RenalGuard System and Contrast Media

NCT01098032 | Completed Phase 3 Results DMC

• 1 other identifier: NCTCM01
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Chronic Kidney Disease

Keywords

Contrast media; Kidney; Complication

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Rate of Kidney Injury and Major Adverse Events

  7 days

• Changes in the Serum Cystatin C Concentration at 24 and 48 Hours After Contrast Exposure

  7 days

• Changes in the Urine and Serum NGAL Concentration After Contrast Exposure

  7 days

• the Rate of Acute Renal Failure Requiring Dialysis

  1 month

• The Rate of In-hospital Major Adverse Events (i.e. Acute Myocardial Infarction, c) Renal Failure Requiring Dialysis, and d) Acute Pulmonary Edema)

  1 month

Study Arms (2)

Systemic alone therapy group

ACTIVE COMPARATOR

Systemic alone therapy group will be treated by intravenous sodium bicarbonate plus NAC administration. 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. (9) The initial i.v. 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. Additional NAC dose (1.2 g) will be administered i.v. during the procedure.

Drug: Systemic alone therapy

RenalGuard System group

EXPERIMENTAL

Prophylactic controlled hydration with saline (0.9%) plus N-acetylcystein (NAC; 6 g in total). In the RenalGuard group, an initial bolus (priming) of 250 ml will be administered. In case of left ventricular dysfunction (ejection fraction ≤30%) and/or unstable hemodynamic conditions the bolus will be reduced to 150 ml. Following the initial bolus, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow (≥300 ml/h). The hydration will be continued throughout the duration of the procedure and will last 4 hours following the procedure. Additional doses of furosemide are allowed in case of decrease of urine flow \<300 ml/h.

Device: RenalGuard system

Interventions

RenalGuard system DEVICE

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.

RenalGuard System group

Systemic alone therapy DRUG

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)

Also known as: Sodium Bicarbonate and N-acetylcysteine

Systemic alone therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>=18 years
• Chronic kidney disease (estimated glomerular filtration rate \<=30 ml/min/1.72 m2) and/or
• Risk score for contrast nephropathy ≥11 (according to the Mehran score; J Am Coll Cardiol 2004; 44: 1393-1399)

You may not qualify if:

• Pregnancy
• Heart failure (NYHA functional class III-IV)
• Acute pulmonary edema
• Acute myocardial infarction
• Recent (\<=2 days) contrast media exposure
• Patients enrolled in concomitant studies
• Administration of theophylline, dopamine, mannitol and fenoldopam.
• End-stage CKD (patients on chronic dialysis)
• Systemic hypotension (systolic blood pressure \< 100 mg/dl).
• Multiple myeloma

Sponsors & Collaborators

• Clinica Mediterranea: lead

Study Sites (4)

Unversity of Ferrara, Department of Cardiology

Ferrara, Italy

Location

IRCCS Multimedica

Milan, Italy

Location

Unversity School of Medicine of Modena, Deparment of Cardiology

Modena, Italy

Location

Clinica Mediterranea

Naples, 80121, Italy

Location

Related Publications (22)

• Tepel M, Aspelin P, Lameire N. Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation. 2006 Apr 11;113(14):1799-806. doi: 10.1161/CIRCULATIONAHA.105.595090. No abstract available.

  PMID: 16606801 BACKGROUND

• 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. doi: 10.1002/ccd.1093.

  PMID: 11285590 BACKGROUND

• 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. doi: 10.1016/s0002-9343(97)00150-2.

  PMID: 9375704 BACKGROUND

• 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. doi: 10.1038/sj.ki.5000375. No abstract available.

  PMID: 16612402 BACKGROUND

• Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium-induced nephropathy. Kidney Int. 2005 Jul;68(1):14-22. doi: 10.1111/j.1523-1755.2005.00377.x.

  PMID: 15954892 BACKGROUND

• 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. doi: 10.1056/NEJM200007203430304.

  PMID: 10900277 BACKGROUND

• 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. doi: 10.1152/ajprenal.1997.272.3.F292.

  PMID: 9087670 BACKGROUND

• 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. doi: 10.1093/ndt/14.4.923.

  PMID: 10328471 BACKGROUND

• 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. doi: 10.1001/jama.291.19.2328.

  PMID: 15150204 BACKGROUND

• 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. doi: 10.1161/01.CIR.0000146396.19081.73. Epub 2004 Oct 18.

  PMID: 15492300 BACKGROUND

• 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. doi: 10.1161/CIRCULATIONAHA.106.687152. Epub 2007 Feb 19.

  PMID: 17309916 BACKGROUND

• 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. doi: 10.1001/jama.290.17.2284.

  PMID: 14600187 BACKGROUND

• 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.

  PMID: 18402894 BACKGROUND

• 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.

  PMID: 18468994 BACKGROUND

• 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. doi: 10.1016/s0735-1097(98)00574-9.

  PMID: 9973020 BACKGROUND

• 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.

  PMID: 7969280 BACKGROUND

• 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. doi: 10.1016/j.jacc.2004.06.068.

  PMID: 15464318 BACKGROUND

• 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. No abstract available.

  PMID: 11904577 BACKGROUND

• 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. doi: 10.1016/j.ehj.2003.11.016.

  PMID: 14972420 BACKGROUND

• Quintavalle C, Anselmi CV, De Micco F, Roscigno G, Visconti G, Golia B, Focaccio A, Ricciardelli B, Perna E, Papa L, Donnarumma E, Condorelli G, Briguori C. Neutrophil Gelatinase-Associated Lipocalin and Contrast-Induced Acute Kidney Injury. Circ Cardiovasc Interv. 2015 Sep;8(9):e002673. doi: 10.1161/CIRCINTERVENTIONS.115.002673.

  PMID: 26333343 DERIVED

• Briguori C, Visconti G, Focaccio A, Airoldi F, Valgimigli M, Sangiorgi GM, Golia B, Ricciardelli B, Condorelli G; REMEDIAL II Investigators. Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard System in high-risk patients for contrast-induced acute kidney injury. Circulation. 2011 Sep 13;124(11):1260-9. doi: 10.1161/CIRCULATIONAHA.111.030759. Epub 2011 Aug 15.

  PMID: 21844075 DERIVED

• Briguori C, Visconti G, Ricciardelli B, Condorelli G; REMEDIAL II Investigators. Renal insufficiency following contrast media administration trial II (REMEDIAL II): RenalGuard system in high-risk patients for contrast-induced acute kidney injury: rationale and design. EuroIntervention. 2011 Apr;6(9):1117-22, 7. doi: 10.4244/EIJV6I9A194.

  PMID: 21518686 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Sodium Bicarbonate; Acetylcysteine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Carlo Briguori, Principal Investigator
• Organization: Clinica Mediterranea

carlobriguori@clinicamediterranea.it

+390817259

Study Officials

• Carlo Briguori, MD, PhD

  Clinica Mediterranea, Naples,. ITALY

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 1, 2010
• First Posted: April 2, 2010
• Study Start: January 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2011
• Last Updated: March 22, 2022
• Results First Posted: March 10, 2015

Record last verified: 2022-03

Locations

IT (4)