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

NCT07749014 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: RMI/IRB-EC/2026/020
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ST-elevation Myocardial Infarction (STEMI); Coronary Artery Disease; Acute Myocardial Infarction (AMI)

Keywords

Empagliflozin; SGLT2 Inhibitor; ST-elevation myocardial infarction; Primary Percutaneous Coronary Intervention; Primary PCI; Ischemia-Reperfusion Injury; Myocardial Infarction; Troponin I; Cardioprotection; South Asian Population

Outcome Measures

Primary Outcomes (1)

• Log-Transformed High-Sensitivity Troponin-I Area Under the Curve (AUC) Over 0-48 Hours Post-Reperfusion

  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

  0-48 hours after successful reperfusion by primary PCI

Study Arms (3)

Pre-reperfusion Empagliflozin

EXPERIMENTAL

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.

Drug: empagliflozin; Drug: Placebo

Post-reperfusion Empagliflozin

EXPERIMENTAL

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.

Drug: empagliflozin; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

empagliflozin DRUG

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 immediately after successful reperfusion by primary PCI (post-reperfusion). All subsequent dosing, follow-up, and safety monitoring are conducted according to the protocol.

Also known as: Jardiance

Post-reperfusion Empagliflozin; Pre-reperfusion Empagliflozin

Placebo DRUG

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.

Placebo; Post-reperfusion Empagliflozin; Pre-reperfusion Empagliflozin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rehman Medical Institute - RMI: lead
• Michigan State University: collaborator

Study Sites (1)

Rehman Medical Institute

Peshawar, Khyber Pakhtun Khwa, 25000, Pakistan

Location

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Coronary Artery Disease; Reperfusion Injury; Myocardial Infarction

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Postoperative Complications

Study Officials

• Miqdad A Khan, MD, FACC, FISCI, FSCAI, FACP

  Rehman Medical Institute

  PRINCIPAL INVESTIGATOR

• Herbert D Aronow, MD, MPH, MSCAI, FACC, MSVM

  Michigan State University College of Human Medicine

  STUDY CHAIR

• Ashraf S Niazi, MBBS, FRCP

  Northampton General Hospital, UK

  STUDY DIRECTOR

Central Study Contacts

Syed M Rayyan, MBBS

CONTACT

+923369949269; drsmuhammadrayyan@gmail.com

Hammad Saif, MBBS

CONTACT

+923349903737; hammadsaif7690@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: HOD & Consultant Cardiologist

Model Details: Three-arm, double-dummy parallel design. Every participant receives one pre-PCI and one post-PCI dose pack on an identical schedule, so administration sequence cannot reveal allocation. Arm A: empagliflozin 25 mg loading immediately after randomization, before cath-lab transfer (no PCI delay), plus matched placebo post-PCI. Arm B: matched placebo pre-PCI plus empagliflozin 25 mg loading within 2 hours after successful PCI. Arm C: matched placebo at both timepoints. All arms then continue blinded empagliflozin 10 mg once daily or matched placebo for 90 days, so total drug exposure is equal across active arms and only loading-dose timing differs. Randomization is 1:1:1 via variable block sizes, stratified by site, diabetes status, and infarct territory.

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 6, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: August 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: Individual participant data, the statistical analysis code, and the Statistical Analysis Plan will become available beginning 9 months after publication of the primary results manuscript and will remain available for 36 months thereafter.
• Access Criteria: Available to qualified researchers who submit a scientifically sound research proposal to the Coordinating Principal Investigator. Requestors must provide institutional affiliation, a written proposal, and evidence of their own institutional ethics approval. Access is granted only after execution of a data-sharing agreement with the coordinating site (Rehman Medical Institute, Peshawar) and is limited to de-identified individual participant data, the statistical analysis code, and the Statistical Analysis Plan, for the stated research purpose only.

Locations

PA (1)