A Maastricht Contrast-Induced Nephropathy Guidelines Study: CIN Prevention Guidelines: Appropriate & Cost-effective? (AMACING)
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|ClinicalTrials.gov Identifier: NCT02106234|
Recruitment Status : Completed
First Posted : April 8, 2014
Last Update Posted : October 6, 2017
Contrast-induced nephropathy (CIN) is a side-effect of intravascular administration of iodinated contrast material. It is defined as an absolute (>44μmol/l) or relative (>25%) increase in serum creatinine from baseline values within 48-72 hours of iodinated contrast material administration, and usually resolves within two weeks. In some cases CIN has been associated with persistent renal failure, increased risk of dialysis, and mortality. It is not clear however, whether CIN is causally related to this increased risk or whether risk of morbidity and mortality is inherent in those at risk of CIN.
CIN itself is asymptomatic and no treatment for CIN exists. Therefore, the focus lies on its prevention. Prevention guidelines have been drawn up in most countries and been implemented in most radiological departments. In the Netherlands, currently two guidelines for the prevention of CIN coexist, issued by CBO (Centraal BegeleidingsOrgaan) and VMS (Veiligheids Management Systeem).
The prevention guidelines aim to increase patient safety by identifying patients that may be at risk of CIN (mostly patients with chronic renal insufficiency), and subsequently administering prophylactic intravenous hydration to the so identified patients, in order to prevent CIN (intravenous normal saline 4-12 hours before and 4-12 hours after exposure to iodinated contrast material).
Needless to say, the introduction of these guidelines has had a great impact on patient- and health care burden. In the Netherlands alone it is estimated that yearly 100.000 to 150.000 patients receive the prophylactic treatment, incurring a total cost of over 50 million Euro. Considering the steady yearly increase of contrast procedures and the ageing population, it is evident that, in future, these numbers shall only increase further.
The prophylactic treatment prescribed by the guidelines is based on a consensus of the opinion of experts in general agreement that the treatment is beneficial. However, the effectiveness of prophylactic hydration has never been adequately evaluated. Sufficiently large randomised trials comparing prophylactic intravenous hydration with a proper control group receiving no prophylactic treatment are not available, and baseline CIN incidences in untreated populations are unknown. Thus, it is not clear whether prophylactic hydration achieves its aim to prevent CIN.
In order to be able to take effective measures to the benefit of patient safety, it is important to distinguish between the mechanisms underlying CIN and the ensuing increased risk of morbidity and mortality: whether it be biological variation of serum creatinine, renal damage, or cholesterol embolism; whether any causality exists between these and iodinated contrast material; and whether prophylactic intravenous hydration can prevent these from occurring without incurring more risks than it removes. These, in short, are the aims of the AMACING study.
|Condition or disease||Intervention/treatment||Phase|
|Contrast Induced Nephropathy Acute Kidney Injury||Other: No prophylactic iv hydration||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||660 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomised Controlled Trial Evaluating Prophylactic Intravenous Hydration for the Prevention of Contrast Induced Nephropathy|
|Study Start Date :||April 2014|
|Actual Primary Completion Date :||July 2016|
|Actual Study Completion Date :||August 2017|
Active Comparator: Control: NO prophylactic iv hydration
Patients having been referred for an elective procedure involving intravascular iodinated contrast material administration and for intravenous prophylactic hydration according to current guidelines (but only those patients with an eGFR ≥30ml/min/1.73m2) will NOT receive the standard intravenous prophylactic hydration treatment with normal saline prescribed.
Other: No prophylactic iv hydration
Control group: Patients having been referred for an elective procedure involving intravascular iodinated contrast material administration and for intravenous prophylactic hydration according to current guidelines (but only those patients with an eGFR ≥30ml/min/1.73m2) will NOT receive the standard intravenous prophylactic hydration treatment with normal saline prescribed.
No Intervention: Standard care: prophylactic iv hydration
Standard care group:
Patients having been referred for an elective procedure involving intravascular iodinated contrast material administration and for intravenous prophylactic hydration according to current guidelines (but only those patients with an eGFR ≥30ml/min/1.73m2) will receive the standard intravenous prophylactic hydration treatment with normal saline as prescribed.
- Cost-Effectiveness of prophylactic intravenous hydration [ Time Frame: 28-32 days ]
The aim of the guidelines is to prevent CIN. Therefore, even though clinically relevant outcomes would be a preferable primary outcome measure, an evaluation of the cost-effectiveness of the prophylactic treatment prescribed by these guidelines must have costs and CIN incidence as primary outcome measure. The costs per CIN case prevented will be calculated based on the absolute difference in CIN incidence between the randomized groups with and without prophylactic intravenous hydration (non-inferiority randomized trial).
In addition, we will evaluate the performance of prophylactic intravenous hydration in the prevention of clinically relevant effects: decrease in renal function, renal damage and 30-day morbidity/mortality. In the evaluation, we shall take complications of prophylactic intravenous hydration into account. Finally, we will record and evaluate 1 year post-contrast procedure dialysis and mortality of participants.
- I. CIN incidence [ Time Frame: 2-6 days ]CIN incidence using guideline-prescribed baseline values of serum creatinine (which may be up to 12 months old), and using true baseline serum creatinine values (measured on the day of contrast material administration and before start of the treatment) in order to determine difference in CIN incidence between ivhydrated and non-hydrated arms of the RCT; and in order to determine the contribution of biological variation in serum creatinine to CIN incidence recorded in clinical practice.
- II. Serum creatinine values [ Time Frame: 26-35 days ]Prophylactic hydration & its dilution effect on serum creatinine - serum creatinine at baseline, after pre-hydration if applicable, after post-hydration if applicable or contrast procedure, at follow-up time-points 2-5, 10-14 and 28-32 days. Description of changes in serum creatinine during the course of the treatment and comparison between the ivhydrated and non-hydrated arms of the RCT.
- III. Hydration status of patients [ Time Frame: 26-35 days ]Prophylactic hydration: hydration status - Relationship between hydration status of patients (baseline, after pre-hydration if applicable, after post-hydration if applicable or after contrast procedure, and at follow-up time-points) and CIN incidence, renal function, renal damage, adverse events, and 30-day morbidity/mortality.
- IV. Number of patients in whom cholesterol embolism occurs [ Time Frame: 9-15 days ]Serum and urine lactate-dehydrogenase (LDH) values and eosinophil counts in patients with and without CIN; in order to determine the contribution of cholesterol embolism to CIN incidence recorded in clinical practice; comparison between ivhydrated and non hydrated arms of the RCT.
- V. Dose response relationship between contrast material dose and adverse effects [ Time Frame: 26-35 days & 1 year ]Dose-response curves between iodinated contrast material load (iodine load) and CIN, renal function, renal damage, adverse events, 30-day and 1-year morbidity and mortality. Comparsion between ivhydrated and non hydrated arms of the RCT.
- VI. Kidney function and damage [ Time Frame: 26-35 days ]Protective effect of prophylactic hydration: changes in renal function and occurrence of renal damage (using various biomarkers) during the course of the treatment. Difference between the two arms of the RCT.
- VII. Number of patients requiring dialysis and mortality [ Time Frame: 1 year ]1-year renal morbidity & mortality - All the above analyses will be offset against the 1-year dialysis (including frequency and duration), and mortality rates (including probable cause).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02106234
|Maastricht University Medical Center|
|Maastricht, Zuid-Limburg, Netherlands, 6202AZ|
|Principal Investigator:||Joachim E Wildberger, Prof, Dr||Maastricht University Medical Center|