Hyperemic mYocardial Perfusion by adEnosine at diffeRent Doses (HYPER)

Adenosine is a commonly used pharmaceutical stressor at cardiac magnetic resonance examinations to assess suspected chronic coronary syndrome (CCS). However, several studies have reported that the current use of adenosine does not induce adequate hyperemic response in a substantial number of patients, leading to false diagnostics. The aim of this trial is to investigate the hyperemic effect of the standard dose of adenosine (140 microgram/kg/min) to the high dose of adenosine (210 microgram/kg/min) to improve the diagnostic methods using adenosine as a stressor and ultimately improve treatment decisions and patient prognosis in CCS.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Ischemic Heart Disease; Chronic Coronary Syndrome
• Intervention / Treatment: Drug: Adenosine

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Henrik Engblom, MD, PhD; Phone Number: 046171000; Email: henrik.engblom@med.lu.se

Study Locations

• Sweden
  • Lund, Sweden
    • Recruiting
    • Clinical Physiology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital
    • Contact: Henrik Engblom, Professor, MD; Phone Number: 046171000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Patients:

1. The subject has given their written consent to participate in the trial.
2. Are referred to Department of Clinical Physiology, Skåne University Hospital, for suspected or known CCS or heart failure
3. Matches the inclusion criteria for sex and age (6 females and 6 males from each group in each age decade from 40 to >80 years old)
4. Matches the inclusion criteria for no known heart failure (group b) or known heart failure (group c)
5. No caffein intake <24h prior to the examination

Healthy volunteers:

1. The subject has given their written consent to participate in the trial.
2. Matches the inclusion criteria for sex and age (6 females and 6 males from each group in each age decade from 40 to >80 years old)
3. No caffein intake <24h prior to the examination

Exclusion Criteria:

Patients:

1. Acute referral (in-house patients)
2. Clinically unstable
3. Acute chest pain
4. Severe or decompensated heart failure
5. Non sinus rhythm (e.g. atrial fibrillation)
6. Asthma or severe chronic obstructive pulmonary disease
7. Known chronic renal failure (eGFR <45mL/min/1.73m2)
8. AV-block II or III
9. Left Bundle Branch Block
10. Systolic blood pressure <90 mmHg or >230 mmHg at rest
11. Increased intracranial pressure
12. Known allergy or adverse reaction to adenosine or mannitol
13. Known allergy or adverse reaction to gadolinium contrast agents
14. Treatment with medication containing dipyradimol or teofyllamin/teofyllin
15. Claustrophobia
16. Devices contraindicated to CMR imaging (pacemaker, implants, intracranial clips etc)
17. Pregnancy or breast feeding (screened by question only)
18. Inability to give informed consent due to mental state, language difficulties etc

Healthy volunteers:

1. Any of the exclusion criteria for patients
2. Blood pressure > 140/90 measured according to clinical routine
3. Known systemic disease
4. Known cardiac disease
5. Cardiovascular medication
6. Medication that might influence cardiovascular health
7. Smoking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Start standard dose adenosine followed by high dose adenosine; Subjects randomized to this arm will undergo the first stress perfusion acquisition with a dose of 140 μg/kg/min adenosine, followed by a second stress perfusion acquisition with the dose of 210 μg/kg/min adenosine.	Drug: Adenosine; Standard dose 140 μg/kg/min and high dose 210 μg/kg/min adenosine
Active Comparator: Start high dose adenosine followed by standard dose adenosine; Subjects randomized to this arm will undergo the first stress perfusion acquisition with a dose of 210 μg/kg/min adenosine, followed by a second stress perfusion acquisition with the dose of 140 μg/kg/min adenosine.	Drug: Adenosine; Standard dose 140 μg/kg/min and high dose 210 μg/kg/min adenosine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial hyperemia	The primary outcome measure is assessed by quantitative myocardial perfusion CMR imaging (ml/min/g).	During adenosine infusion, 4-6 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate response	Compare heart rate (beat/min) at standard and high dose adenosine	During adenosine infusion, 4-6 minutes
Blood pressure response	Compare systolic blood pressure (mmHg) at standard and high dose adenosine	During adenosine infusion, 4-6 minutes
Symptoms	Compare presence of symptoms (evaluated using a Borg10-scale) at standard and high dose adenosine	During adenosine infusion, 4-6 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex	The association between sex (female and male) and adenosine response	In questionnaire obtained approximately 30 minutes before CMR examination
Age	The association between age (years) and adenosine response	In questionnaire obtained approximately 30 minutes before CMR examination
Ejection fraction	The association between ejection fraction (%) assessed from CMR images and adenosine response	Measured in the obtained short-axis cine images within approximately 6 months after acquisition
Serum-caffeine	The association between serum caffeine levels (mg/L) assessed from blood samples and adenosine response	Blood samples are analysed within 9 months

Collaborators and Investigators

• Sponsor: Region Skane

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 27, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2026
• Last Update Submitted That Met QC Criteria: August 12, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Adenosine; Cardiac Magnetic Resonance; Myocardial perfusion
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Nucleosides; Ribonucleosides; Purine Nucleosides; Adenosine
• Other Study ID Numbers: 2023-505248-20-00

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