Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients

Acute Myocardial Infarction Type 1 Clinical Trial

— MIRON-DFP  

Official title:

Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05604131
• Other study ID #: 13487
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 8, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: March 2024
• Source: Indiana University
• Contact: Chandana Saha, PhD
• Phone: (317) 274-0985
• Email: csaha[@]iu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria

1. Age 18-79 years

2. Index STEMI, based on American Heart Association guidelines diagnostic criteria

3. Coronary angiogram with primary PCI to occur irrespective of the duration of the symptoms.

Exclusion Criteria

1. Prior history of MI / PCI / CABG

2. Patients with history of 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 of ANC < 1.0 x 109 /L

10. Elevated hepatic enzymes (ALT and/or AST) > 2 times of upper normal limit and not taking medications for chronic liver disease

11. Patients with iron storage disease (hemochromatosis, thalassemia) or who are already treated with iron chelators

12. 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 LIPOMED.

13. Life expectancy of less than 1 year due to non-cardiac pathology

Related Conditions & MeSH terms

• Acute Myocardial Infarction Type 1
• Infarction
• Myocardial Infarction

Intervention

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
Deferiprone placebo is the non-medicated formulation for a control arm of the study groups.

Locations

Country	Name	City	State
United States	Krannert Cardiovascular Research Center	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Rohan Dharmakumar

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	Treatment Efficacy	Percentage reduction of hemorrhagic zone iron content by cardiac magnetic resonance at 6 months relative to baseline	6 months
Secondary	Treatment Effect: Clinical Outcomes of Acute Heart Failure	The proportion of subjects who experience an acute heart failure event	6 months
Secondary	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
Secondary	Safety and Tolerability - Rate of Discontinuation	Rate of discontinuation of therapy due to side effects	6 months
Secondary	Safety and Tolerability - Severe Side Effects	Rate of severe side effects requiring hospitalization, extension of length-of-stay.	6 months
Secondary	Safety and Tolerability - Reversibility of Side Effects without Treatment	Percentage of Reversible of Side Effects without treatment	6 months

External Links

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