RenalGuard System and Contrast Media

Chronic Kidney Disease Clinical Trial

— REMEDIALII  

Official title:

Renal Insufficiency Following Contrast Media Administration Trial II (Remedial II): The RenalGuard System in High-Risk Patients for Contrast-Induced Acute Kidney Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01098032
• Other study ID #: NCTCM01
• Status: Completed
• Phase: Phase 3
• Start date: January 2009
• Est. completion date: December 2011

Study information

• Verified date: March 2022
• Source: Clinica Mediterranea
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the present study is to assess the role of the RenalGuard System as compared to the optimal strategy (sodium bicarbonate infusion plus N-acetylcysteine (NAC)) in high and very-high risk patients to prevent contrast-induced acute kidney injury contrast induced acute kidney injury (CI-AKI).

Consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, will be randomly assigned to 1) prophylactic administration of sodium bicarbonate plus NAC (Systemic alone therapy group; n > 133) and 2) RenalGuard System treatment (RenalGuard group; n > 133). All enrolled patients must have an estimated glomerular filtration rate <30 ml/min/1.73 m2 and/or a contrast nephropathy risk score ≥11). In all cases iodixanol (an iso-osmolar, non ionic contrast agent) will be administered. The primary end point is an increase of >=0.3 mg/dL in the creatinine concentration 48 hours after the procedure.

This study will give important answers on how to prevent CI-AKI in high and very-high risk patients undergoing contrast media exposure.

Description:

The strategy of volume supplementation by sodium bicarbonate plus N-acetylcysteine (NAC) seems to be the optimal pharmacological approach in preventing contrast induced acute kidney injury (CI-AKI) in patients at medium-to-high risk. Whether this prophylactic strategy is effective in high and very-high risk patients is unknown. In this subset of patients the potential protective effects and therapeutic advantage of a local delivery of protective compounds should be investigated. The RenalGuard™ System (PLC Medical Systes, Inc.) is a real-time measurement and real time matched fluid replacement device designed to accommodate the RenalGuard Therapy. The RenalGuard Therapy is based on the theory that creating and maintaining a high urine output is beneficial to patients undergoing imaging procedures where contrast agents are used. This should allow the body to rapidly eliminate contrast, reducing its toxic effects. The RenalGuard System seems to be ideal for the prevention of CI-AKI, by allowing an optimal urine flow rate >150 ml/h (ideally >300 ml/h). Preliminary data suggests that the RenalGuard System, by increasing the urine flow rate ≥ 300 ml/h, allows a quick renal first-pass elimination and therefore reduces the risk for contrast nephropathy. The potential benefits of RenalGuard Therapy are intended to reduce the incidence of CI-AKI via a combination of known physiological effects of high urine output including: a) lower concentration of contrast in the kidneys, b) more rapid transit of contrast through the kidneys, c) less overall exposure to toxic contrast, d) potential reduction of oxygen consumption in the medulla of the kidneys. No randomized study has been performed to assess the role of the RenalGuard System as compared to the optimal strategy (sodium bicarbonate infusion plus NAC) in high and very-high risk patients to prevent CI-AKI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 294
• Est. completion date: December 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >=18 years

2. Chronic kidney disease (estimated glomerular filtration rate <=30 ml/min/1.72 m2) and/or

3. Risk score for contrast nephropathy =11 (according to the Mehran score; J Am Coll Cardiol 2004; 44: 1393-1399)

Exclusion Criteria:

1. Pregnancy

2. Heart failure (NYHA functional class III-IV)

3. Acute pulmonary edema

4. Acute myocardial infarction

5. Recent (<=2 days) contrast media exposure

6. Patients enrolled in concomitant studies

7. Administration of theophylline, dopamine, mannitol and fenoldopam.

8. End-stage CKD (patients on chronic dialysis)

9. Systemic hypotension (systolic blood pressure < 100 mg/dl).

10. Multiple myeloma

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Device:
• RenalGuard system
The RenalGuard™ System (PLC Medical Systems, Inc.) is a real-time measurement and real time matched fluid replacement device designed to accommodate the RenalGuard Therapy. The RenalGuard Therapy is based on the concept demonstrated by clinical data that high urine output is beneficial to patients with impaired baseline renal function who receive intravascular iodinated contrast medio (CM). The RenalGuard System seems to be ideal for the prevention of CI-AKI, by allowing an optimal urine flow rate >300 ml/h. It is known that excessive diuresis can cause dehydration which increases the risk to the kidneys from CM. The RenalGuard System should allow the patient to achieve high urine output safely by maintaining the intravascular blood volume and avoiding the risk of over-or-under-hydration.

Drug:
• Systemic alone therapy
Patients allocated to the Systemic alone therapy group will receive 154 mEq/l of sodium bicarbonate in dextrose and H2O, according to the protocol reported by Merten et al. The initial intravenous bolus was 3 ml/kg per hour for 1 hour immediately before contrast injection. Following this, patients will receive the same fluid at a rate of 1 ml/kg per hour during contrast exposure and for 6 hours after the procedure. All patients will receive NAC (Fluimucil, Zambon Group SpA, Milan, Italy) orally at a dose of 1200 mg twice daily on the day before and on the day of administration of the contrast agent (total of 2 days)

Locations

Country	Name	City	State
Italy	Unversity of Ferrara, Department of Cardiology	Ferrara
Italy	IRCCS Multimedica	Milan
Italy	Unversity School of Medicine of Modena, Deparment of Cardiology	Modena
Italy	Clinica Mediterranea	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Mediterranea

Country where clinical trial is conducted

Italy, 

References & Publications (19)

Briguori C, Airoldi F, D'Andrea D, Bonizzoni E, Morici N, Focaccio A, Michev I, Montorfano M, Carlino M, Cosgrave J, Ricciardelli B, Colombo A. Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL): a randomized comparison of 3 preventive strategies. Circulation. 2007 Mar 13;115(10):1211-7. Epub 2007 Feb 19. — View Citation

Briguori C, Colombo A, Violante A, Balestrieri P, Manganelli F, Paolo Elia P, Golia B, Lepore S, Riviezzo G, Scarpato P, Focaccio A, Librera M, Bonizzoni E, Ricciardelli B. Standard vs double dose of N-acetylcysteine to prevent contrast agent associated nephrotoxicity. Eur Heart J. 2004 Feb;25(3):206-11. — View Citation

DiMari J, Megyesi J, Udvarhelyi N, Price P, Davis R, Safirstein R. N-acetyl cysteine ameliorates ischemic renal failure. Am J Physiol. 1997 Mar;272(3 Pt 2):F292-8. — View Citation

Gruberg L, Mehran R, Dangas G, Mintz GS, Waksman R, Kent KM, Pichard AD, Satler LF, Wu H, Leon MB. Acute renal failure requiring dialysis after percutaneous coronary interventions. Catheter Cardiovasc Interv. 2001 Apr;52(4):409-16. — View Citation

McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med. 1997 Nov;103(5):368-75. — View Citation

McCullough PA. Contrast-induced acute kidney injury. J Am Coll Cardiol. 2008 Apr 15;51(15):1419-28. doi: 10.1016/j.jacc.2007.12.035. Review. Erratum in: J Am Coll Cardiol.2008 Jun 3;51(22): 2197. — View Citation

Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, Mintz GS, Lansky AJ, Moses JW, Stone GW, Leon MB, Dangas G. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004 Oct 6;44(7):1393-9. — View Citation

Merten GJ, Burgess WP, Gray LV, Holleman JH, Roush TS, Kowalchuk GJ, Bersin RM, Van Moore A, Simonton CA 3rd, Rittase RA, Norton HJ, Kennedy TP. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 May 19;291(19):2328-34. — View Citation

National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. — View Citation

Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium-induced nephropathy. Kidney Int. 2005 Jul;68(1):14-22. Review. — View Citation

Romano G, Briguori C, Quintavalle C, Zanca C, Rivera NV, Colombo A, Condorelli G. Contrast agents and renal cell apoptosis. Eur Heart J. 2008 Oct;29(20):2569-76. doi: 10.1093/eurheartj/ehn197. Epub 2008 May 8. — View Citation

Solomon R, Deray G; Consensus Panel for CIN. How to prevent contrast-induced nephropathy and manage risk patients: practical recommendations. Kidney Int Suppl. 2006 Apr;(100):S51-3. — View 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. — View Citation

Spargias K, Alexopoulos E, Kyrzopoulos S, Iokovis P, Greenwood DC, Manginas A, Voudris V, Pavlides G, Buller CE, Kremastinos D, Cokkinos DV. Ascorbic acid prevents contrast-mediated nephropathy in patients with renal dysfunction undergoing coronary angiography or intervention. Circulation. 2004 Nov 2;110(18):2837-42. Epub 2004 Oct 18. Erratum in: Circulation. 2005 Jan 25;111(3):379. Iacovis, Panagiotis [corrected to Iokovis,Panagiotis]. — View Citation

Stevens MA, McCullough PA, Tobin KJ, Speck JP, Westveer DC, Guido-Allen DA, Timmis GC, O'Neill WW. A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation. J Am Coll Cardiol. 1999 Feb;33(2):403-11. — View Citation

Stone GW, McCullough PA, Tumlin JA, Lepor NE, Madyoon H, Murray P, Wang A, Chu AA, Schaer GL, Stevens M, Wilensky RL, O'Neill WW; CONTRAST Investigators. Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial. JAMA. 2003 Nov 5;290(17):2284-91. — View Citation

Tariq M, Morais C, Sobki S, Al Sulaiman M, Al Khader A. N-acetylcysteine attenuates cyclosporin-induced nephrotoxicity in rats. Nephrol Dial Transplant. 1999 Apr;14(4):923-9. — View Citation

Tepel M, Aspelin P, Lameire N. Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation. 2006 Apr 11;113(14):1799-806. Review. — View Citation

Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000 Jul 20;343(3):180-4. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Contrast-induced Acute Kidney Injury	The primary outcome measure will be the rate of development of CI-AKI in the 2 study arms (number of participants). CI-AKI is defined as an increase in the serum creatinine concentration >=0.3 mg/dL from the baseline value at 48 hours after administration of the contrast media or the need for dialysis.	at 48 hours following contrast exposure
Secondary	Rate of Kidney Injury and Major Adverse Events	an increase in the serum creatinine concentration >=0.25% and >=0.5 mg/dl at 48 hours after contrast exposure	7 days
Secondary	Changes in the Serum Cystatin C Concentration at 24 and 48 Hours After Contrast Exposure	Cystatin C is an alternative biomarker of kidney damage. Cystatin C seems to be superior to serum creatinine an identifying kidney function and damage.	7 days
Secondary	Changes in the Urine and Serum NGAL Concentration After Contrast Exposure	NGAL is a new biomarker which seems to be very promising in detecting kidney injury. prelimiary data suggest that urine and serum NGAL increase very early (within few horurs) after the occurrence og acute kidney damage. Therefore, NGAL may be a real marker of acute kidney injury.	7 days
Secondary	the Rate of Acute Renal Failure Requiring Dialysis	occurrence of renal failure requiring dialysis represents the haard endpoint of the study. Actually this represents the worst clinical consequence of CI-AKI.	1 month
Secondary	The Rate of In-hospital Major Adverse Events (i.e. Acute Myocardial Infarction, c) Renal Failure Requiring Dialysis, and d) Acute Pulmonary Edema)	Assessment of the rate of in-hospital major adverse events (i.e. acute myocardial infarction, c) renal failure requiring dialysis, and d) acute pulmonary edema) will give important informantion on the clinical relevance of prophylactic strategies in preventing CI-AKI	1 month
Secondary	The Cost-effectiveness Ratio.	Assessement of the cost-effectiveness ratio is important when testing a new strategy of both therapy and prophylaxis. The Renalguard system is more expensive than the conventional hydration regimen. The cost of RenalGuard system is approximately 800 $. This cost will be justified only if the system is more effective in preventing CI-AKI and improving the clinical outcome, expecially reducing the lenght of ospedalization and the rate of dialysis.	1 month