Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
ST-segment myocardial infarction
To determine whether 250 mg methylprednisolone administrated in the pre-hospital setting reduces final infarct size on cardiac magnetic resonance (CMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)
Key facts
- Sponsor
- Rigshospitalet, Rigshospitalet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 14 Nov 2022 → ongoing
- Decision date (initial)
- 2022-07-08
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To determine whether 250 mg methylprednisolone administrated in the pre-hospital setting reduces final infarct size on cardiac magnetic resonance (CMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)
Secondary objectives 9
- To determine whether the response of methylprednisolone differs in pre-specified sub-groups: age, gender, pre-percutaneous coronary intervention (PCI), Thrombolysis in Myocardial Infarction (TIMI) flow, culprit in left anterior descending artery (LAD), time from first medical contact to primary PCI, and duration of symptoms prior to primary PCI.
- To determine whether methylprednisolone improves left ventricular ejection fraction (LVEF) within 48 hours and 3 months after primary percutaneous coronary intervention (PCI).
- To determine whether methylprednisolone decreases acute infarct size and edema measured on cardiac magnetic resonance (CMR) within 48 hours of primary PCI.
- To determine whether methylprednisolone decreases the degree of microvascular obstruction (MVO) and hemorrhage measured on cardiac magnetic resonance (CMR) within 48 hours of primary percutaneous coronary intervention (PCI).
- To determine whether methylprednisolone increases myocardial salvage index (MSI) on cardiac magnetic resonance (CMR)
- To determine whether methylprednisolone inhibits the inflammatory response at admission and 24 hours after admission. Markers of inflammation: High sensitivity C-reactive protein (hsCRP), leucocyte- and differential count, plasma cytokine levels (IL-1b, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, G-CSF, GM-CSF, MCP-1, MIP-1beta, INF-g and tumor-necrosis factor α (TNF-α)), and procalcitonin
- To determine whether methylprednisolone increases coronary flow reserve (CFR) and decreases index of microcirculatory resistance (IMR).
- To determine whether methylprednisolone improves clinical outcomes (all-cause mortality and hospitalization for heart failure (HF)) at one year after primary percutaneous coronary intervention (PCI).
- To determine whether methylprednisolone decreases peak Troponin-T and creatine kinase myocardial band (CKMB) during admission.
Conditions and MedDRA coding
ST-segment myocardial infarction
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | PULSE-MI This study is an investigator-initiated, 1:1 randomized, double-blinded, placebo-controlled prospective clinical proof-of-concept trial. The trial will be chaired at the Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark. The study design is described thorough in the protocol section 6.1.
|
Randomised Controlled | Double | [{"id":35221,"code":2,"name":"Investigator"},{"id":35225,"code":1,"name":"Subject"},{"id":35223,"code":4,"name":"Analyst"},{"id":35224,"code":5,"name":"Carer"},{"id":35222,"code":3,"name":"Monitor"}] | Placebo: Intravenous infusion of 4 mL isotonic NaCl (0.9%) over a period of 5 minutes 250 mg methylprednisolone: 2 x 125 mg/2 mL Solu-Medrol, a total of 250 mg/4 mL, which comes as a sterile powder with pre-servative free isotonic NaCl as diluent. The drug is infused over a period of 5 minutes. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Age ≥18 years including fertile women
- Acute onset of chest pain with < 12 hours duration
- ST-segment elevation myocardial infarction (STEMI) characterized as 2 mm ST elevation in 2 or more V1 through V4 leads, or presumed new left bundle branch block with a minimum of 1 mm concordant ST elevation, or 1 mV ST elevation in the limb lead (II, III, and aVF, I, aVL) and V4-V6, or ST depression in 2 or more V1 through V4 leads indicating posterior acute myocardial infarction (AMI)
Exclusion criteria 6
- Presentation with cardiac arrest (out of hospital cardiac arrest (OHCA)
- Time from symptoms onset to primary percutaneous coronary intervention (PCI) > 12 hours
- Known allergy to glucocorticoid or known mental illness with maniac or psychotic episodes
- Previous acute myocardial infarction (AMI) in assumed culprit artery
- Previous coronary artery bypass graft (CABG)
- Unable to read and understand Danish
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Final infarct size (% of left ventricle mass) measured on late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) 3 months following index event.
Secondary endpoints 6
- The extent of microvascular obstruction (MVO) on cardiac magnetic resonance (CMR)
- The extent of hemorrhage on cardiac magnetic resonance (CMR)
- Other cardiac magnetic resonance (CMR) efficacy parameters as specified in appendix A
- All-cause mortality and hospitalization for heart failure at 3 months
- Peak Troponin-T and creatine kinase myocardial band (CKMB)
- Safety: Incidence of adverse events the first seven days of the index event
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD1968077 · Product
- Active substance
- Methylprednisolone
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 250 mg milligram(s)
- Max total dose
- 250 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB04 — METHYLPREDNISOLONE
- Marketing authorisation
- 41159/10/15-2-2012
- MA holder
- PFIZER HELLAS, A.E.
- MA country
- Greece
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Natriumklorid Fresenius Kabi 9 mg/ml infusionsvätska, lösning
PRD2128223 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 4 ml millilitre(s)
- Max total dose
- 4 ml millilitre(s)
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- B05BB01 — ELECTROLYTES
- Marketing authorisation
- 5321
- MA holder
- FRESENIUS KABI AB
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Rigshospitalet
- Sponsor organisation
- Rigshospitalet
- Address
- Blegdamsvej 9
- City
- Copenhagen Ø
- Postcode
- 2100
- Country
- Denmark
Scientific contact point
- Organisation
- Rigshospitalet
- Contact name
- Thomas Engstrøm
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Thomas Engstrøm
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring, Code 9 |
Rigshospitalet
- Sponsor organisation
- Rigshospitalet
- Address
- Blegdamsvej 9
- City
- Copenhagen Ø
- Postcode
- 2100
- Country
- Denmark
Scientific contact point
- Organisation
- Rigshospitalet
- Contact name
- Thomas Engstrøm
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Thomas Engstrøm
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring, Code 9 |
Locations
0 EU/EEA countries · 0 investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2022-11-14 | 2024-10-17 | 2022-11-16 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Pulse Glucocorticoid Therapy In Patients With ST-Segment Elevation Myocardial Infarction SUM-53640
|
2024-10-24T08:48:33 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Lay person summary | 2024-11-19T15:57:49 | Submitted | Laypersons Summary of Results |
Documents 2 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | PULSE-MI CTIS | 1 |
| Summary of results (for publication) | Madsen et al aug 2024 | 1 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-05-05 | Denmark | Acceptable 2022-07-01
|
2022-07-08 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2022-09-21 | Denmark | Acceptable 2022-10-10
|
2022-10-11 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2022-12-22 | Denmark | Acceptable 2023-02-23
|
2023-02-24 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2023-03-08 | Denmark | Acceptable 2023-04-14
|
2023-04-14 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2023-12-07 | Acceptable 2023-04-14
|