Before and at 2 days after PCI

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
Accumulated biomarker release over 48 hours after PCI; MRI at 6-10 weeks after PCI.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Egetis Therapeutics

Investigators

  • Principal Investigator: Jan-Erik Karlsson, MD, PhD, Department of Internal Medicine, County Hospital Ryhov, SE-551 85 Jönköping, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

August 26, 2009

First Submitted That Met QC Criteria

August 26, 2009

First Posted (Estimate)

August 27, 2009

Study Record Updates

Last Update Posted (Estimate)

July 16, 2013

Last Update Submitted That Met QC Criteria

July 15, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MANAMI PP01-09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myocardial Infarction

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe