Cardiac MRI-guided Deferiprone Therapy for Acute Myocardial Infarction Patients

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Treatment Efficacy [Срок оценки: 6 months]

Вторичные конечные точки (5)

• Treatment Effect: Clinical Outcomes of Acute Heart Failure [Срок оценки: 6 months]
• Treatment Effect: Clinical Outcomes of Non-Fatal Cardiovascular morbidity [Срок оценки: 6 months]
• Safety and Tolerability - Rate of Discontinuation [Срок оценки: 6 months]
• Safety and Tolerability - Severe Side Effects [Срок оценки: 6 months]
• Safety and Tolerability - Reversibility of Side Effects without Treatment [Срок оценки: 6 months]

Критерии участия

Критерии включения

• Age 18-79 years
• Index Anterior wall STEMI
• Emergency coronary angiogram with primary PCI

Критерии исключения

• Prior history of MI / PCI / coronary artery bypass graft (CABG) within previous 1 year
• Patients with previous history of left ventricular ejection fraction (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 - ANC < 1.5 k/cumm
• History of Chronic Liver Disease
• Elevated hepatic enzymes (BOTH ALT and AST) > 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 Sponsor-Investigator or Delegate would preclude safe completion of the study or confound the anticipated benefit of deferiprone.
• Life expectancy of less than 1 year due to non-cardiac pathology

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• IU Methodist Hospital (IUHealth) — Indianapolis

Публикации

• 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. PMID 23403335
• 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. PMID 27903536
• 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. PMID 29680356
• 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. PMID 34991787
• 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. PMID 27894072
• 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. PMID 29242241
• 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. PMID 34368506
• 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. PMID 34261494

Идентификаторы

NCT: NCT05604131 · 13487

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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