Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy (CIN) Prevention

NCT ID: NCT00702728

Last Updated: 2009-10-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2009-12-31

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.

Conditions

Contrast Induced Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

Furosemide and matched saline hydration by RenalGuard system

Group Type: EXPERIMENTAL

Furosemide and matched saline hydration

Intervention Type: DRUG

Subjects will begin treatment approximately 90 minutes prior to the start of catheterization procedure. After a pre-hydration bolus of 250 ml of normal saline solution over 30 minutes the patient will receive 0.5 mg/kg of furosemide intravenously. Then, a replacement solution (saline) is given in an amount matched (ml for ml) to the volume of urine produced. Matched hydration will occur prior, during, and 4 hours post procedure.

2

Standard IV saline infusion

Group Type: ACTIVE_COMPARATOR

isotonic saline solution

Intervention Type: DRUG

Subjects will receive 1 ml/Kg/hr of intravenous saline solution for a minimum of 12 hours prior to catheterization. Hydration will continue to occur during the catheterization, and for a minimum of 12 hours post catheterization.

Interventions

Furosemide and matched saline hydration

Subjects will begin treatment approximately 90 minutes prior to the start of catheterization procedure. After a pre-hydration bolus of 250 ml of normal saline solution over 30 minutes the patient will receive 0.5 mg/kg of furosemide intravenously. Then, a replacement solution (saline) is given in an amount matched (ml for ml) to the volume of urine produced. Matched hydration will occur prior, during, and 4 hours post procedure.

Intervention Type: DRUG

isotonic saline solution

Subjects will receive 1 ml/Kg/hr of intravenous saline solution for a minimum of 12 hours prior to catheterization. Hydration will continue to occur during the catheterization, and for a minimum of 12 hours post catheterization.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or non-pregnant female equal or greater than the age of 18 years old.

Exclusion Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro Cardiologico Monzino

OTHER

Sponsor Role: lead

Responsible Party

Centro Cardiologico Monzino- University of Milan

Principal Investigators

Antonio L Bartorelli, MD

Role: PRINCIPAL_INVESTIGATOR

University of Milan

Locations

Centro Cardiologico Monzino- University of Milan

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Antonio L Bartorelli, MD

Role: CONTACT

antonio.bartorelli@ccfm.it

39-02-58002 ext. 331

Giancarlo Marenzi, MD

Role: CONTACT

giancarlo.marenzi@ccfm.it

39-02-58002 ext. 582

Facility Contacts

Antonio L Bartorelli, MD

Role: primary

antonio.bartorelli@ccfm.it

39-02-58002 ext. 331

Giancarlo Marenzi, MD

Role: backup

giancarlo.marenzi@ccfm.it

39-02-58002 ext. 582

References

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.

Reference Type: BACKGROUND

PMID: 14523141 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11822926 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7969280 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16443418 (View on PubMed)

Hashimoto H, Yamada H, Murata M, Watanabe N. Diuretics for preventing and treating acute kidney injury. Cochrane Database Syst Rev. 2025 Jan 29;1(1):CD014937. doi: 10.1002/14651858.CD014937.pub2.

Reference Type: DERIVED

PMID: 39878152 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22230154 (View on PubMed)

Other Identifiers

EUDRACT No: 2008-001200-23

Identifier Type: -

Identifier Source: secondary_id

R100-CCFM S103/208

Identifier Type: -

Identifier Source: org_study_id