Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients (MIRON-DFP)

The objective of this randomized, controlled pilot study is to determine the efficacy of Deferiprone to reduce the amount of free iron inside the hemorrhagic zone of myocardial infarction among hemorrhagic myocardial infarction patients.

Study Overview

• Status: Recruiting
• Conditions: Acute Myocardial Infarction Type 1
• Intervention / Treatment: Drug: Deferiprone Tablets; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 89
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Research Coordinator; Phone Number: (317) 274-0985; Email: csaha@iu.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • IU Methodist Hospital (IUHealth)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age 18-79 years
2. Index Anterior wall STEMI
3. Emergency coronary angiogram with primary PCI

Exclusion Criteria

1. Prior history of MI / PCI / coronary artery bypass graft (CABG) within previous 1 year
2. Patients with previous history of left ventricular ejection fraction (LVEF) < 40%
3. Use of investigational drugs or devices 30 days prior to randomization
4. Known allergy or contra-indication to gadolinium/contrast agents
5. eGFR < 30 ml/kg/min
6. Any contraindication against cardiac MRI (such as metal implants)
7. Women who are pregnant or breastfeeding. Women of reproductive potential must have a negative pregnancy test prior to randomization
8. Body weight > 140 kg (or 309 lbs.)
9. Absolute neutrophil count - ANC < 1.5 k/cumm
10. History of Chronic Liver Disease
11. Elevated hepatic enzymes (BOTH ALT and AST) > 2 times of upper normal limit
12. Patients with iron storage disease (hemochromatosis, thalassemia) or who are already treated with iron chelators
13. Any clinically significant abnormality identified prior to randomization that in the judgment of the Sponsor-Investigator or Delegate would preclude safe completion of the study or confound the anticipated benefit of deferiprone.
14. Life expectancy of less than 1 year due to non-cardiac pathology

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hemorrhagic Myocardial Infarction - Deferiprone; Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage	Drug: Deferiprone Tablets; Deferiprone tablets are the active medication for the active arm of the study groups. Randomization will be done by investigational drug services pharmacist and intervention will be double-blinded to investigators and patients.
Active Comparator: Non-hemorrhagic Myocardial Infarction - Deferiprone; Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage	Drug: Deferiprone Tablets; Deferiprone tablets are the active medication for the active arm of the study groups. Randomization will be done by investigational drug services pharmacist and intervention will be double-blinded to investigators and patients.
Placebo Comparator: Hemorrhagic Myocardial Infarction - Placebo; Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage	Drug: Placebo; Deferiprone placebo is the non-medicated formulation for a control arm of the study groups.
Placebo Comparator: Non-hemorrhagic Myocardial Infarction - Placebo; Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage	Drug: Placebo; Deferiprone placebo is the non-medicated formulation for a control arm of the study groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Efficacy	Percentage reduction of hemorrhagic zone iron content by cardiac magnetic resonance at 6 months relative to baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Effect: Clinical Outcomes of Acute Heart Failure	The proportion of subjects who experience an acute heart failure event	6 months
Treatment Effect: Clinical Outcomes of Non-Fatal Cardiovascular morbidity	The proportion of subjects who experience other non-fatal cardiovascular morbidity such as recurrent myocardial infarction, ventricular arrhythmia and CVA	6 months
Safety and Tolerability - Rate of Discontinuation	Rate of discontinuation of therapy due to side effects	6 months
Safety and Tolerability - Severe Side Effects	Rate of severe side effects requiring hospitalization, extension of length-of-stay.	6 months
Safety and Tolerability - Reversibility of Side Effects without Treatment	Percentage of Reversible of Side Effects without treatment	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Effect: Fat Infiltration	Percentage difference of fat infiltration within the hemorrhagic myocardial infarction arms at 6 months between deferiprone and placebo groups	6 months

Collaborators and Investigators

• Sponsor: Rohan Dharmakumar
• Collaborators: Minneapolis Heart Institute
• Investigators: Principal Investigator: Rohan Dharmakumar, PhD, Medical Imaging Research Institute, Indiana University School of Medicine; Principal Investigator: Keyur P Vora, MD FACP FACC, Medical Imaging Research Institute, Indiana University School of Medicine

Publications and helpful links

General Publications

• Kali A, Kumar A, Cokic I, Tang RL, Tsaftaris SA, Friedrich MG, Dharmakumar R. Chronic manifestation of postreperfusion intramyocardial hemorrhage as regional iron deposition: a cardiovascular magnetic resonance study with ex vivo validation. Circ Cardiovasc Imaging. 2013 Mar 1;6(2):218-28. doi: 10.1161/CIRCIMAGING.112.000133. Epub 2013 Feb 12.
• Kali A, Cokic I, Tang R, Dohnalkova A, Kovarik L, Yang HJ, Kumar A, Prato FS, Wood JC, Underhill D, Marban E, Dharmakumar R. Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse Remodeling. Circ Cardiovasc Imaging. 2016 Nov;9(11):e004996. doi: 10.1161/CIRCIMAGING.115.004996.
• Wang G, Yang HJ, Kali A, Cokic I, Tang R, Xie G, Yang Q, Francis J, Li S, Dharmakumar R. Influence of Myocardial Hemorrhage on Staging of Reperfused Myocardial Infarctions With T2 Cardiac Magnetic Resonance Imaging: Insights Into the Dependence on Infarction Type With Ex Vivo Validation. JACC Cardiovasc Imaging. 2019 Apr;12(4):693-703. doi: 10.1016/j.jcmg.2018.01.018. Epub 2018 Apr 18.
• Liu T, Howarth AG, Chen Y, Nair AR, Yang HJ, Ren D, Tang R, Sykes J, Kovacs MS, Dey D, Slomka P, Wood JC, Finney R, Zeng M, Prato FS, Francis J, Berman DS, Shah PK, Kumar A, Dharmakumar R. Intramyocardial Hemorrhage and the "Wave Front" of Reperfusion Injury Compromising Myocardial Salvage. J Am Coll Cardiol. 2022 Jan 4;79(1):35-48. doi: 10.1016/j.jacc.2021.10.034.
• Dharmakumar R. "Rusty Hearts": Is It Time to Rethink Iron Chelation Therapies in Post-Myocardial-Infarction Setting? Circ Cardiovasc Imaging. 2016 Oct;9(10):e005541. doi: 10.1161/CIRCIMAGING.116.005541. No abstract available.
• Dharmakumar R. Colors of Myocardial Infarction: Can They Predict the Future? Circ Cardiovasc Imaging. 2017 Dec;10(12):e007291. doi: 10.1161/CIRCIMAGING.117.007291. No abstract available.
• Dharmakumar R, Nair AR, Kumar A, Francis J. Myocardial Infarction and the Fine Balance of Iron. JACC Basic Transl Sci. 2021 Jul 26;6(7):581-583. doi: 10.1016/j.jacbts.2021.06.004. eCollection 2021 Jul.
• Guan X, Chen Y, Yang HJ, Zhang X, Ren D, Sykes J, Butler J, Han H, Zeng M, Prato FS, Dharmakumar R. Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2021 Jul 15;23(1):88. doi: 10.1186/s12968-021-00787-4.
• Kali A, Tang RL, Kumar A, Min JK, Dharmakumar R. Detection of acute reperfusion myocardial hemorrhage with cardiac MR imaging: T2 versus T2. Radiology. 2013 Nov;269(2):387-95. doi: 10.1148/radiology.13122397. Epub 2013 Jul 11.
• Cokic I, Kali A, Yang HJ, Yee R, Tang R, Tighiouart M, Wang X, Jackman WS, Chugh SS, White JA, Dharmakumar R. Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction: Early Evidence. Circ Cardiovasc Imaging. 2015 Aug;8(8):10.1161/CIRCIMAGING.115.003642 e003642. doi: 10.1161/CIRCIMAGING.115.003642.
• Cokic I, Kali A, Wang X, Yang HJ, Tang RL, Thajudeen A, Shehata M, Amorn AM, Liu E, Stewart B, Bennett N, Harlev D, Tsaftaris SA, Jackman WM, Chugh SS, Dharmakumar R. Iron deposition following chronic myocardial infarction as a substrate for cardiac electrical anomalies: initial findings in a canine model. PLoS One. 2013 Sep 16;8(9):e73193. doi: 10.1371/journal.pone.0073193. eCollection 2013.
• Nair AR, Johnson EA, Yang HJ, Cokic I, Francis J, Dharmakumar R. Reperfused hemorrhagic myocardial infarction in rats. PLoS One. 2020 Dec 2;15(12):e0243207. doi: 10.1371/journal.pone.0243207. eCollection 2020.
• Chen Y, Ren D, Guan X, Yang HJ, Liu T, Tang R, Ho H, Jin H, Zeng M, Dharmakumar R. Quantification of myocardial hemorrhage using T2* cardiovascular magnetic resonance at 1.5T with ex-vivo validation. J Cardiovasc Magn Reson. 2021 Sep 30;23(1):104. doi: 10.1186/s12968-021-00779-4.

Helpful Links

• CARDIO-THERANOSTICS is developing diagnostics and therapeutics for hemorrhagic myocardial infarction

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2022
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: October 7, 2022
• First Submitted That Met QC Criteria: October 27, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Acute Myocardial Infarction; Deferiprone; Intramyocardial Hemorrhage
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; Myocardial Infarction; Infarction; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridones; Deferiprone
• Other Study ID Numbers: 13487

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No