Clinical trial NCT04803864: Study of Roxadustat in the Treatment of Acute Myocardial Infarction
Official title: A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Roxadustat in Patients With Acute ST Elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: ST Elevation Myocardial Infarction
Keywords: ST Elevation Myocardial Infarction
Roxadustat
Infarct Size
Cardiac MRI
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2021-03-18
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Depite successful primary percutaneous coronary intervention (PCI) and standardized medical treatment, prognosis of acute ST-elevation myocardial infarction patents are still a poor, with high morality and various complications such as heart failure. Roxadustat is a new drug targeting hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibition and has shown promising effect in reducing infarct size in pre-clinical studies.

This study aims to evaluate the efficacy and safety of early and short-term administration of roxadustat in the treatment of acute ST-elevation myocardial infarction.

Detailed description: This study is an open-label, paralleled, randomized controlled trial. It aims to evaluate the efficacy and safety of early and short-term administration of roxadustat in the treatment of acute ST-elevation myocardial infarction.

Eligibility criteria: Inclusion Criteria:

* Acute STEMI (ST segment elevation myocardial infarction) diagnosed by ST elevation
* Coronary angiography within 12 hours of symptom onset, with TIMI flow grade 0 - 1 of culprit vessel
* Primary PCI with TIMI flow grade 2 - 3 after successful intervention
* Capable and willing to provide informed consent and capable of completing study visits

Exclusion Criteria:

* Previous acute myocardial infarction history
* Cardiogenic Shock at admission
* Previously treated by roxadustat
* Contraindications of roxadustat treatment
* Contraindication of Cardiac MRI (e.g. eGFR \< 30 ml/min, pacemaker, metal prosthesis, etc.)

Primary outcomes:
measure: Infarct Size
timeFrame: 30 days
Secondary outcomes:
measure: MACE
timeFrame: 0 - 1 year
measure: Left Ventricular Function
timeFrame: 1 month, 6 months, 1 year
measure: Cardiac enzymes - peak concentration
timeFrame: 0 - 3 days
measure: Cardiac enzymes - Area under curve
timeFrame: 0 - 3 days
Other outcomes:
measure: Myocardial fibrosis
timeFrame: 30 days
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Ruiyan Zhang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Howell NJ, Tennant DA. The role of HIFs in ischemia-reperfusion injury. Hypoxia (Auckl). 2014 Jul 30;2:107-115. doi: 10.2147/HP.S49720. eCollection 2014.
citation: Sousa Fialho MDL, Abd Jamil AH, Stannard GA, Heather LC. Hypoxia-inducible factor 1 signalling, metabolism and its therapeutic potential in cardiovascular disease. Biochim Biophys Acta Mol Basis Dis. 2019 Apr 1;1865(4):831-843. doi: 10.1016/j.bbadis.2018.09.024. Epub 2018 Sep 25.
citation: Schreiber T, Salhofer L, Quinting T, Fandrey J. Things get broken: the hypoxia-inducible factor prolyl hydroxylases in ischemic heart disease. Basic Res Cardiol. 2019 Mar 11;114(3):16. doi: 10.1007/s00395-019-0725-2.
citation: Chen N, Hao C, Peng X, Lin H, Yin A, Hao L, Tao Y, Liang X, Liu Z, Xing C, Chen J, Luo L, Zuo L, Liao Y, Liu BC, Leong R, Wang C, Liu C, Neff T, Szczech L, Yu KP. Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis. N Engl J Med. 2019 Sep 12;381(11):1001-1010. doi: 10.1056/NEJMoa1813599. Epub 2019 Jul 24.
citation: Deguchi H, Ikeda M, Ide T, Tadokoro T, Ikeda S, Okabe K, Ishikita A, Saku K, Matsushima S, Tsutsui H. Roxadustat Markedly Reduces Myocardial Ischemia Reperfusion Injury in Mice. Circ J. 2020 May 25;84(6):1028-1033. doi: 10.1253/circj.CJ-19-1039. Epub 2020 Mar 24.
citation: Groenendaal-van de Meent D, den Adel M, Rijnders S, Krebs-Brown A, Kerbusch V, Golor G, Schaddelee M. The Hypoxia-inducible Factor Prolyl-Hydroxylase Inhibitor Roxadustat (FG-4592) and Warfarin in Healthy Volunteers: A Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction Study. Clin Ther. 2016 Apr;38(4):918-28. doi: 10.1016/j.clinthera.2016.02.010. Epub 2016 Mar 4.