Timing of Empagliflozin in Primary PCI: Pre-Reperfusion Versus Post-Reperfusion Versus Placebo in South Asian STEMI Patients
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 480
- 试验地点
- 1
- 主要终点
- Log-Transformed High-Sensitivity Troponin-I Area Under the Curve (AUC) Over 0-48 Hours Post-Reperfusion
研究概览
简要总结
The goal of this clinical trial is to learn if giving the drug empagliflozin before versus after a heart procedure called primary PCI (percutaneous coronary intervention) affects how much heart muscle is damaged during a heart attack. Primary PCI is a procedure that opens blocked heart arteries using a small balloon and stent. While this procedure saves lives, it can also cause extra injury to the heart muscle when blood flow returns. Researchers want to know if empagliflozin given before the procedure can protect the heart better than giving it after the procedure.
The main questions this trial aims to answer are:
Does giving empagliflozin before the PCI procedure reduce heart muscle injury more than a placebo (a look-alike pill with no active drug)?
Does giving empagliflozin before PCI protect the heart better than giving it after PCI?
Does empagliflozin given after PCI reduce heart muscle injury compared with a placebo?
Researchers will compare three groups of participants to see if the timing of empagliflozin matters:
Group A receives empagliflozin before the PCI procedure
Group B receives empagliflozin after the PCI procedure
Group C receives a placebo at both times
All three groups will continue taking their assigned study pills for 90 days.
Participants in this study are adults aged 18 to 75 from South Asian backgrounds (Pakistani, Indian, Bangladeshi, Sri Lankan, or Nepali) who are having their first heart attack and are scheduled for the PCI procedure within 12 hours of their symptoms starting.
Participants will:
Take a single loading dose of the study pill or placebo right before the PCI procedure
Take a single loading dose of the study pill or placebo within 2 hours after the PCI procedure
Continue taking the study pill or placebo once daily for 90 days
Have blood samples taken 6 times over 48 hours to measure heart muscle injury
Have heart function tests at Day 3, Day 30, and Day 90 (echocardiograms, which are ultrasound pictures of the heart)
Have a special heart scan (CMR) between Day 3 and Day 5 for some participants to get detailed pictures of the heart muscle
Complete 90 days of follow-up with clinic visits and tests
Researchers will measure heart muscle injury using a blood test called high-sensitivity troponin. This test measures a protein that is released when heart muscle is damaged. The total amount of this protein released over 48 hours will tell researchers how much heart muscle was injured.
详细描述
Primary PCI opens blocked heart arteries during a heart attack but can cause additional injury when blood flow returns. This is called reperfusion injury and accounts for up to half of the final heart damage. No drug given at the time of this procedure has been proven to reduce this injury in routine practice.
Laboratory studies suggest empagliflozin, a drug approved for diabetes and heart failure, may protect the heart when given before blood flow is restored. It may work by reducing harmful chemical changes inside heart cells, protecting mitochondria, and lowering inflammation. However, it is not known if empagliflozin must be given before the procedure to work, or if giving it afterward works just as well. Prior large studies gave empagliflozin days after heart attacks and could not test this question. Smaller pre-procedure studies had mixed results.
This trial answers one main question: does the timing of empagliflozin matter for protecting the heart during a heart attack? It compares giving the drug before the procedure, within 2 hours after the procedure, or a placebo. This is a Phase II trial designed to provide information needed to plan a larger future trial.
The trial enrolls 480 South Asian adults aged 18 to 75 having their first heart attack and scheduled for primary PCI within 12 hours of symptom onset. Participants are randomly assigned to one of three groups. Group A receives empagliflozin 25 mg before the procedure and placebo afterward. Group B receives placebo before and empagliflozin 25 mg within 2 hours after successful PCI. Group C receives placebo at both times. All groups continue study pills once daily for 90 days. The double-dummy design keeps participants and researchers unaware of group assignments.
Blood samples are taken at the procedure and at 6, 12, 24, and 48 hours afterward. These are sent to a central lab to measure troponin, a protein released when heart muscle is damaged. The total troponin released over 48 hours is the main measure of heart injury. Additional blood tests measure other heart function and inflammation markers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Data entry staff and the analysis biostatistician are also masked to treatment allocation for the duration of the trial. Only the site pharmacist, who prepares and dispenses the blinded dose kits, and an independent statistician, who generates the randomization sequence and performs interim DSMB analyses, have access to unblinded allocation; neither is involved in patient care, outcome assessment, or data analysis.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years at presentation.
- •South Asian ethnicity (Pakistani, Indian, Bangladeshi, Sri Lankan, or Nepali origin).
- •First STEMI: ST-elevation ≥1 mm in ≥2 contiguous limb leads, or ≥2 mm in ≥2 contiguous precordial leads, or new LBBB with consistent presentation.
- •Symptom onset to hospital arrival ≤12 hours.
- •Scheduled for primary PCI with intent to perform balloon inflation and stenting.
- •eGFR ≥45 mL/min/1.73m² (CKD-EPI) from point-of-care creatinine at presentation.
- •Able to take oral medication (or crushed tablet with water), swallowing ability confirmed by treating nurse.
- •Written informed consent from patient or legally authorised representative
排除标准
- •Cardiogenic shock at presentation (Killip IV: SBP <90 mmHg despite volume, requiring vasopressors, IABP, or mechanical circulatory support).
- •Type 1 diabetes mellitus.
- •SGLT2 inhibitor use within 3 months of presentation.
- •Active urinary tract infection or genital mycotic infection.
- •eGFR <45 mL/min/1.73m² at presentation.
- •Severe hepatic impairment (Child-Pugh Class C).
- •Known hypersensitivity to empagliflozin or any SGLT2 inhibitor.
- •History of diabetic ketoacidosis (euglycaemic or classical) at any time.
- •Pregnancy, breastfeeding, or refusal of contraception (women of childbearing potential).
- •Prior myocardial infarction or prior coronary revascularisation.
- •Left main culprit artery as the infarct-related vessel.
- •Rescue PCI after fibrinolysis in the current presentation.
- •Severe multivessel disease with anticipated need for urgent CABG within 48 hours.
- •Cardiac arrest with coma (GCS <8) at presentation consent not obtainable and metabolic state unpredictable.
- •Significant metabolic abnormality precluding oral drug: severe vomiting, nil-by-mouth status, or frank dehydration with SBP <100 mmHg on arrival.
- •Concurrent participation in another interventional clinical trial.
- •Life expectancy <6 months from a non-cardiac cause.
- •Expected inability to attend the 90-day follow-up visit.
研究组 & 干预措施
Pre-reperfusion Empagliflozin
Participants receive a single empagliflozin 25 mg loading dose immediately after randomization, before cath-lab transfer, with no delay to primary PCI, followed by a matched placebo dose within 2 hours after PCI. Empagliflozin 10 mg once daily is then continued for 90 days, in addition to guideline-directed standard care.
干预措施: Placebo (Drug)
Post-reperfusion Empagliflozin
Participants receive a matched placebo dose before primary PCI, followed by a single empagliflozin 25 mg loading dose within 2 hours after successful PCI. Empagliflozin 10 mg once daily is then continued for 90 days, in addition to guideline-directed standard care.
干预措施: Placebo (Drug)
Placebo
Participants receive matched placebo before primary PCI and again within 2 hours after PCI, followed by matched placebo once daily for 90 days, in addition to guideline-directed standard care.
干预措施: Placebo (Drug)
Post-reperfusion Empagliflozin
Participants receive a matched placebo dose before primary PCI, followed by a single empagliflozin 25 mg loading dose within 2 hours after successful PCI. Empagliflozin 10 mg once daily is then continued for 90 days, in addition to guideline-directed standard care.
干预措施: empagliflozin (Drug)
Pre-reperfusion Empagliflozin
Participants receive a single empagliflozin 25 mg loading dose immediately after randomization, before cath-lab transfer, with no delay to primary PCI, followed by a matched placebo dose within 2 hours after PCI. Empagliflozin 10 mg once daily is then continued for 90 days, in addition to guideline-directed standard care.
干预措施: empagliflozin (Drug)
结局指标
主要结局
Log-Transformed High-Sensitivity Troponin-I Area Under the Curve (AUC) Over 0-48 Hours Post-Reperfusion
时间窗: 0-48 hours after successful reperfusion by primary PCI
The primary outcome is the total myocardial injury burden measured as the log-transformed area under the concentration-time curve (AUC) of high-sensitivity Troponin-I over the first 48 hours following successful reperfusion by primary percutaneous coronary intervention (PCI). Troponin-I concentrations will be measured at 0, 6, 12, 24, and 48 hours post-reperfusion using a single assay platform at a central biomarker core laboratory. The AUC will be calculated using the trapezoidal method and compared between the pre-reperfusion empagliflozin, post-reperfusion empagliflozin, and placebo groups. Time Frame: 0, 6, 12, 24, and 48 hours after successful reperfusion by primary PCI
次要结局
未报告次要终点
研究者
Miqdad Ali Khan
HOD & Consultant Cardiologist
Rehman Medical Institute - RMI