Timing of Empagliflozin in Primary PCI: Pre-Reperfusion Versus Post-Reperfusion Versus Placebo in South Asian STEMI Patients

Обзор

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.

Подробное описание

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.

Echocardiograms, ultrasound images of the heart, are done at Day 3, Day 30, and Day 90 to measure how well the heart pumps blood. At least 120 participants at CMR-capable sites will have a cardiac MRI between Day 3 and Day 5 to confirm troponin findings.

A substudy measures empagliflozin levels in the blood at balloon inflation in all Group A participants. A smaller group has additional blood samples over 24 hours to study drug absorption. These measurements test whether higher drug levels at balloon inflation lead to lower heart injury.

The trial takes place at five heart centres in Pakistan: Peshawar Institute of Cardiology, Lady Reading Hospital, Rehman Medical Institute, and Hayatabad Medical Complex in Peshawar, and Kulsoom International Hospital in Islamabad.

An independent Data Safety Monitoring Board reviews safety at three points during the trial, checking for kidney problems, diabetic ketoacidosis, infections, or other serious side effects. The trial has rules to stop or pause if safety issues arise.

Enrollment runs from August 2026 to May 2027. Each participant is followed for 90 days, with final follow-up completed by August 2027. Results are expected by September 2027.

Primary analysis uses ANCOVA, accounting for differences such as heart attack location, diabetes, symptom duration, and hospital. A fixed-sequence testing hierarchy controls for false positive findings: Arm A compared to Arm C first, then Arm A to Arm B, then Arm B to Arm C.

Вмешательства

• Препарат empagliflozin
  Empagliflozin is an oral sodium-glucose cotransporter-2 (SGLT2) inhibitor administered in addition to guideline-directed medical therapy for acute ST-segment elevation myocardial infarction (STEMI). Participants randomized to the experimental groups receive empagliflozin according to the study protocol. In one experimental arm, empagliflozin is administered before primary percutaneous coronary intervention (PCI) (pre-reperfusion), whereas in the second experimental arm, it is administered immedi
• Препарат Placebo
  Participants randomized to the control arm receive matching placebo tablets that are identical in appearance, packaging, and administration schedule to empagliflozin. Placebo is administered in addition to guideline-directed medical therapy to maintain blinding throughout the study. The placebo regimen follows the same schedule as the active intervention without containing the active pharmaceutical ingredient.

Первичные конечные точки

• Log-Transformed High-Sensitivity Troponin-I Area Under the Curve (AUC) Over 0-48 Hours Post-Reperfusion [Срок оценки: 0-48 hours after successful reperfusion by primary PCI]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Пакистан · 1 центр

• Rehman Medical Institute — Peshawar

Идентификаторы

NCT: NCT07749014 · RMI/IRB-EC/2026/020

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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