Randomised Controlled Trial Evaluating Prophylactic Intravenous Hydration for the Prevention of Contrast Induced Nephropathy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 660
- 试验地点
- 2
- 主要终点
- Cost-Effectiveness of prophylactic intravenous hydration
研究概览
简要总结
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.
详细描述
Studies evaluating the effect of various prophylactic treatments invariably focus on CIN instead of clinically relevant measures as primary outcome. CIN itself being asymptomatic, it is important to determine whether prophylactic treatment has a preventive effect on clinically relevant endpoints sometimes associated with CIN, such as dialysis and mortality. Consider for example: even if it transpires that prophylactic treatment reduces CIN incidence, it may be that intravenous hydration merely dilutes serum creatinine to such an extent that it masks CIN, having no protective effect on renal function. It has been shown that changes in volume status can influence serum creatinine levels, but a potential dilution effect of intravenous hydration has not been investigated to date.
On the other hand, it is important to realise that prophylactic intravenous hydration is not without risk. Patients may suffer mild to serious complications ranging from phlebitis to pulmonary oedema, the latter being potentially fatal. Those patients selected according to the guidelines for the risk of CIN - risk factors including poor renal function, age, diabetes and cardiac disease - are especially sensitive to complications of intravenous hydration. The risk of intravenous hydration in this population has not as yet been charted, and is not taken into account by guidelines for the prevention of CIN.
It stands to reason that a patient's pre-existing hydration status may be a determining factor for the net effect of intravenous hydration: from the same treatment dehydrated patients may enjoy benefits, whereas overhydrated patients may suffer complications. The importance of hydration status in determining the effects of prophylactic hydration, however, has not been investigated to date.
The mechanism by which prophylactic hydration may protect renal function from injury by iodinated contrast material is unclear, as the mechanism by which iodinated contrast material may induce CIN is unclear. Indeed, in patients with chronic renal insufficiency biological variation of serum creatinine in the absence of contrast material has been shown to be indistinguishable from CIN. The question has arisen in recent literature whether CIN is anything more than an asymptomatic increase in serum creatinine, lacking any prognostic negative impact, and not significantly different from that observed in controls not receiving iodinated contrast material.
Recent studies comparing patients with chronic renal deficiency receiving intravascular iodinated contrast material to those patients not receiving iodinated contrast material found no association between increase in serum creatinine (CIN) and contrast administration. Indeed, it has been suggested that renal damage after intra-arterial procedures is caused, not by contrast material, but by cholesterol embolism arising from the erosion of aortic atheromatous plaques by the catheter used in such procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Cost-Effectiveness of prophylactic intravenous hydration
时间窗: 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.
次要结局
- II. Serum creatinine values(26-35 days)
- I. CIN incidence(2-6 days)
- IV. Number of patients in whom cholesterol embolism occurs(9-15 days)
- V. Dose response relationship between contrast material dose and adverse effects(26-35 days & 1 year)
- VI. Kidney function and damage(26-35 days)
- III. Hydration status of patients(26-35 days)
- VII. Number of patients requiring dialysis and mortality(1 year)
研究者
Joachim Wildberger
Pof. Dr. J.E.Wildberger
Maastricht University Medical Center