A Study of Gadodiamide Injection in Myocardial Perfusion Magnetic Resonance Imaging

A Multicenter, Phase III, Open-label Study of Gadodiamide Injection in Myocardial Perfusion Magnetic Resonance Imaging

The purpose of this study is to determine how well perfusion cardiac magnetic resonance (MR) imaging is able to detect certain heart abnormalities, such as a coronary artery narrowing.

To this purpose, a conventional MR contrast medium (Gd-DTPA-BMA) will be used during an adenosine infusion (an approved substance which enlarges the arteries of the heart, so that the blood flow to the heart muscle increases). This magnetic resonance imaging technique will be compared with single photon emission computed tomography (SPECT), a well-established technique to detect this heart abnormalities.

Both, cardiac MR and SPECT will be compared with invasive coronary angiography, a technique which directly visualized the heart vessels and narrowings of these (=standard of reference).

This study is a multicentre, open label, phase III study in adult subjects designed to show that Gd-DTPA-BMA (a conventional MR contrast medium = OMNISCAN) enhanced myocardial MR perfusion imaging is non-inferior to myocardial SPECT. Both imaging techniques will be performed during adenosine stress (0.14mg/min/kg over 3 minutes IV). Gd-DTPA-BMA will be used twice (2 doses of 0.075 mmol/kg for the stress and rest study each) for the detection of myocardial perfusion defects. The standard of reference is invasive coronary angiography, which defines the presence of coronary artery disease, if vessels of at least 2mm in diameter show stenosis of at least 50% (diameter reduction). Patients with a history of myocardial infarction(s) are positive for coronary artery disease, even when coronary arteries are not stenosed as evidenced by the coronary angiography performed in the setting of this trial(= assigning patients as positive for coronary artery disease after successful PCI-revascularization of acute infarct(s) in the past).

Inclusion Criteria:

1. The subject is a man or woman and is 18 years of age or older.
2. For women of childbearing potential, the results of a urine or serum human chorionic gonadotropin (beta-HCG) pregnancy test, done at screening (with the result known before investigational product administration), must be negative. Only those women who are surgically sterile (have had a documented bilateral oophorectomy and/or documented hysterectomy) or postmenopausal (cessation of menses for more than 1 year) will be allowed to enrol in the study without a pregnancy test at screening.
3. The subject is conscious and able to comply with study procedures.
4. Written, informed consent is obtained.
5. The subject is suspected, as a results of their clinical signs and symptoms, of having CAD (most subjects will probably be included using these criteria).
6. The subject is referred to a quantitative CXA for known or suspected CAD or has undergone quantitative CXA within 4 weeks prior to MRI without any intervention or change of symptoms since the CXA examination.
7. The subject is referred for a SPECT for a functional evaluation of myocardial perfusion or has undergone SPECT within 4 weeks prior to MRI without any intervention, or change in symptoms, between the 2 examinations (the findings of SPECT will not be taken into account for inclusion purposes).

Exclusion Criteria:

1. The subject is lactating.
2. The subject is pregnant as defined by a urine or serum beta-HCG pregnancy test obtained within the 24 hours before dosing.
3. The subject was previously included in this study.
4. The subject received an investigational product in the 30 days before or will receive one during or in the 30 days after investigational product administration.
5. The subject has known allergies or a contra-indication to the investigational product.
6. The subject presents any clinically active, serious, life-threatening disease, with a life expectancy of less than 1 month.
7. The subject received or is scheduled to receive an MRI contrast medium (other than the investigational product) within 24 hours prior to or in the 24 hours following the investigational product administration.
8. The subject received or is scheduled to receive an X-ray contrast medium within 12 hours prior to or 12 hours following the investigational product administration.
9. The subject received or is scheduled to receive a SPECT radiotracer within 24 hours prior to or 24 hours following the investigational product administration.
10. The subject received or is scheduled to receive a stress examination (other than the MR stress examination in this study) within 24 hours prior to or 24 hours following the investigational product administration.
11. The subject has experienced a myocardial infarction within the last 14 days.
12. The subject has experienced more than 1 previous myocardial infarction.
13. The subject has a bypass graft.
14. The subject has second or third degree atrioventricular block, sick sinus syndrome or a symptomatic bradycardia.
15. The subject suffers from asthma, bronchospasms or obstructive pulmonary disease.
16. The subject has severe hypotension (<90 mm Hg systolic).
17. The subject has unstable angina pectoris.
18. The subject has a decompensated congestive cardiac failure.
19. The subject's ECG shows a prolonged QT interval.
20. The subject has a contra-indication for MRI according to clinical guidelines, local regulations or manufacturer's recommendations.
21. The subject has cardiac arrhythmia considered by the investigator to be of a type or of a sufficient degree to make the subject unsuitable for the study.
22. The subject has consumed coffee, tea, coke, chocolate or other caffeinated beverages in the last 24 hours before the adenosine administration.