Contrast Induced NephropathyPhase 3MYTHOSNCT00702728
Induced Diuresis With Matched Hydration Compared to Standard Hydration for Contrast Induced Nephropathy (CIN) Prevention
A Phase 3 study testing Furosemide and matched saline hydration and isotonic saline solution in people with Contrast Induced Nephropathy, run by Centro Cardiologico Monzino at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Contrast Induced Nephropathy
- What is being tested?
- Furosemide and matched saline hydration and isotonic saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2008to Dec 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Centro Cardiologico Monzino- University of Milan
Milan, 20138
Antonio L Bartorelli, MD, 39-02-58002 ext. 331, antonio.bartorelli@ccfm.it
Giancarlo Marenzi, MD, 39-02-58002 ext. 582, giancarlo.marenzi@ccfm.it
About this study
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
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.
Read the 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
- Being tested
- Furosemide and matched saline hydration, isotonic saline solution
- Keywords
- Contrast induced nephropathy, Furosemide, Percutaneous coronary interventions, Saline hydration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide and matched saline hydrationDrug
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.
isotonic saline solutionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Furosemide and matched saline hydration by RenalGuard system Receives: Drug: Furosemide and matched saline hydration |
| 2 | Active comparator | Standard IV saline infusion Receives: Drug: isotonic saline solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of CIN
Measured: 48-72 hours
Secondary outcomes (1)
Blood chemistry, major adverse clinical events, safety
Measured: Hospitalizatiojn period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2008 (estimated)
- Study startJun 2008
- Primary completionJun 2009 (estimated)
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Contrast Induced NephropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro Cardiologico Monzino
- Sponsor type
- University, hospital or other
- Investigators
- Antonio L Bartorelli, MD, Principal investigator, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00702728
- Sponsor's protocol ID
- R100-CCFM S103/208
- Other IDs
- EUDRACT No: 2008-001200-23
- Acronym
- MYTHOS
- Status last verified
- Jun 2008
- First submitted
- 11 Jun 2008
- Last updated
- 12 Oct 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 14523141Mueller 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.
PubMed 11822926Solomon 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.
PubMed 7969280Marenzi 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.
PubMed 16443418Hashimoto 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.
PubMed 39878152Marenzi 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.
PubMed 22230154
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00702728
- Acronym / sponsor ID
- MYTHOS / R100-CCFM S103/208
- Conditions
- Contrast Induced Nephropathy
- Keywords
- Contrast induced nephropathy, Furosemide, Percutaneous coronary interventions, Saline hydration
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Centro Cardiologico MonzinoUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Jun 2009 (estimated)
- Study completion
- Dec 2009 (estimated)
- First posted
- 20 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Furosemide and matched saline hydrationFurosemide and matched saline hydration by RenalGuard system |
| 2 | Active comparator | Drug: isotonic saline solutionStandard IV saline infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Furosemide and matched saline hydrationSubjects 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. | Drug | 1 |
| isotonic saline solutionSubjects 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. | Drug | 2 |
Primary outcome
Incidence of CIN
Time frame: 48-72 hours
1 secondary outcome
Blood chemistry, major adverse clinical events, safety
Time frame: Hospitalizatiojn period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2009.
- Background: PubMed 14523141Marenzi 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.
- Background: PubMed 11822926Mueller 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.
- Background: PubMed 7969280Solomon 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.
- Background: PubMed 16443418Marenzi 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.
- Derived from this study: PubMed 39878152Hashimoto 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.
- Derived from this study: PubMed 22230154Marenzi 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.
- Click here for more information about RenalGuard SystemLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio L Bartorelli, MD principal investigator
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Furosemide and matched saline hydration and isotonic saline solution in people with Contrast Induced Nephropathy, run by Centro Cardiologico Monzino at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antonio L Bartorelli, MD (39-02-58002 ext. 331, antonio.bartorelli@ccfm.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of CIN (time frame: 48-72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00702728, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2009.