Prospective Clinical Trial to Investigate Adverse Reactions to MR and CT-examinations (Enhanced and Unenhanced)

Rationale and objectives:

Contrast agents continue to cause concern among patients and doctors because of their widespread use and the rare but potentially important adverse reactions associated with them. Intravenous (into a vein) contrast agents are used daily for both Computed Tomography (CT) and Magnetic Resonance (MR) examinations as an aid for detection and characterization of diseases. Despite their use for millions of examinations each year, the contrast agents are not entirely free of serious and potentially life-threatening adverse reactions. Therefore, the application of both iodine-containing and gadolinium-based contrast agents, respectively for CT and MR- examinations has raised some safety concerns, especially in patients in certain risk groups, e.g. patients with previous allergic reactions to gadolinium and iodine-containing contrast agents, patients with pre-existing renal impairment and diabetes patients. Adverse reactions of contrast agents can be divided into non-renal and renal adverse reactions. The non-renal adverse reactions may be acute or delayed. The acute adverse reactions occur within one hour after the contrast agent is administered to the patient, while the delayed adverse reactions occur after one hour and within a week.Some reactions such as Nephrogenic Systemic Fibrosis (NSF) may occur even later and is classified as a very late adverse reaction. Patients at high risk group should be identified before contrast agent administration to avoid these adverse reactions. Adverse reactions using iodine-containing contrast agents have been known for over 20 years. They are mostly mild or moderate skin reactions that occur during the period 1 hour to 7 days after contrast agent administration, and usually disappear within 3-7 days. Nevertheless, serious and life-threatening adverse reactions occur, and one of the most serious effects is Contrast Induced Nephropathy (CIN), which is a renal adverse reaction. CIN refers to a reduction in the renal function induced by contrast agent. This implies a deterioration in renal function (an increase in serum creatinine by more than 25% or 44μmol / L) occurring within three days after intravascular administration of iodine-containing contrast agent. CIN is a well known complication when it comes to radiological studies using iodine-containing contrast agents. The rapid development and frequent use of CT- examination with simultaneous administration of relatively large doses of iodine-containing contrast agents have contributed to a growing number of cases of CIN during recent years. For many years, gadolinium-based contrast agents have been considered as safe, but in 2006 the first reporting of patients who had developed a new rare potentially fatal disease called NSF in the weeks after exposure to gadolinium-based contrast agents began. However, it was not until 2006 that the NSF was linked to gadolinium contrast agents and it was proposed that the free gadolinium from the contrast agent could be a trigger for NSF. NSF is a connective tissue disease which usually manifests itself as a skin disease with swelling in arms and legs, but can also affect internal organs. NSF occurs in combination with chronic kidney disease and has only recently been particularly investigated.

Therefore, it is essential to clarify if these reactions are actually directly related to the application of contrast agents or to MR/CT-examinations. Most major studies conducted on gadolinium-based and iodine-containing contrast agents have been retrospective, and so far no similar large scale study has been performed independently from pharmaceutical companies. Thus, there is a lack of independent studies, which investigate the severity of adverse reactions as well as delayed adverse reactions one month after the patients have been exposed to the contrast agent.The study aim is to investigate the safety profile for respectively iodine-containing and gadolinium-based contrast agents to CT and MR- examinations in a prospective design. A control group examined without the use of contrast agent will be included, so that the study can illuminate reported adverse reactions related to contrast agents and CT/MR-examinations. This applies to renal, non-renal, and late adverse reactions.

This project will ultimately illuminate any significant and life-threatening late effects and therefore, these will be detected earlier, and it will become more likely to treat the patients in good time for these events. The following series of hypotheses will be investigated in this study:

1. Renal as well as non-renal adverse reactions occurring are related to the use of contrast agent in MR-/CT-examination.
2. CIN occurs in patients undergoing a MR-/CT-examination with contrast agent.