DyeVert System and Contrast-induced Acute Kidney Injury

Acute Coronary Syndromes Clinical Trial

— REMEDIALIV  

Official title:

Renal Insufficiency Following Contrast Media Administration Trial IV: Contrast Media Volume Control for Limiting Contrast-Induced Acute Kidney in Acute Coronary Syndrome.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04714736
• Other study ID #: NCT006
• Status: Completed
• Phase: N/A
• Start date: February 10, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2024
• Source: Clinica Mediterranea
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the REnal Insufficiency Following Contrast MEDIA Administration TriaL IV (REMEDIAL IV) is to test whether the use of the DyeVert system is effective in reducing CI-AKI rate in ACS patients undergoing urgent/immediate (within 2 hours) invasive diagnostic and/or interventional cardiovascular procedures. The DyeVert™ system (Osprey Medical Inc., Minnetonka, MN, USA) is a novel device designed to reduce CM volume during coronary procedures, while maintaining fluoroscopic image quality. Patients with ACS scheduled for urgent/immediate coronary angiography/angioplasty will be enrolled and randomized into 2 groups: 1) DyeVert group (CM injection will be handled by the DyeVert TM system), and 2) Control group (CM injection will be carried out by a conventional manual injection syringe).

Description:

Acute kidney injury (AKI) is a common complication in patients suffering from acute coronary syndromes (ACS) and treated by percutaneous coronary intervention (PCI). This complication has been associated with higher early and late adverse events. It has been emphasized that the pathogenesis of AKI in the setting of ACS is multifactorial, including age, unstable hemodynamic conditions, co-morbidities (that is, diabetes mellitus and anemia) pre-existing chronic kidney disease, dehydration and administration of nephrotoxic drugs. However, the role of iodinated contrast media (CM) has been well established. Hydration represents the cornerstone in contrast-induced AKI (CI-AKI) prevention. However, at present there is no consensus on how hydration should be carried out, especially in ACS patients, and all the the recommended hydration regimens have limited applicability in the urgent/emergent settings such as ACS. Several targeted hydration regimens have been proposed, but none has been tested in ACS patients; in the present trial the investigators will adopt the left ventricular end diastolic pressure (LVEDP) -guided hydration because this approach is simple and easy to implement in the current target population. The CM volume used is an independent predictor of CI-AKI and the concept that "the lower the CM volume, the lower the CI-AKI risk" is generally accepted. The administration of a CM volume >3X glomerular filtration rate (GFR) is suggestive of increased risk of CI-AKI. To date the use of manual injections with a manifold remains the preferred technique in the majority of catheterization laboratories. In particular, manual injection is often favored for interventional procedures, which require low, variable-flow pressure injections. The AVERT trial demonstrated that CM volume is significantly lower in patients randomized to DyeVert™ in comparison to control (36.9 ± 10.9 mL versus 62.5 ± 12.7 mL, p < 0.001) and the observed reduction in CM volume used was most evident in patients undergoing PCI. Therefore, in this scenario is of outmost importance to limit the CM volume in the attempt to prevent CI-AKI. The aim of the REnal Insufficiency Following Contrast MEDIA Administration TriaL IV (REMEDIAL IV) is to test whether the use of the DyeVert system is effective in reducing CI-AKI rate in ACS patients undergoing urgent or immediate (within 2 hours) invasive diagnostic and/or interventional cardiovascular procedures. METHODS All patients with ACS scheduled for urgent/immediate coronary angiography/angioplasty will be screened for inclusion/exclusion criteria. Diagnosis of ACS (both ST-Elevation Myocardial Infarction [STEMI] and high-risk Non-ST-Elevation Myocardial Infarction [Non-STEMI]) will be established in accordance with guidelines, including a typical chest pain history, diagnostic electrocardiographic changes, and serial increase of cardiac biomarkers. All patients with inclusion/exclusion criteria satisfied and who will agree to sign the informed consent will be enrolled into the trial. The REMEDIAL IV trial will be conducted at a pool of Italian interventional cardiology centers, according to the principles of the Declaration of Helsinki and Good Clinical Practice and has been approved by the local Ethic Committees. All the patients included into the study will receive intravenous 0.9% sodium chloride as soon as in the catheterization laboratory; the hydration regimen will be defined according to the hemodynamic conditions, as defined below. The patients will be then randomized into 2 groups: 1) DyeVert group, and 2) Control group. STUDY ENDPOINTS The primary endpoint of the trial is the rate of CI-AKI. CI-AKI is defined as an increase in the serum creatinine (sCr) concentration ≥ 0.3 mg/dL from the baseline value within 5 days after CM administration or the need for dialysis. Secondary end-points will include: 1) differences in the CM volume in the 2 groups; 2) an increase in the sCr concentration ≥25% within 5 days after CM exposure; 4) the severity of AKI assessed according to the Acute Kidney Injury Network criteria: Stage 1, a sCr increase ≥0.3 mg/dL or ≥1.5-1.9 times from baseline; Stage 2, a sCr increase ≥2.0-2.9 times from baseline; and Stage 3, a sCr increase ≥3.0 times from baseline or the need for dialysis; 5) changes in the serum cystatin C concentration at 24 and 48 hours after CM exposure; 6) the rate of acute renal failure requiring dialysis (defined as a decrease in renal function necessitating acute hemodialysis, ultrafiltration or peritoneal dialysis within the first 5 days post-intervention); 7) the rate of in-hospital, 6 and 12-month major adverse events (MAE), including death, renal failure requiring dialysis, acute pulmonary edema, and sustained kidney injury. Sustained kidney injury is defined as a persistent ≥25% GFR reduction compared to baseline at 6 and 12 months; and 8) the length in in-hospital stay, calculated as the sum of the number of days since admission until discharge from the hospital.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 522
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Urgent or immediate (within 2 hours) coronary procedure with iodinated contrast media administration in the setting of an acute coronary syndrome: ST-Elevation Myocardial Infarction (according to Fourth Universal Definition of Myocardial Infarction);

High-risk Non-ST-Elevation Myocardial Infarction (according to current guidelines):

1. Refractory angina,

2. Signs or symptoms of heart faiklure or new or worsening mitral regurgitation,

3. Hemodynamic instability,

4. Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy,

5. Sustained ventricular tachycardia or ventricular fibrillation,

6. Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation.

Exclusion Criteria:

• Women who are pregnant.
• Recent contrast media exposure: contrast media exposure within 48 hours.
• End-stage chronic kidney disease on chronic dialysis: both haemodialysis and peritoneal dialysis.
• Multiple myeloma.
• Current enrolment in any other study when enrolment in the REMEDIAL IV would involve deviation from either protocol.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Coronary Syndromes
• Acute Kidney Injury
• Contrast-induced Acute Kidney Injury
• Syndrome

Intervention

Device:
• Coronary angiography using DyeVert system
Invasive diagnostic and/or interventional cardiovascular procedures in the setting of acute coronary syndrome using DyeVert system.

Procedure:
• Coronary angiography using conventional manual injection syringe.
Invasive diagnostic and/or interventional cardiovascular procedures in the setting of acute coronary syndrome using conventional manual injection syringe.

Locations

Country	Name	City	State
Italy	IRCCS Policlinico Multimedica	Milan
Italy	Clinica Mediterranea	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Mediterranea

Country where clinical trial is conducted

Italy, 

References & Publications (32)

Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ. 2014 AHA/ACC Guideline for the Management of Patients — View Citation

Ando G, Cortese B, Russo F, Rothenbuhler M, Frigoli E, Gargiulo G, Briguori C, Vranckx P, Leonardi S, Guiducci V, Belloni F, Ferrari F, de la Torre Hernandez JM, Curello S, Liistro F, Perkan A, De Servi S, Casu G, Dellavalle A, Fischetti D, Micari A, Loi — View Citation

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;3 — View Citation

Briguori C, Quintavalle C, De Micco F, Visconti G, Di Palma V, Napolitano G, Focaccio A, Condorelli G. Persistent serum creatinine increase following contrast-induced acute kidney injury. Catheter Cardiovasc Interv. 2018 Jun;91(7):1185-1191. doi: 10.1002/ — View Citation

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 pat — View Citation

Desch S, Fuernau G, Poss J, Meyer-Saraei R, Saad M, Eitel I, Thiele H, de Waha S. Impact of a novel contrast reduction system on contrast savings in coronary angiography - The DyeVert randomised controlled trial. Int J Cardiol. 2018 Apr 15;257:50-53. doi: — View Citation

Freeman RV, O'Donnell M, Share D, Meengs WL, Kline-Rogers E, Clark VL, DeFranco AC, Eagle KA, McGinnity JG, Patel K, Maxwell-Eward A, Bondie D, Moscucci M; Blue Cross-Blue Shield of Michigan Cardiovascular Consortium (BMC2). Nephropathy requiring dialysis — View Citation

Giacoppo D, Madhavan MV, Baber U, Warren J, Bansilal S, Witzenbichler B, Dangas GD, Kirtane AJ, Xu K, Kornowski R, Brener SJ, Genereux P, Stone GW, Mehran R. Impact of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention on Short- — View Citation

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 u — View Citation

Gurm HS, Seth M, Kooiman J, Share D. A novel tool for reliable and accurate prediction of renal complications in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2013 Jun 4;61(22):2242-8. doi: 10.1016/j.jacc.2013.03.026. — View Citation

Gurm HS, Seth M, Mehran R, Cannon L, Grines CL, LaLonde T, Briguori C; Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). Impact of Contrast Dose Reduction on Incidence of Acute Kidney Injury (AKI) Among Patients Undergoing PCI: A Modeli — View Citation

Hwang JR, D'Alfonso S, Kostuk WJ, Diamantouros P, Teefy P, Jablonsky G, Lavi S. Contrast volume use in manual vs automated contrast injection systems for diagnostic coronary angiography and percutaneous coronary interventions. Can J Cardiol. 2013 Mar;29(3 — View Citation

Leoncini M, Toso A, Maioli M, Tropeano F, Villani S, Bellandi F. Early high-dose rosuvastatin for contrast-induced nephropathy prevention in acute coronary syndrome: Results from the PRATO-ACS Study (Protective Effect of Rosuvastatin and Antiplatelet Ther — View Citation

Maioli M, Toso A, Leoncini M, Micheletti C, Bellandi F. Effects of hydration in contrast-induced acute kidney injury after primary angioplasty: a randomized, controlled trial. Circ Cardiovasc Interv. 2011 Oct 1;4(5):456-62. doi: 10.1161/CIRCINTERVENTIONS. — View Citation

Marenzi G, Assanelli E, Campodonico J, Lauri G, Marana I, De Metrio M, Moltrasio M, Grazi M, Rubino M, Veglia F, Fabbiocchi F, Bartorelli AL. Contrast volume during primary percutaneous coronary intervention and subsequent contrast-induced nephropathy and — View Citation

Marenzi G, Lauri G, Assanelli E, Campodonico J, De Metrio M, Marana I, Grazi M, Veglia F, Bartorelli AL. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction. J Am Coll Cardiol. 2004 Nov 2;44(9):1780-5. d — View Citation

Mariani J Jr, Guedes C, Soares P, Zalc S, Campos CM, Lopes AC, Spadaro AG, Perin MA, Filho AE, Takimura CK, Ribeiro E, Kalil-Filho R, Edelman ER, Serruys PW, Lemos PA. Intravascular ultrasound guidance to minimize the use of iodine contrast in percutaneou — 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. 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 v — View Citation

Mehran R, Faggioni M, Chandrasekhar J, Angiolillo DJ, Bertolet B, Jobe RL, Al-Joundi B, Brar S, Dangas G, Batchelor W, Prasad A, Gurm HS, Tumlin J, Stone GW. Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury — View Citation

Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for ca — View Citation

Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi: 10.1186/cc5713. — View Citation

Naidu SS, Aronow HD, Box LC, Duffy PL, Kolansky DM, Kupfer JM, Latif F, Mulukutla SR, Rao SV, Swaminathan RV, Blankenship JC. SCAI expert consensus statement: 2016 best practices in the cardiac catheterization laboratory: (Endorsed by the cardiological so — View Citation

Narula A, Mehran R, Weisz G, Dangas GD, Yu J, Genereux P, Nikolsky E, Brener SJ, Witzenbichler B, Guagliumi G, Clark AE, Fahy M, Xu K, Brodie BR, Stone GW. Contrast-induced acute kidney injury after primary percutaneous coronary intervention: results from — 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. No abstract available. — View Citation

Nayak KR, Mehta HS, Price MJ, Russo RJ, Stinis CT, Moses JW, Mehran R, Leon MB, Kandzari DE, Teirstein PS. A novel technique for ultra-low contrast administration during angiography or intervention. Catheter Cardiovasc Interv. 2010 Jun 1;75(7):1076-83. do — View Citation

Qian G, Fu Z, Guo J, Cao F, Chen Y. Prevention of Contrast-Induced Nephropathy by Central Venous Pressure-Guided Fluid Administration in Chronic Kidney Disease and Congestive Heart Failure Patients. JACC Cardiovasc Interv. 2016 Jan 11;9(1):89-96. doi: 10. — View Citation

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group. 2015 — View Citation

Ronco C, Cicoira M, McCullough PA. Cardiorenal syndrome type 1: pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am Coll Cardiol. 2012 Sep 18;60(12):1031-42. doi: 10.101 — View Citation

Sadick V, Reed W, Collins L, Sadick N, Heard R, Robinson J. Impact of biplane versus single-plane imaging on radiation dose, contrast load and procedural time in coronary angioplasty. Br J Radiol. 2010 May;83(989):379-94. doi: 10.1259/bjr/21696839. Epub 2 — 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. doi: 10.1056/NEJM199411243312104. — View Citation

Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task — View Citation

* Note: There are 32 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of contrast-induced Acute Kidney Injury (CI-AKI).	Serum creatinine (mg(dL) is assessed at baseline (before coronary intervention) and then every day during the hospital stay. CI-AKI is defined as a change in the serum creatinine concentration =0.3 mg/dL from the baseline value within 5 days after contrast media administration or the need for dialysis.	30 days
Secondary	Differences in the contrast media volume in the 2 groups.	Volume of contrast media utilized (mL) is assessed in all enrolled patients at the end of the procedure	30 days
Secondary	Change in the sCr concentration = 25 percent within 5 days after CM exposure.	Serum creatinine (mg(dL) is assessed at baseline at baseline (before coronary intervention) and therefore every day during the hospidal stay	30 days
Secondary	Severity of AKI assessed according to the Acute Kidney Injury Network criteria.	Stage 1, a sCr change =0.3 mg/dL or =1.5-1.9 times from baseline; Stage 2, a sCr change =2.0-2.9 times from baseline; Stage 3, a sCr change =3.0 times from baseline or the need for dialysis.	30 days
Secondary	Changes in the serum cystatin C concentration at 24 and 48 hours after CM exposure.	Serum Cystatin C (mg/dL) is assessed at baseline (before the coronary procedure) and at 24 and 48 hours after the procedure	48 hours
Secondary	Rate of acute renal failure requiring dialysis.	Change in renal function necessitating acute hemodialysis, ultrafiltration or peritoneal dialysis within the first 5 days post intervention.	5 days
Secondary	Rate of in-hospital, 6 and 12 month major adverse events (MAE).	MAE include death, renal failure requiring dialysis, acute pulmonary edema, and sustained kidney injury (defined as a persistent =25% GFR change compared to baseline at 6 and 12 months	12 months
Secondary	Length of in-hospital stay.	In-hospital stay calculated as the sum of the number of days since admission until discharge from the hospital.	30 days