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

Primary Purpose

Contrast Induced Nephropathy

Status
Unknown status
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Furosemide and matched saline hydration
isotonic saline solution
Sponsored by
Centro Cardiologico Monzino
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Contrast Induced Nephropathy focused on measuring Contrast induced nephropathy, Furosemide, Percutaneous coronary interventions, Saline hydration

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Centro Cardiologico Monzino- University of MilanRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Furosemide and matched saline hydration by RenalGuard system

Standard IV saline infusion

Outcomes

Primary Outcome Measures

Incidence of CIN

Secondary Outcome Measures

Blood chemistry, major adverse clinical events, safety

Full Information

First Posted
June 11, 2008
Last Updated
October 9, 2009
Sponsor
Centro Cardiologico Monzino
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1. Study Identification

Unique Protocol Identification Number
NCT00702728
Brief Title
Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy (CIN) Prevention
Acronym
MYTHOS
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

2. Study Status

Record Verification Date
June 2008
Overall Recruitment Status
Unknown status
Study Start Date
June 2008 (undefined)
Primary Completion Date
June 2009 (Anticipated)
Study Completion Date
December 2009 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Centro Cardiologico Monzino

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Contrast Induced Nephropathy
Keywords
Contrast induced nephropathy, Furosemide, Percutaneous coronary interventions, Saline hydration

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Furosemide and matched saline hydration by RenalGuard system
Arm Title
2
Arm Type
Active Comparator
Arm Description
Standard IV saline infusion
Intervention Type
Drug
Intervention Name(s)
Furosemide and matched saline hydration
Intervention Description
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
Intervention Name(s)
isotonic saline solution
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of CIN
Time Frame
48-72 hours
Secondary Outcome Measure Information:
Title
Blood chemistry, major adverse clinical events, safety
Time Frame
Hospitalizatiojn period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or non-pregnant female equal or greater than the age of 18 years old. 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. Subject is clinically stable for >24hrs defined as Killip Class 1 Baseline Renal Function eGFR < 60ml/min, by MDRD (Modification of Diet in Renal Disease) calculator. Patient has agreed to all follow-up testing. Exclusion Criteria: Catheterization procedure requiring a direct renal injection of contrast or an injection into the descending aorta proximal to the renal arteries. Requires emergent catheterization or primary percutaneous intervention. 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. Known inability to place a Foley catheter Currently has a known electrolyte imbalance or clinically significant arrhythmias which compromise subject's hemodynamic state. Has received intravenous contrast within 10 days of procedure or has a planned procedure using contrast within 72 hours following the procedure. Has documented respiratory insufficiency as evidenced by an oxygen saturation of < 90% on room air assessed on day of procedure. Currently receiving or expected to receive Mannitol or Lithium therapy 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. Subject has a known hypersensitivity to furosemide. 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. If female, subject is pregnant or breastfeeding. Subject is unable to provide informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antonio L Bartorelli, MD
Phone
39-02-58002
Ext
331
Email
antonio.bartorelli@ccfm.it
First Name & Middle Initial & Last Name or Official Title & Degree
Giancarlo Marenzi, MD
Phone
39-02-58002
Ext
582
Email
giancarlo.marenzi@ccfm.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio L Bartorelli, MD
Organizational Affiliation
University of Milan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro Cardiologico Monzino- University of Milan
City
Milan
ZIP/Postal Code
20138
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio L Bartorelli, MD
Phone
39-02-58002
Ext
331
Email
antonio.bartorelli@ccfm.it
First Name & Middle Initial & Last Name & Degree
Giancarlo Marenzi, MD
Phone
39-02-58002
Ext
582
Email
giancarlo.marenzi@ccfm.it
First Name & Middle Initial & Last Name & Degree
Cristina Ferrari, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
14523141
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.
Results Reference
background
PubMed Identifier
11822926
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.
Results Reference
background
PubMed Identifier
7969280
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.
Results Reference
background
PubMed Identifier
16443418
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.
Results Reference
background
PubMed Identifier
22230154
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.
Results Reference
derived

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

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