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

Primary Purpose

Acute Myocardial Infarction Type 1

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Deferiprone Tablets
Placebo
Sponsored by
Rohan Dharmakumar
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myocardial Infarction Type 1 focused on measuring Acute Myocardial Infarction, Intramyocardial Hemorrhage, Deferiprone

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Index Anterior wall STEMI, based on American Heart Association guidelines diagnostic criteria: Symptoms of myocardial ischemia (such as chest pain, shortness of breath, jaw pain, arm pain, diaphoresis, or any anginal equivalent) and ECG: New or presumed new ST-segment elevation at the J point in two or more contiguous leads with the cut-off points ≥0.2 mV in leads V1, V2, V3, or V4 and ≥ 0.1 mV in other leads Elevated biomarkers (Troponin) Coronary angiogram with primary PCI to occur irrespective of the duration of the symptoms. Exclusion Criteria Prior history of MI / PCI / CABG Patients with history of LVEF < 40% Use of investigational drugs or devices 30 days prior to randomization Known allergy or contra-indication to gadolinium/contrast agents eGFR < 30 ml/kg/min Any contraindication against cardiac MRI (such as metal implants) Women who are pregnant or breastfeeding. Women of reproductive potential must have a negative pregnancy test prior to randomization Body weight > 140 kg (or 309 lbs.) Absolute neutrophil count of ANC < 1.0 x 109 /L Elevated hepatic enzymes (SGPT/ SGLT > 2 times of upper normal limit) Patients with iron storage disease (hemochromatosis, thalassemia) or who are already treated with iron chelators Any clinically significant abnormality identified prior to randomization that in the judgment of the Investigator or Sponsor would preclude safe completion of the study or confound the anticipated benefit of LIPOMED. Life expectancy of less than 1 year due to non-cardiac pathology

Sites / Locations

  • Krannert Cardiovascular Research CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Placebo Comparator

Arm Label

Hemorrhagic Myocardial Infarction - Deferiprone

Non-hemorrhagic Myocardial Infarction - Deferiprone

Hemorrhagic Myocardial Infarction - Placebo

Non-hemorrhagic Myocardial Infarction - Placebo

Arm Description

Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage

Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage

Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage

Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage

Outcomes

Primary Outcome Measures

Treatment Efficacy
Percentage reduction of hemorrhagic zone iron content by cardiac magnetic resonance at 6 months relative to baseline

Secondary Outcome Measures

Treatment Effect: Fat Infiltration
Percentage difference of fat infiltration within the hemorrhagic myocardial infarction arms at 6 months between deferiprone and placebo groups
Treatment Effect: Clinical Outcomes
The proportion of subjects who experience an acute heart failure event The proportion of subjects who experience other non-fatal cardiovascular morbidity such as recurrent myocardial infarction, ventricular arrhythmia and CVA
Safety and Tolerability
Incidence and severity of AEs and changes from baseline of all study parameters, including clinical laboratory values, vital signs and ECG. Severity of AEs will be assessed according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, v5.0). All subjects will be monitored for AEs until resolution

Full Information

First Posted
October 7, 2022
Last Updated
December 14, 2022
Sponsor
Rohan Dharmakumar
Collaborators
Cardio-theranostics LLC, Lipomed AG
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1. Study Identification

Unique Protocol Identification Number
NCT05604131
Brief Title
Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients
Acronym
MIRON-DFP
Official Title
Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 24, 2022 (Actual)
Primary Completion Date
November 23, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Rohan Dharmakumar
Collaborators
Cardio-theranostics LLC, Lipomed AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction Type 1
Keywords
Acute Myocardial Infarction, Intramyocardial Hemorrhage, Deferiprone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hemorrhagic Myocardial Infarction - Deferiprone
Arm Type
Active Comparator
Arm Description
Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage
Arm Title
Non-hemorrhagic Myocardial Infarction - Deferiprone
Arm Type
Active Comparator
Arm Description
Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage
Arm Title
Hemorrhagic Myocardial Infarction - Placebo
Arm Type
Placebo Comparator
Arm Description
Enrolled patients with CMR confirmed presence of intramyocardial hemorrhage
Arm Title
Non-hemorrhagic Myocardial Infarction - Placebo
Arm Type
Placebo Comparator
Arm Description
Enrolled patients with CMR confirmed absence of intramyocardial hemorrhage
Intervention Type
Drug
Intervention Name(s)
Deferiprone Tablets
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Deferiprone placebo is the non-medicated formulation for a control arm of the study groups.
Primary Outcome Measure Information:
Title
Treatment Efficacy
Description
Percentage reduction of hemorrhagic zone iron content by cardiac magnetic resonance at 6 months relative to baseline
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Treatment Effect: Fat Infiltration
Description
Percentage difference of fat infiltration within the hemorrhagic myocardial infarction arms at 6 months between deferiprone and placebo groups
Time Frame
6 months
Title
Treatment Effect: Clinical Outcomes
Description
The proportion of subjects who experience an acute heart failure event The proportion of subjects who experience other non-fatal cardiovascular morbidity such as recurrent myocardial infarction, ventricular arrhythmia and CVA
Time Frame
6 months
Title
Safety and Tolerability
Description
Incidence and severity of AEs and changes from baseline of all study parameters, including clinical laboratory values, vital signs and ECG. Severity of AEs will be assessed according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, v5.0). All subjects will be monitored for AEs until resolution
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Index Anterior wall STEMI, based on American Heart Association guidelines diagnostic criteria: Symptoms of myocardial ischemia (such as chest pain, shortness of breath, jaw pain, arm pain, diaphoresis, or any anginal equivalent) and ECG: New or presumed new ST-segment elevation at the J point in two or more contiguous leads with the cut-off points ≥0.2 mV in leads V1, V2, V3, or V4 and ≥ 0.1 mV in other leads Elevated biomarkers (Troponin) Coronary angiogram with primary PCI to occur irrespective of the duration of the symptoms. Exclusion Criteria Prior history of MI / PCI / CABG Patients with history of LVEF < 40% Use of investigational drugs or devices 30 days prior to randomization Known allergy or contra-indication to gadolinium/contrast agents eGFR < 30 ml/kg/min Any contraindication against cardiac MRI (such as metal implants) Women who are pregnant or breastfeeding. Women of reproductive potential must have a negative pregnancy test prior to randomization Body weight > 140 kg (or 309 lbs.) Absolute neutrophil count of ANC < 1.0 x 109 /L Elevated hepatic enzymes (SGPT/ SGLT > 2 times of upper normal limit) Patients with iron storage disease (hemochromatosis, thalassemia) or who are already treated with iron chelators Any clinically significant abnormality identified prior to randomization that in the judgment of the Investigator or Sponsor would preclude safe completion of the study or confound the anticipated benefit of LIPOMED. Life expectancy of less than 1 year due to non-cardiac pathology
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Keyur P Vora, MD FACC
Phone
3172740975
Email
kpvora@iu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rohan Dharmakumar, PhD
Organizational Affiliation
Krannert Cardiovascular Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Krannert Cardiovascular Research Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23403335
Citation
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.
Results Reference
background
PubMed Identifier
27903536
Citation
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.
Results Reference
background
PubMed Identifier
29680356
Citation
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.
Results Reference
background
PubMed Identifier
34991787
Citation
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.
Results Reference
background
PubMed Identifier
27894072
Citation
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.
Results Reference
background
PubMed Identifier
29242241
Citation
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.
Results Reference
background
PubMed Identifier
34368506
Citation
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.
Results Reference
background
PubMed Identifier
34261494
Citation
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.
Results Reference
background
PubMed Identifier
34587984
Citation
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. Erratum In: J Cardiovasc Magn Reson. 2022 Feb 7;24(1):11.
Results Reference
background
PubMed Identifier
23847253
Citation
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.
Results Reference
background
PubMed Identifier
26259581
Citation
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.
Results Reference
background
PubMed Identifier
24066038
Citation
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.
Results Reference
background
PubMed Identifier
33264359
Citation
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.
Results Reference
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Links:
URL
https://www.cardio-theranostics.com/
Description
CARDIO-THERANOSTICS is developing diagnostics and therapeutics for hemorrhagic myocardial infarction

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Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients

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