Pirfenidone Treat Myocardial Fibrosis After Acute Myocardial Infarction

NCT05531955 | Unknown Phase 2

• 1 other identifier: SHZS- F647-PIN-202201
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Acute myocardial infarction (AMI) is myocardial necrosis caused by acute and continuous ischemia and hypoxia of coronary artery. It can be complicated with arrhythmia, shock or heart failure, which is often life-threatening. The disease is the most common in Europe and the United States, where about 1.5 million people suffer from myocardial infarction every year. China has shown an obvious upward trend in recent years, with at least 500000 new cases every year and at least 2 million current cases . At present, China has a high incidence rate of heart failure after myocardial infarction. The incidence of heart failure within 7 days after myocardial infarction is 19.3%, and the incidence of heart failure from 30 days to 6.7 years after myocardial infarction is 13.1%\~37.5%. The incidence of heart failure after myocardial infarction significantly increases the risk of short-term and long-term death, and the prognosis is poor. At present, there is a lack of unified guidance and norms for the diagnosis, treatment and prevention and control strategies of heart failure after myocardial infarction. Cardiac remodeling is the basic pathological process of heart failure after myocardial infarction, and it is also one of the main factors affecting the prognosis of patients. Studies have shown that 30% of AMI have ventricular remodeling 6 months after percutaneous coronary intervention (PCI), and the risk of ventricular remodeling in anterior wall myocardial infarction is the highest. According to foreign literature data, the probability of ventricular remodeling after anterior wall acute myocardial infarction is about 13%, which is 1.9 times higher than that in other parts.Opening the infarct related coronary artery early can save the dying myocardium, reduce the infarct myocardial area and reduce the loss of cardiomyocytes.

Conditions

Myocardial Fibrosis

Outcome Measures

Primary Outcomes (1)

• Changes of the subjects'ECV

  Compare the ECV of subjects

  52week

Secondary Outcomes (6)

• Cardiovascular death

  52week

• Admission for heart failure

  52week

• Death

  52week

• Changes of LVE

  52week

• Changes of NT-proBNP

  52week

Study Arms (2)

Pirfenidone group

EXPERIMENTAL

Drug name:Pirfenidone Dosage Form:capsule Dosage:200mg three times a day in 1st week;400mg three times a day in 2ndweek;600mg three times a day in 3rd week\~52th week.

Drug: Pirfenidone Oral Capsule

Placebo group

PLACEBO COMPARATOR

Drug name:Placebo Dosage Form:capsule Dosage:200mg three times a day in 1st week;400mg three times a day in 2ndweek;600mg three times a day in 3rd week\~52th week.

Other: Placebo Oral Capsule

Interventions

Pirfenidone Oral Capsule DRUG

pirfenidone capsules were added to patients receiving basic treatment

Pirfenidone group

Placebo Oral Capsule OTHER

placebo oral capsules were added to patients receiving basic treatment

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 \~ 80 years old (including 18 and 80 years old), regardless of gender.
• Patients with acute anterior myocardial infarction 2-4 weeks after PCI.
• NT proBNP ≥ 800 pg / ml in patients with sinus rhythm and 2400 pg / ml in patients with atrial fibrillation.
• LVEF \<50%.
• The patients volunteered to participate in the trial, with good compliance and the ability to understand and sign the informed consent before the study

You may not qualify if:

• Patients with non acute anterior myocardial infarction.
• Patients without PCI after myocardial infarction.
• Glomerular filtration rate (CKD-EPI equation) \< 30 ml / min / 1.73 m2.
• Moderate or severe liver cirrhosis, or TBIL \> 2 times ULN, ALT or AST \> 3 times ULN caused by non cardiac reasons.
• Patients with malignant tumors.
• Patients with dysphagia or clinical signs of absorption disorder or requiring parenteral nutrition.
• Patients with active peptic ulcer.
• Severe pulmonary hypertension (pulmonary systolic pressure \> 70mmhg).
• Other diseases or complications that may affect the participation in the trial or put the patient at risk based on the judgment of the investigator.
• Allergic to the test drug or its components (e.g., lactose).
• Major surgery is planned during treatment.
• Women who are pregnant, breastfeeding or planning to become pregnant during the trial.
• Women of childbearing age are unwilling or unable to use highly effective contraceptive methods 28 days before administration or 3 months after administration.
• According to the researchers, the patients had alcohol or drug abuse.
• Patients with mental illness.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Beijing Continent Pharmaceutical Co, Ltd.: collaborator

Study Sites (1)

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, 200030, China

Location

Related Publications (9)

• Talman V, Ruskoaho H. Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration. Cell Tissue Res. 2016 Sep;365(3):563-81. doi: 10.1007/s00441-016-2431-9. Epub 2016 Jun 21.

  PMID: 27324127 BACKGROUND

• Prabhu SD, Frangogiannis NG. The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. Circ Res. 2016 Jun 24;119(1):91-112. doi: 10.1161/CIRCRESAHA.116.303577.

  PMID: 27340270 BACKGROUND

• Lee HC, Park JS, Choe JC, Ahn JH, Lee HW, Oh JH, Choi JH, Cha KS, Hong TJ, Jeong MH; Korea Acute Myocardial Infarction Registry (KAMIR) and Korea Working Group on Myocardial Infarction (KorMI) Investigators. Prediction of 1-Year Mortality from Acute Myocardial Infarction Using Machine Learning. Am J Cardiol. 2020 Oct 15;133:23-31. doi: 10.1016/j.amjcard.2020.07.048. Epub 2020 Jul 26.

  PMID: 32811651 BACKGROUND

• Dondo TB, Hall M, Munyombwe T, Wilkinson C, Yadegarfar ME, Timmis A, Batin PD, Jernberg T, Fox KA, Gale CP. A nationwide causal mediation analysis of survival following ST-elevation myocardial infarction. Heart. 2020 May;106(10):765-771. doi: 10.1136/heartjnl-2019-315760. Epub 2019 Nov 15.

  PMID: 31732655 BACKGROUND

• Lewis GA, Dodd S, Clayton D, Bedson E, Eccleson H, Schelbert EB, Naish JH, Jimenez BD, Williams SG, Cunnington C, Ahmed FZ, Cooper A, Rajavarma Viswesvaraiah, Russell S, McDonagh T, Williamson PR, Miller CA. Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial. Nat Med. 2021 Aug;27(8):1477-1482. doi: 10.1038/s41591-021-01452-0. Epub 2021 Aug 12.

  PMID: 34385704 BACKGROUND

• Graziani F, Lillo R, Crea F. Rationale for the Use of Pirfenidone in Heart Failure With Preserved Ejection Fraction. Front Cardiovasc Med. 2021 Apr 22;8:678530. doi: 10.3389/fcvm.2021.678530. eCollection 2021.

  PMID: 33969025 BACKGROUND

• Lewis GA, Schelbert EB, Naish JH, Bedson E, Dodd S, Eccleson H, Clayton D, Jimenez BD, McDonagh T, Williams SG, Cooper A, Cunnington C, Ahmed FZ, Viswesvaraiah R, Russell S, Neubauer S, Williamson PR, Miller CA. Pirfenidone in Heart Failure with Preserved Ejection Fraction-Rationale and Design of the PIROUETTE Trial. Cardiovasc Drugs Ther. 2019 Aug;33(4):461-470. doi: 10.1007/s10557-019-06876-y.

  PMID: 31069575 BACKGROUND

• Nguyen DT, Ding C, Wilson E, Marcus GM, Olgin JE. Pirfenidone mitigates left ventricular fibrosis and dysfunction after myocardial infarction and reduces arrhythmias. Heart Rhythm. 2010 Oct;7(10):1438-45. doi: 10.1016/j.hrthm.2010.04.030. Epub 2010 Apr 28.

  PMID: 20433946 BACKGROUND

• Li C, Han R, Kang L, Wang J, Gao Y, Li Y, He J, Tian J. Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-alpha in myocardial infarction-induced cardiac fibrosis. Sci Rep. 2017 Jan 16;7:40523. doi: 10.1038/srep40523.

  PMID: 28091615 BACKGROUND

MeSH Terms

Interventions

pirfenidone

Study Officials

• Junbo Ge, Doctor

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2022
• First Posted: September 8, 2022
• Study Start: August 5, 2022
• Primary Completion: May 1, 2024
• Study Completion: June 1, 2024
• Last Updated: November 10, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)