|First Submitted Date||May 25, 2010|
|First Posted Date||May 28, 2010|
|Last Update Posted Date||January 28, 2014|
|Start Date||May 2010|
|Primary Completion Date||December 2012 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures
||Renal and non-renal adverse events to enhanced and unenhanced CT and MRI [ Time Frame: before, 3 days and 1 month after enhanced or unenhanced CT and MRI ]|
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT01132339 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Adverse Reactions to MR and CT-examinations (Enhanced and Unenhanced)|
|Official Title||Prospective Clinical Trial to Investigate Adverse Reactions to MR and CT-examinations (Enhanced and Unenhanced)|
Contrast agents are important tools for MR/CT- examinations, when it comes to diagnosing diseases. But despite their frequent use in Denmark, they are not free of serious and potentially fatal adverse reactions. Examples of this are contrast-induced nephropathy (CIN) and nephrogenic systemic fibrosis (NSF). Therefore, it is extremely important to clarify if these adverse reactions are actually directly related to the use of contrast agents or to MR/CT- examinations.
To prospectively assess the incidence of adverse reactions of iodine-containing CT and gadolinium- based MR contrast agents 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 events related to contrast agents and CT/MR- examinations. This project will in the long term mean that, any significant and life-threatening delayed adverse reactions will be discovered earlier and hence it will be more likely to treat the patients in good time for these adverse reactions.
The following series of hypotheses will be investigated in this study:
Approvals are obtained from The Copenhagen County Committee on Biomedical Research Ethics and Danish Data Protection Agency. A total of 1600 patients will be included from Department of Radiology at Herlev Hospital, where all the MR- and CT examinations will be performed. Patients will be divided into four groups (a, b, c and d) with 400 patients in each group. Group a and c (case group) undergo respectively MR and CT examination with contrast agent While group b and d (control group) will undergo respectively MR and CT examination without the use of contrast agent. For each patient the following will be recorded: Risk factors, renal function (eGFR) before and 72 hours after MR/CT- examination as well as the incidence of immediate reactions (within 30 min.). Furthermore, patients have to answer a questionnaire 72 hours and 1 month after MR/CT- examination about the severity and frequency of adverse reactions to contrast media.
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:
Approvals from The Copenhagen County Committee on Biomedical Research Ethics and The Danish Data Protection Agency are obtained. The study will be conducted as a prospective study at Herlev Hospital, Department of Radiology. Patients referred to an MR/CT-examination will be offered participation in the study. Since the patients are referred to a MR-/CT-examination as part of their patient diagnostic evaluation, the distribution into different groups will be without any influence from the study officials.The study includes a total of 1600 patients in a period of approximately 2 years. The patients will be distributed in four groups (a, b, c and d) with 400 patients in each group. Group a and c (case group) undergo respectively MR- and CT- examinations with respectively gadolinium-based contrast agent and iodine-containing contrast agent. Group b and d (control groups) will undergo MR/CT-examination without any use of contrast agent. Informed consent will be obtained from all patients. Data will be collected continuously. For each participating patient the following will be registered: risk factors (patients allergic to gadolinium-based and iodine-containing contrast agents, patients with renal impairment and diabetes), estimated kidney function (eGFR) with a finger stick blood test immediately before and 72 hours after the MR/CT-examination. The blood test is quick, easy and requires no more than a small stick on the side of the finger tip with a finger stick. The blood drop is placed on a test strip and into a renal function meter, whereupon eGFR is read. The test strip will be destroyed immediately after completion of the test/ measurement. To detect the occurrence of acute adverse reactions after administration of contrast agents, the patients are observed for 30 min. Patients in the control groups will also be observed for 30 minutes after start of MR/CT-examination. All patients are supplied with two questionnaires regarding the occurrence of adverse reactions and possible delayed reactions, which they must complete 72 hours and one month after MR/CT-examination. Results from group a will be compared with results from group b, while the results from group c will be compared with results from group d. This study will not be statistically randomized, since it is an observational study. Furthermore, it is necessary to have a major control group.
Adverse reactions, risks and disadvantages:There are no known adverse reactions in this study, when the exclusion criteria are met. Patients will already be referred for an MR/CT- examination, and contrast agents that are already approved by health authorities will be used as tools for MR/CT-examinations. Therefore, this study does not pose a greater risk or inconvenience to the participants. Moreover, there are no adverse reactions associated with the blood tests measurement.
Study officials have no financial ties to private firms or pharmaceutical companies with interest in this study. Since the majority of researches on contrast agents are made by pharmaceutical companies, this project is important and of great interest since it is independent from the pharmaceutical industry. Therefore, the project's conclusions will not be influenced by strategic and economic interests.
This study is unique in the sense that it so far is, the only major prospective study that follows patients one month after completion of MR/CT-examination. The study is primarily intended as a method to clarify the extent of late adverse reactions that may occur after the patient has left the examination room. For precisely these contrast agents, it is advantageous to have a study which provides a comprehensive systematic overview of acute and late adverse reactions, because many severe and life-threatening late adverse reactions occur days and even weeks after the contrast agent administration. We hope that this study will result in an improved documentation of whether the incidences of acute and delayed severe adverse reactions are directly related to the use of contrast agents for MR/CT-examinations. This will increase patient safety because; it will help clarifying whether adverse reactions are related to contrast agents or MR/CT-examination. For the individual participant the benefit of participation in this study means that, in future any significant delayed adverse reaction will be discovered in time. Furthermore, a detection of the presence of mild or/and moderate adverse reactions will lead to, an earlier treatment of these adverse reactions.
|Study Design||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
|Study Population||The population will be selected from Herlev Hospital, Department of Radiology. Patients referred to an MR/CT-examination will be offered participation in this study.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Completion Date||October 2013|
|Primary Completion Date||December 2012 (Final data collection date for primary outcome measure)|
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||Denmark|
|Removed Location Countries|
|Other Study ID Numbers||H-1-2010-011|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Copenhagen University Hospital at Herlev|
|Study Sponsor||Copenhagen University Hospital at Herlev|
|PRS Account||Copenhagen University Hospital at Herlev|
|Verification Date||January 2014|