Renal Insufficiency Following Contrast Media Administration Trial III

NCT02489669 | Unknown DMC

• 1 other identifier: NCT004
• Study Type: interventional
• Target: 700
• Locations: 0 countries
• Sites: N/A

Brief Summary

The urine flow rate (UFR)-guided and the left-ventricular end-diastolic pressure (LVEDP)-guided hydration regimens have been proposed to prevent contrast-induced acute kidney injury (CI-AKI). The REnal Insufficiency Following Contrast MEDIA Administration TriaL III (REMEDIAL III) trial is a randomized, multicenter, investigator-sponsored trial aiming to compare these 2 hydration strategies in high risk patients. Patients with estimated glomerular filtration rate \<45 ml/min/1.73 m2 and/or a high risk for CI-AKI (as defined according to both Mehran's score ≥11 and/or Gurm's score \>7) will be enrolled. Patients will be divided in high (\>12 mm Hg) and normal LVEDP, non-invasively estimated by transmitral flow velocity to annular velocity ratio (E/E' index). Patients in each group will be randomly assigned to 1) LVEDP-guided hydration with normal saline (LVEDP-guided group). The fluid infusion rate will be adjusted according to the LVEDP as follows: 5 mL/kg/hr for LVEDP \<12 mmHg; 3 mL/kg/hr for 13-18 mmHg; and 1.5 mL/kg/hr for \>18 mmHg. 2) UFR-rate guided hydration (RenalGuard group). In this group, hydration with normal saline plus low-dose of furosemide is controlled by the RenalGuard system, in order to reach and maintain a high (\>300 mL/h) UFR. In all cases iobitridol (an low-osmolar, non ionic contrast agent) will be administered. The primary endpoint is the composite of CI-AKI (i.e., serum creatinine increase ≥ 25% and ≥ 0.5 mg/dl from the baseline value at 48 hours after contrast media exposure) and/or acute pulmonary edema.

Conditions

Contrast Nephropathy

Outcome Measures

Primary Outcomes (1)

• Composite of 1) development of CI-AKI, and/or acute pulmonary edema.

  The primary outcome measure is composite of 1) development of CI-AKI, and/or acute pulmonary edema. CI-AKI is defined as an increase in the serum creatinine concentration \>=25% and \>=0.5 mg/dl from the baseline value at 48 hours after administration of the contrast media or the need for dialysis

  within 48 hours after contrast media exposure

Secondary Outcomes (6)

• Creatinine change

  48 hours

• Cystatin C change

  48 hours

• Dialysis rate

  5 days

• Major adverse event rate

  12 months

• Length of in-hospital stay (LOS)

  30 days

Study Arms (2)

LVEDP-guided group

NO INTERVENTION

Patients allocated to the LVEDP-guided group will continue to receive intravenous 0.9% sodium chloride, according to the protocol suggested in the POSEIDON trial (that is, 5 mL/kg/hr for LVEDP ≤12 mmHg; 3 mL/kg/hr for 13-18 mmHg; and 1.5 mL/kg/h for \>18 mmHg). The fluid rate will be eventually modified at the start of the procedure in case of discordance between non-invasive and invasive LVEDP pressure estimate, being the invasive value considered as gold-standard. The fluid rate will continued during the procedure, and for 4 hours post-procedure.

Renalguard group

EXPERIMENTAL

Patients enrolled in this group will be treated by hydration with 0.9% saline controlled by the RenalGuard system. On top of the 1.5-5.0 ml/kg/h that patients would have received over the previous hour (according to the non-invasive estimate LVEDP), an initial bolus of 250 ml will be administered. In case of LV ejection fraction ≤30% and/or LVEDP \>18 mm Hg the bolus will 150 mL. Therefore, furosemide (0.25 mg/kg) will be administered in order to achieve the optimal urine flow rate (≥300 mL/h). The controlled hydration by the RenalGuard system will be continued during the procedure and for 4 hours following the procedure. Urine flow rate is monitored and maintained at the target value through the procedure and during the following 4 hours. Additional furosemide doses are allowed in case of decrease of the urine flow rate below the target value.

Device: RenalGuard system™® (PLC Medical Systems, Inc. Franklin, MA, USA)

Interventions

RenalGuard system™® (PLC Medical Systems, Inc. Franklin, MA, USA) DEVICE

Patients in the RenalGuard group will be treated by hydration with normal saline controlled by the RenalGuard system™® (PLC Medical Systems, Inc. Franklin, MA, USA). The RenalGuard system includes a) a closed loop fluid management system; b) a high volume fluid pump, c) a high accuracy dual weight measuring system; d) motion detection artifact reduction; e) a single use intravenous set and urine collection system that interfaces with a standard Foley catheter; f) real-time display of urine and replacement fluid volume; g) a timely alerts to drain the urine bag or to replace the hydration fluid bag; f) and safety features such as automatic air and occlusion detection.

Renalguard group

Eligibility Criteria

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

You may qualify if:

• All consecutive patients with chronic kidney disease (CKD) scheduled for coronary and/or peripheral angiography and/or angioplasty with an eGFR \<45 ml/min/1.73 m2 and/or
• At high risk for CI-AKI according to Mehran's score ≥11 and/or Gurm's score \>7

You may not qualify if:

• Age \<18 years
• Women who are pregnant
• Acute pulmonary edema
• Acute myocardial infarction
• Recent contrast media exposure
• End-stage CKD on chronic dialysis
• Multiple myeloma
• Current enrolment in any other study when enrolment in the REMEDIAL III would involve deviation from either protocol
• Cardiogenic shock
• Administration of theophilline, dopamine, mannitol and fenoldopam

Sponsors & Collaborators

• Clinica Mediterranea: lead

Related Publications (18)

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  PMID: 18402894 RESULT

• 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 RESULT

• Briguori C, Visconti G, Rivera NV, Focaccio A, Golia B, Giannone R, Castaldo D, De Micco F, Ricciardelli B, Colombo A. Cystatin C and contrast-induced acute kidney injury. Circulation. 2010 May 18;121(19):2117-22. doi: 10.1161/CIRCULATIONAHA.109.919639. Epub 2010 May 3.

  PMID: 20439784 RESULT

• 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 RESULT

• Brar SS, Aharonian V, Mansukhani P, Moore N, Shen AY, Jorgensen M, Dua A, Short L, Kane K. Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial. Lancet. 2014 May 24;383(9931):1814-23. doi: 10.1016/S0140-6736(14)60689-9.

  PMID: 24856027 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• World Medical Association Inc. Declaration of Helsinki. Ethical principles for medical research involving human subjects. J Indian Med Assoc. 2009 Jun;107(6):403-5. No abstract available.

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  PMID: 15969305 RESULT

• Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, Hoffmann W, Poller W, Schultheiss HP, Pauschinger M, Tschope C. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation. 2007 Aug 7;116(6):637-47. doi: 10.1161/CIRCULATIONAHA.106.661983. Epub 2007 Jul 23.

  PMID: 17646587 RESULT

• Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation. 2000 Oct 10;102(15):1788-94. doi: 10.1161/01.cir.102.15.1788.

  PMID: 11023933 RESULT

• How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure. Eur Heart J. 1998 Jul;19(7):990-1003. doi: 10.1053/euhj.1998.1057. No abstract available.

  PMID: 9717033 RESULT

• Gurm HS, Dixon SR, Smith DE, Share D, Lalonde T, Greenbaum A, Moscucci M; BMC2 (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) Registry. Renal function-based contrast dosing to define safe limits of radiographic contrast media in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2011 Aug 23;58(9):907-14. doi: 10.1016/j.jacc.2011.05.023.

  PMID: 21851878 RESULT

• Ware LB, Matthay MA. Clinical practice. Acute pulmonary edema. N Engl J Med. 2005 Dec 29;353(26):2788-96. doi: 10.1056/NEJMcp052699. No abstract available.

  PMID: 16382065 RESULT

• Dorval JF, Dixon SR, Zelman RB, Davidson CJ, Rudko R, Resnic FS. Feasibility study of the RenalGuard balanced hydration system: a novel strategy for the prevention of contrast-induced nephropathy in high risk patients. Int J Cardiol. 2013 Jun 20;166(2):482-6. doi: 10.1016/j.ijcard.2011.11.035. Epub 2011 Dec 26.

  PMID: 22204847 RESULT

• 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.

  PMID: 22230154 RESULT

• 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.

  PMID: 39878152 DERIVED

Study Officials

• Carlo Briguori

  Clinica Mediterranea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 8, 2015
• First Posted: July 3, 2015
• Study Start: July 15, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: September 7, 2018

Record last verified: 2018-09