Adenosine's Effect on STunning Resolution in Acute Myocardial Infarction (A-STAMI)

Adenosine's Effect on STunning Resolution in Acute Myocardial Infarction An Open-label, Single Center Trial

The aim of this study is to evaluate the effect of adenosine on the recovery of myocardial akinesia in ST-elevation myocardial infarction (STEMI). The study is a single-center randomized clinical trial intending to include 90 patients.

The objective of the study is to investigate whether treatment with adenosine hastens recovery of myocardial akinesia and improves cardiac function at 48 hours in patients with STEMI.

Study Overview

• Status: Withdrawn
• Conditions: Myocardial Ischemia
• Intervention / Treatment: Drug: Adenosine

Detailed Description

Primary endpoint (variable):

The resolution of myocardial stunning at 48 hours (StunningRes48h).

The proportion of stunning that has resolved at 48 hours will be calculated according to the formula:

StunningRes48h = (%AkinesiaBaseline - %Akinesia48h) / (%AkinesiaBaseline - %Akinesia30days) where %AkinesiaT is defined as the endocardial length of the akinetic myocardium measured in end-diastole divided by the total endocardial length measured in end-diastole in the 2- and 4-chamber view, at time T (T= 48h or 30 days)

Secondary endpoint(s) (variables):

1. Infarct size at 6 months, as assessed by cardiac magnetic resonance imaging (magnetic resonance imaging).
2. Ejection fraction days 1, 2, 3, 7, 14, 30 and 6 months.
3. Any sustained ventricular tachycardia or fibrillation within 72 hours (safety endpoint; binary)
4. Any high-grade atrioventricular block or sinus arrest within 72 hours (safety endpoint; binary)
5. Implantation of cardiac assist device within 72 hours (binary)
6. Stroke within 6 months (binary)
7. All-cause mortality within 6 months
8. Heart failure rehospitalization within 6 months*
9. Worsening in-hospital heart failure ≥12 hours after PCI#

10. Composite of any worsening in-hospital heart failure ≥12 hours after PCI or heart failure rehospitalization within 6 months.

    • Defined as re-admission to hospital after discharge, with a total length of admission ≥24 hours, documented worsening of heart failure signs or symptoms (e.g. worsening dyspnea, fatigue, edema/fluid overload, pulmonary venous distension or signs of pulmonary edema on X-ray), with administration of intravenous diuretic or inotropic drugs, ultrafiltration, non-invasive ventilation or mechanical assist device.

      • Defined as intensification of heart failure therapy due to worsening heart failure signs or symptoms (as above; including intravenous diuretic, inotropic or vasopressor drugs, non-invasive ventilation or mechanical assist device).

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years.
2. Anterior STEMI.
3. Symptom duration ≤6 hours

4. Written informed consent obtained - Angiographic Inclusion criteria:

   1. Culprit lesion in LAD, major branch of LAD, proximal or mid LCx or proximal or mid RCA

   2. TIMI flow ≤2 in the culprit vessel

      -Echocardiographic inclusion criteria:

   3. Detectable hypo- or akinesia corresponding to ≥5% of the left ventricle corresponding to culprit lesion, per bedside visual assessment.

Exclusion Criteria:

1. Previous randomization in the study

2. Any of the following contraindications for treatment with adenosine:

   1. Known pre-existing atrioventricular block grade ≥2 or sick sinus syndrome in patients without pacemaker.
   2. Known pre-existing elevation of intracranial pressure
   3. Treatment with dipyridamole within 24 hours of randomization
   4. Systolic blood pressure <80 mm Hg at screening
3. Any concomitant condition resulting in a life expectancy of less than one month
4. Previous myocardial infarction or other cardiac condition resulting in impaired regional or global systolic function without documented recovery of cardiac function
5. Heart transplant or left ventricular assist device recipient
6. Not suitable in the opinion of the investigator due to severe or terminal comorbidity with poor prognosis or characteristics that may interfere with adherence to the trial protocol
7. Pregnancy or woman of childbearing potential who is not sterilized or using a medically accepted form of contraception -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adenosine; Adenosine infusion 70 µg/kg/min initiated prior to revascularization and maintained for 6 hours	Drug: Adenosine; Adenosine infusion 70 µg/kg/min for 6 hours
No Intervention: Controll; Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The resolution of myocardial stunning at 48 hours (StunningRes48h).	The proportion of stunning that has resolved at 48 hours will be calculated according to the formula: StunningRes48h = (%AkinesiaBaseline - %Akinesia48h) / (%AkinesiaBaseline - %Akinesia30days) where %AkinesiaT is defined as the endocardial length of the akinetic myocardium measured in end-diastole divided by the total endocardial length measured in end-diastole in the 2- and 4-chamber view, at time T (T= 48h or 30 days)	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct size	Infarct size, assessed by cardiac magnetic resonance imaging	6 months
Ejection fraction	Ejection fraction, assessed by echocardiography	Day 1, Day 2, Day 3, Day 7, Day 14, Day 30 and 6 months
Sustained ventricular tachycardia or fibrillation	Any sustained ventricular tachycardia or fibrillation within 72 hours	72 hours
High-grade atrioventricular block or sinus arrest	Any high-grade atrioventricular block or sinus arrest within 72 hours	72 hours
Cardiac assist device	Implantation of cardiac assist device within 72 hours	72 hours
Stroke	Stroke within 6 months	6 months
Mortality	All-cause mortality within 6 months	6 months
Rehospitalization	Heart failure rehospitalization within 6 months	6 months
Worsening heart failure	Worsening in-hospital heart failure after PCI	≥12 hours
Composite	Composite of any worsening in-hospital heart failure ≥12 hours after PCI or heart failure rehospitalization within 6 months	≥12 hours or 6 months

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Investigators: Principal Investigator: Björn Redfors, MD, PhD, Vastra Gotaland Region

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: August 12, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Myocardial Ischemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: EudraCT number: 2021-001466-37

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No