Study of Roxadustat in the Treatment of Acute Myocardial Infarction

ST Elevation Myocardial Infarction Clinical Trial

— ROXAMI  

Official title:

A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Roxadustat in Patients With Acute ST Elevation Myocardial Infarction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04803864
• Other study ID #: SHDC2020CR2023B
• Status: Recruiting
• Phase: Phase 2
• Start date: June 10, 2021
• Est. completion date: August 31, 2023

Study information

• Verified date: August 2021
• Source: Ruijin Hospital
• Contact: Shuo Feng, M.D.
• Phone: +86 15921388296
• Email: fengshuorv[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 158
• Est. completion date: August 31, 2023
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Drug:
• Roxadustat
Orally 100mg, 3 times per week for 2 weeks First dose administered immediately after successful PCI.

Locations

Country	Name	City	State
China	Ruijin Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View 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. — View 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. — View Citation

Howell NJ, Tennant DA. The role of HIFs in ischemia-reperfusion injury. Hypoxia (Auckl). 2014 Jul 30;2:107-115. eCollection 2014. Review. — View Citation

Schreiber T, Salhöfer 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. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Myocardial fibrosis	Fibroblast activation protein inhibitor (FAPI) tracer uptake in myocardium if selected patient underwent spontaneous PET/MR scan	30 days
Primary	Infarct Size	Infarct size as a percentage of LV mass measured on delayed-enhanced CMR imaging 30 days post-MI compared to control	30 days
Secondary	MACE	Major adverse cardiovascular events (MACE) within 1 year follow-up.	0 - 1 year
Secondary	Left Ventricular Function	Left ventricular end diastolic volume (LVEDV), Left ventricular end systolic volume (LVESV), Left ventricular ejection fraction (LVEF) changes during 1 year follow-up	1 month, 6 months, 1 year
Secondary	Cardiac enzymes - peak concentration	Peak Plasma Concentration (Cmax) of CK-MB, TnI and CK	0 - 3 days
Secondary	Cardiac enzymes - Area under curve	Area under the plasma concentration versus time curve (AUC) of CK-MB, TnI and CK	0 - 3 days