Clinical trial NCT05604131: Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients
Official title: Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myocardial Infarction Type 1
Keywords: Acute Myocardial Infarction
Intramyocardial Hemorrhage
Deferiprone
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2022-11-03
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria

1. Age ≥ 18 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

Primary outcomes:
measure: Treatment Efficacy
timeFrame: 6 months
Secondary outcomes:
measure: Treatment Effect: Clinical Outcomes of Acute Heart Failure
timeFrame: 6 months
measure: Treatment Effect: Clinical Outcomes of Non-Fatal Cardiovascular morbidity
timeFrame: 6 months
measure: Safety and Tolerability - Rate of Discontinuation
timeFrame: 6 months
measure: Safety and Tolerability - Severe Side Effects
timeFrame: 6 months
measure: Safety and Tolerability - Reversibility of Side Effects without Treatment
timeFrame: 6 months
Other outcomes:
measure: Treatment Effect: Fat Infiltration
timeFrame: 6 months
Locations:
city: Indianapolis
country: United States
facility: Krannert Cardiovascular Research Center
state: Indiana
Study officials:
affiliation: Krannert Cardiovascular Research Center
name: Rohan Dharmakumar, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Krannert Cardiovascular Research Center
name: Keyur P Vora, MD FACP FACC
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.