Pirfenidone Treat Myocardial Fibrosis After Acute Myocardial Infarction (PROTECT-AMI)

November 7, 2022 updated by: Shanghai Zhongshan Hospital

A Study of Pirfenidone in the Treatment of Myocardial Fibrosis After Acute Myocardial Infarction: a Phase II Prospective, Randomized, Double-blind，Placebo Controlled Clinical Trial

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

It plays an important role in preventing or delaying the occurrence of heart failure after myocardial infarction.However,even if the blood supply of infarct related vessels is restored, the immune injury, inflammatory response and RAAS activation caused by apoptotic and necrotic cardiomyocytes after myocardial infarction will still directly lead to a series of pathophysiological changes and aggravate cardiac remodeling. Based on the above targets β Receptor blockers, ACEI / ARB / Arni and aldosterone receptor antagonists have become the cornerstone of drug therapy for cardiac remodeling after myocardial infarction. However, myocardial fibrosis also plays an important role in the process of cardiac remodeling after myocardial infarction. Ischemic death of cardiomyocytes after myocardial infarction can induce repair response, and the damaged tissue is replaced by fibrotic scar produced by fibroblasts and myofibroblasts. Although the initial reparative fibrosis is very important to prevent ventricular wall rupture, excessive fibrosis and reactive fibrosis in non infarcted areas, including myocardial interstitial and perivascular fibrosis, will cause changes in cardiac morphology and biomechanics, further aggravate cardiac remodeling, damage cardiac function, and eventually lead to heart failure. Therefore, inhibition of reactive fibrosis in non infarcted areas is an important supplement to the current treatment of traditional anti cardiac remodeling drugs. In order to reduce the degree of reactive fibrosis in non infarct areas, a potentially feasible method is to inhibit the signal pathway promoting fibrosis. TGF- β Signal pathway plays an important role in promoting fibrosis signal pathway. It can promote the proliferation of fibroblasts, the differentiation and transfer of myofibroblasts, the deposition of collagen and the survival of myofibroblasts, so it can inhibit TGF- β Signal pathway is an effective method to inhibit myocardial fibrosis.

Pirfenidone (PFD) is TGF- β The inhibitor can be used to delay the progression of idiopathic pulmonary fibrosis (IPF). Animal experiments also show that PFD can inhibit TGF- β Reduce myocardial fibrosis and improve the ability of myocardial contraction and relaxation. In the mouse model of dilated cardiomyopathy, it can effectively inhibit the pathological process of dilated cardiomyopathy, improve the degree of cardiac dilation and ventricular wall thickness. Preclinical studies have shown that PFD can inhibit myocardial fibrosis and protect the heart. A recently published phase II clinical study showed that compared with placebo, PFD significantly reduced EF value, preserved myocardial extracellular volume (ECV) and improved myocardial fibrosis in patients with heart failure (HFPEF). In view of the above background, we propose a research assumption: for patients after AMI, PFD drug intervention on the basis of standard treatment may achieve the effect of inhibiting myocardial fibrosis in non infarcted areas, so as to prevent or delay the occurrence of ventricular remodeling and heart failure after myocardial infarction, improve the quality of life and improve the prognosis of patients

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • Shanghai Zhongshan Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Those who do not meet any of the inclusion criteria.
  2. Patients with non acute anterior myocardial infarction.
  3. Patients without PCI after myocardial infarction.
  4. Glomerular filtration rate (CKD-EPI equation) < 30 ml / min / 1.73 m2.
  5. Moderate or severe liver cirrhosis, or TBIL > 2 times ULN, ALT or AST > 3 times ULN caused by non cardiac reasons.
  6. Patients with malignant tumors.
  7. Patients with dysphagia or clinical signs of absorption disorder or requiring parenteral nutrition.
  8. Patients with active peptic ulcer.
  9. Severe pulmonary hypertension (pulmonary systolic pressure > 70mmhg).
  10. 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.
  11. Allergic to the test drug or its components (e.g., lactose).
  12. Major surgery is planned during treatment.
  13. Women who are pregnant, breastfeeding or planning to become pregnant during the trial.
  14. Women of childbearing age are unwilling or unable to use highly effective contraceptive methods 28 days before administration or 3 months after administration.
  15. According to the researchers, the patients had alcohol or drug abuse.
  16. Patients with mental illness.
  17. Participate in clinical trials of other drugs.
  18. The researchers judged the participants who were unwell.
  19. Patients who need to use Nintedanib, pirfenidone and Amifostine at the same time.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pirfenidone group
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
pirfenidone capsules were added to patients receiving basic treatment
Placebo Comparator: Placebo group
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
placebo oral capsules were added to patients receiving basic treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes of the subjects'ECV
Time Frame: 52week
Compare the ECV of subjects
52week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular death
Time Frame: 52week
Number of participants with cardiovascular death
52week
Admission for heart failure
Time Frame: 52week
Number of participants for heart failure
52week
Death
Time Frame: 52week
collect the case of death
52week
Changes of LVE
Time Frame: 52week
compare the LVEF of the subjects
52week
Changes of NT-proBNP
Time Frame: 52week
compare the NT-proBNP of the subjects
52week
Changes of ST2
Time Frame: 52week
compare the ST2 of the subjects
52week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Zhongshan Hospital

Collaborators

Beijing Continent Pharmaceutical Co, Ltd.

Investigators

  • Principal Investigator: Junbo Ge, Doctor, Shanghai Zhongshan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2022

Primary Completion (Anticipated)

May 1, 2024

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

August 18, 2022

First Submitted That Met QC Criteria

September 7, 2022

First Posted (Actual)

September 8, 2022

Study Record Updates

Last Update Posted (Actual)

November 10, 2022

Last Update Submitted That Met QC Criteria

November 7, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHZS- F647-PIN-202201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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