Clinical trial NCT00702728: Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy (CIN) Prevention
Official title: A Study to Evaluate the Effectiveness of Induced Diuresis With Matched Hydration Therapy Compared to Standard Overnight Hydration in the Prevention of Contrast Induced Nephropathy -MYTHOS Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Contrast Induced Nephropathy
Keywords: Contrast induced nephropathy
Furosemide
Percutaneous coronary interventions
Saline hydration
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
First posted: 2008-06-20
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is being proposed with the objective to assess the potential benefits of induced diuresis by furosemide with matched hydration therapy compared to standard hydration in the prevention of contrast-induced nephropathy (CIN). It is expected that matched hydration will prove to be as effective as hydration alone, will avoid an overnight stay prior to the procedure, and thus will prove to be a less costly and more clinically manageable solution to the prevention of CIN.

Detailed description: Radiocontrast agents (contrast) are widely used in coronary and peripheral vascular catheterization procedures. Although the use of these iodine-containing agents is vital for these procedures, it can be associated with adverse side effects. CIN is one of the most important adverse effects of contrast agents, and can cause substantial morbidity and mortality.

Although the exact mechanisms remain unknown, intravenous hydration before the catheterization procedure is the only current treatment that has been shown to reduce the incidence of CIN. However, in patients with baseline impairments in renal function, hydration is commonly performed at a rate significantly lower than that shown to provide protection due to the fear of overhydration and pulmonary edema. Previous studies have used diuretics to increase urine output and prevent overhydration. In addition to the benefit of increased urine flow, loop diuretics, such as furosemide, should be expected to provide additive benefit against another potential mechanism of CIN, medullary ischemia, as they reduce sodium reabsorption, and consequentially oxygen consumption, of the kidney. While the results of their use have been mixed, it appears that furosemide was deleterious in patients who became dehydrated, i.e. those in whom the urine output was substantially greater than the rate of hydration they received.

This problem may be overcome by a device, which is now available on the market, called the RenalGuard System. The System is capable of delivering saline solution to a patient in an amount matched to the volume of urine produced by the patient. The purpose of this matched fluid replacement is to prevent hypovolemia that may lead to hypotension or fluid overload.The aim of the study is to compare furosemide-induced diuresis with matched hydration therapy compared to standard hydration.

Eligibility criteria: Inclusion Criteria:

1. Male or non-pregnant female equal or greater than the age of 18 years old.
2. Scheduled to undergo a non-emergent catheterization procedure with anticipated to use ≥80 ml contrast media. Additional other procedure (e.g., left ventriculography, imaging of grafts, stenting, etc.) are allowable other than those listed below as exclusion criteria #1.
3. Subject is clinically stable for \>24hrs defined as Killip Class 1
4. Baseline Renal Function eGFR \< 60ml/min, by MDRD (Modification of Diet in Renal Disease) calculator.
5. Patient has agreed to all follow-up testing.

Exclusion Criteria:

1. Catheterization procedure requiring a direct renal injection of contrast or an injection into the descending aorta proximal to the renal arteries.
2. Requires emergent catheterization or primary percutaneous intervention.
3. Subject is anuric, has been hospitalized for any change in renal function or has undergone renal replacement therapy (hemodialysis or hemofiltration) within the past month.
4. Known inability to place a Foley catheter
5. Currently has a known electrolyte imbalance or clinically significant arrhythmias which compromise subject's hemodynamic state.
6. Has received intravenous contrast within 10 days of procedure or has a planned procedure using contrast within 72 hours following the procedure.
7. Has documented respiratory insufficiency as evidenced by an oxygen saturation of \< 90% on room air assessed on day of procedure.
8. Currently receiving or expected to receive Mannitol or Lithium therapy
9. Planned addition, discontinuation or dose adjustment of the trimethoprim, cimetidine, metaclopramide and/or the use of non-steroidal anti-inflammatory drugs within 48 hours of the procedure.
10. Subject has a known hypersensitivity to furosemide.
11. Subject is currently, plans, or has been enrolled in another clinical study involving use of an investigational drug or device within the prior 30 days.
12. If female, subject is pregnant or breastfeeding.
13. Subject is unable to provide informed consent.

Primary outcomes:
measure: Incidence of CIN
timeFrame: 48-72 hours
Secondary outcomes:
measure: Blood chemistry, major adverse clinical events, safety
timeFrame: Hospitalizatiojn period
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Centro Cardiologico Monzino- University of Milan
Study officials:
affiliation: University of Milan
name: Antonio L Bartorelli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marenzi G, Marana I, Lauri G, Assanelli E, Grazi M, Campodonico J, Trabattoni D, Fabbiocchi F, Montorsi P, Bartorelli AL. The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med. 2003 Oct 2;349(14):1333-40. doi: 10.1056/NEJMoa023204.
citation: Mueller C, Buerkle G, Buettner HJ, Petersen J, Perruchoud AP, Eriksson U, Marsch S, Roskamm H. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med. 2002 Feb 11;162(3):329-36. doi: 10.1001/archinte.162.3.329.
citation: Solomon R, Werner C, Mann D, D'Elia J, Silva P. Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med. 1994 Nov 24;331(21):1416-20. doi: 10.1056/NEJM199411243312104.
citation: Marenzi G, Lauri G, Campodonico J, Marana I, Assanelli E, De Metrio M, Grazi M, Veglia F, Fabbiocchi F, Montorsi P, Bartorelli AL. Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients. Am J Med. 2006 Feb;119(2):155-62. doi: 10.1016/j.amjmed.2005.08.002.
citation: Marenzi G, Ferrari C, Marana I, Assanelli E, De Metrio M, Teruzzi G, Veglia F, Fabbiocchi F, Montorsi P, Bartorelli AL. Prevention of contrast nephropathy by furosemide with matched hydration: the MYTHOS (Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy Prevention) trial. JACC Cardiovasc Interv. 2012 Jan;5(1):90-7. doi: 10.1016/j.jcin.2011.08.017.