Prehospital Pulse-dose Glucocorticoid in Patients With ST-segment Elevation Myocardial Infarction 2 - The PULSE-MI 2 Trial (PULSE-MI 2)

April 20, 2026 updated by: Thomas Engstrom

BACKGROUND Myocardial reperfusion with the use of primary percutaneous coronary intervention (PCI) including stent implantation is the most efficacious treatment for patients with (STEMI) and improves prognosis significantly. Due to continuous improvements in the treatment, the mortality for patients with STEMI has decreased dramatically, but despite these improvements, the mortality rate seems to have reached a plateau at around 10% within 1 year. In addition, 10% develop clinical heart failure with a per se 50% mortality rate within 5 years. Moreover, congestive heart failure is associated with a highly impaired quality of life due to fatigue dyspnea and reduced exercise capacity. Thus, there is a need for further improvement in the treatment to drive the event rates further down. One such key target is reducing the damage to the heart muscle (infarct size) to preserve the heart function and prevent mortality and heart failure. One major driver of infarct size and mortality is reperfusion injury which may account for up to 50% of the damaged myocardium. Reperfusion injury occurs within the first minutes to hours after the restoration of the blood flow in the occluded artery and reperfusion therapy can therefore be considered a "double-edged sword", since the ischemic injury may additionally be worsened by reperfusion injury. However, the phenomenon of reperfusion injury is not completely understood, and no preventive treatments exist. Multiple pathophysiological factors may contribute to reperfusion injury of which inflammation has been described as a key factor.

Inflammation is induced immediately after the onset of acute myocardial ischemia and is subsequently exacerbated following reperfusion. Hence, inflammation per se may drive excessive cardiomyocyte death resulting in decreased contractility and increased infarct size post-STEMI. Moreover, in the course following STEMI and subsequently reperfusion, the myocardium starts healing and scarring resulting in remodelling of the ventricle potentially causing either compensatory hypertrophy or thinning of the myocardium, which may lead to reduced left ventricle ejection fraction (LVEF) and heart failure. Of note, inflammation plays a critical role in ventricular remodeling post-AMI, thus inflammation in relation to reperfusion injury may extend myocardial damage following STEMI.

Glucocorticoids are crucial in the regulation of the systemic inflammatory response and may therefore be beneficial in limiting myocardial injury following STEMI. We previously conducted the phase II randomized, placebo-controlled PULSE-MI trial (Nov 2022-Oct 2023) in 742 prehospital STEMI patients, showing pulse-dose glucocorticoid was safe and improved LVEF, infarct size, and microvascular obstruction, with a trend toward lower 3-month mortality. However, as the trial was not powered for clinical outcomes, it remains unproven whether this treatment reduces post-STEMI mortality. Thus, the aim of this prospective, randomized trial is to evaluate the effect of prehospital pulse-dose glucocorticoid on all-cause mortality in patients with STEMI.

To reduce the degree of inflammation effectively and adequately, intervention is to be made as soon as possible as close to initiation of ischemia, as recognized from patients' symptom debut, and before revascularization with primary PCI in the prehospital setting since the effect is more pronounced if the treatment is initiated early after the onset of STEMI. In addition to reperfusion induced inflammation, ischemia itself, immediately after occlusion of the artery, induces inflammation. Hence, initiation of the intervention in the ambulance is needed to harvest the potentially beneficial effects of pulse glucocorticoid therapy as soon as possible. Thus, by performing intervention in the pre-hospital setting, the investigators expect that participation in the trial will have the potential to produce a direct clinically relevant benefit for the patient resulting in reduced all-cause mortality in patients with STEMI.

HYPOTHESIS In patients with STEMI undergoing primary PCI, 250 mg methylprednisolone administrated in the pre-hospital setting reduces all-cause mortality.

SAMPLE SIZE The primary endpoint is all-cause mortality one year after the last patient has been included. The median follow-up of the trial is expected to be 3 years and minimum follow-up of 1 year. As an estimate based on findings from the PULSE-MI trial and the DANAMI-3 trial, the estimated event rate of in the placebo arm is 9% during follow-up. Glucocorticoid is expected to reduce all-cause mortality corresponding to a hazard ratio of 0.77. To demonstrate the reduction in the primary outcome with an 80% power at a 5% significance level, 2602 patients in each treatment arm is needed, thus 5204 patients in total. The primary analyses will be intention to treat principle

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

5204

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Aalborg, Denmark
        • Not yet recruiting
        • Aalborg University Hospital
        • Contact:
          • Ashkan Eftekhari, MD, PhD
          • Phone Number: +4597664465
          • Email: asef@rn.dk
      • Aarhus, Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Rigshospitalet
        • Contact:
        • Sub-Investigator:
          • Ben Elezi, MD
        • Sub-Investigator:
          • Jasmine M Marquard, MD
        • Sub-Investigator:
          • Thomas Engstrøm, MD, PhD, DMSc
      • Odense, Denmark
        • Not yet recruiting
        • Odense University Hospital
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18 years including fertile women
  • Acute onset of chest pain with < 24 hours duration

  • STEMI as characterized on electrocardiogram (ECG) by one of the following:

    1. at least two contiguous leads with ST-segment elevation ≥2.5 mm in men < 40 years, ≥2 mm in men ≥40 years, or ≥1.5 mm in women in leads V2-V3 and/or ≥1 mm in the other leads,
    2. presumed new left bundle branch block with ≥1 mm concordant ST-segment elevation in leads with a positive QRS complex, or concordant ST-segment depression ≥1 mm in V1-V3, or discordant ST-segment elevation ≥5 mm in leads with a negative QRS complex
    3. Isolated ST depression ≥0.5 mm in leads V1-V3 indicating posterior acute myocardial infarction (AMI)
    4. ST-segment depression ≥1 mm in eight or more surface leads, coupled with ST-segment elevation in aVR and/or V1 suggesting left main-, or left main equivalent- coronary obstruction

Exclusion Criteria:

  • Suspected other type I acute myocardial infarction at time of potential randomization
  • Initial presentation with cardiac arrest (out of hospital cardiac arrest)
  • Known allergy to glucocorticoid

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 0.9% NaCl
Drug: NaCl (0,9%)
The placebo will be 0.9% NaCl in 4 mL ampoules. The infusion of both study medicine and placebo will be done over a period of 5 minutes during transportation.
Active Comparator: 250 mg methylprednisolone
Drug: Methylprednisolone 250 mg
The active study medicine is 2 x 125 mg/2 mL Solu-Medrol, a total of 250 mg/4 mL, which comes as a sterile powder with preservative free isotonic NaCl as diluent. The medicine takes 30 to 60 sec-onds to mix and needs to be used within 48 hours when opened. The infusion of both study medicine and placebo will be done over a period of 5 minutes during transportation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
All-cause mortality
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient

Secondary Outcome Measures

Outcome Measure
Time Frame
Cardiovascular mortality
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient
Spontaneous myocardial infarction
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient
Admission for heart failure
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient
All-cause mortality or admission for heart failure
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient
Cardiovascular mortality or admission for heart failure
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient
Recurrent non-fatal cardiovascular events (spontaneous myocar-dial infarction and admission for heart failure) with death treated as a terminal event
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient
All-cause mortality in patients with STEMI and type I myocardial infarction
Time Frame: One year after inclusion of the last patient
One year after inclusion of the last patient

Collaborators and Investigators

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

Sponsor

Thomas Engstrom

Collaborators

Odense University Hospital
Aarhus University Hospital
Aalborg University Hospital
Prehospital Center, Region Zealand
Prehospital Emergency Medical Service, The North Denmark Region
Center for Prehospital and Emergency Research, Denmark
Prehospital Emergency Medical Services Central Denmark Region (Præhospitalet)

Investigators

  • Study Director: Thomas Engstrøm, MD, PhD, DMSc, Rigshospitalet, Denmark

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

Helpful Links

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)

April 20, 2026

Primary Completion (Estimated)

April 20, 2031

Study Completion (Estimated)

April 1, 2036

Study Registration Dates

First Submitted

March 10, 2026

First Submitted That Met QC Criteria

March 13, 2026

First Posted (Actual)

March 17, 2026

Study Record Updates

Last Update Posted (Actual)

April 23, 2026

Last Update Submitted That Met QC Criteria

April 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-524320-21-00

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.

Clinical Trials on STEMI - ST Elevation Myocardial Infarction

Clinical Trials on NaCl (0,9%)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe