A Maastricht Contrast-Induced Nephropathy Guidelines Study: CIN Prevention Guidelines: Appropriate & Cost-effective?

NCT02106234 | Completed DMC

• 1 other identifier: NL47173.068.14
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Contrast Induced Nephropathy; Acute Kidney Injury

Keywords

contrast induced nephropathy; prophylactic intravenous hydration; intravenous normal saline; acute kidney injury

Outcome Measures

Primary Outcomes (1)

• Cost-Effectiveness of prophylactic intravenous hydration

  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.

  28-32 days

Secondary Outcomes (7)

• I. CIN incidence

  2-6 days

• II. Serum creatinine values

  26-35 days

• III. Hydration status of patients

  26-35 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

Study Arms (2)

Control: NO prophylactic iv hydration

ACTIVE COMPARATOR

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.

Other: No prophylactic iv hydration

Standard care: prophylactic iv hydration

NO INTERVENTION

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.

Interventions

No prophylactic iv hydration OTHER

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.

Control: NO prophylactic iv hydration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age
• referred for an elective procedure with intravascular iodinated contrast material administration
• at risk of developing CIN according to the CBO prevention guidelines and referred for prophylactic intravenous hydration. \[the 4 high risk groups according to the guidelines are: 1. Kahler's disease (multiple myeloma) or Waldenström's macroglobulinemia with small chain proteinuria irrespective of eGFR; 2. eGFR \<45 ml/min/1.73m2; 3. eGFR \<60 ml/min/1.73m2 \& diabetes mellitus; 4. eGFR \<60 ml/min/1.73m2 \& ≥2 of the following risk factors: age\>75, anaemia, use of nephrotoxic medication such as diuretics or nonsteroidal anti-inflammatory drugs, cardiac /peripheral vascular disease.\]

You may not qualify if:

• No prophylactic treatment prescribed by referring physician
• Intensive care or emergency patient
• Patient receiving or having received renal replacement therapy
• Patients with severely decreased renal function (i.e. eGFR\<30ml/min/1.73m2)

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Zuid-Limburg, 6202AZ, Netherlands

Location

Related Publications (3)

• Nijssen EC, Rennenberg RJ, Nelemans PJ, Essers BA, Janssen MM, Vermeeren MA, Ommen VV, Wildberger JE. Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial. Lancet. 2017 Apr 1;389(10076):1312-1322. doi: 10.1016/S0140-6736(17)30057-0. Epub 2017 Feb 21.

  PMID: 28233565 RESULT

• Nijssen EC, Nelemans PJ, Rennenberg RJ, van Ommen V, Wildberger JE. Prophylactic Intravenous Hydration to Protect Renal Function From Intravascular Iodinated Contrast Material (AMACING): Long-term Results of a Prospective, Randomised, Controlled Trial. EClinicalMedicine. 2018 Nov 9;4-5:109-116. doi: 10.1016/j.eclinm.2018.10.007. eCollection 2018 Oct-Nov.

  PMID: 31193613 DERIVED

• Nijssen EC, Rennenberg RJ, Nelemans PJ, Essers BA, Janssen MM, Vermeeren MA, van Ommen V, Wildberger JE. [Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial]. Ned Tijdschr Geneeskd. 2018;161:D1734. Dutch.

  PMID: 29328007 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Joachim E Wildberger, Prof, Dr

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pof. Dr. J.E.Wildberger

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: April 8, 2014
• Study Start: April 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: August 1, 2017
• Last Updated: October 6, 2017

Record last verified: 2017-10

Locations

NL (1)