Sodium Bicarbonate and N-Acetylcysteine for Nephroprotection in Acute Myocardial Infarction

Acute Kidney Injury Clinical Trial

— BINARIO  

Official title:

BIcarbonato di Sodio e N-Acetilcisteina Nella Prevenzione Della Nefropatia da Mezzo di Contrasto Nell'infaRto mIocardico acutO(Registro BINARIO)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01218178
• Other study ID #: P/479/CE/2010
• Status: Completed
• Phase: Phase 3
• First received: October 4, 2010
• Last updated: March 12, 2015
• Start date: June 2008
• Est. completion date: October 2011

Study information

• Verified date: March 2015
• Source: Catholic University of the Sacred Heart
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Observational

Clinical Trial Summary

Contrast-induced nephropathy (CIN) represents a potential complication of diagnostic and therapeutic procedures in interventional cardiology, especially in the acute setting of primary PCI. The investigators will test the efficacy of sodium bicarbonate (NaHCO3) and N-acetylcysteine (NAC) on the prevention of acute events and CIN in patients with acute myocardial infarction.

Description:

Introduction Contrast-induced nephropathy (CIN) represents a potential complication of diagnostic and therapeutic procedures in interventional cardiology. In the setting of elective procedures, the strategy of sodium bicarbonate (NaHCO3) and N-acetylcysteine (NAC) infusion has been shown to reduce the incidence of CIN in high-risk patients. The efficacy of this strategy has not been demonstrated in the case of primary percutaneous coronary intervention (PCI).

Aim of the study The aim is to assess the efficacy of the strategy of sodium bicarbonate 154mEq/l + glucose solution 5% (infusion rate: 3 mL • kg-1 • h-1 for 1 hour followed by 1 mL

• kg-1 • h-1 for 6 hours) and NAC (1200 mg i.v. followed by 1200 mg bid for the next 48 hours) in reducing the incidence of CIN in patients with STEMI undergoing primary or rescue PCI. As control group, a population of STEMI patients treated with NAC (1200 mg i.v. followed by 1200 mg bid for the next 48 hours) + conventional hydration with saline solution 0.9% will be retrospectively enrolled. According to the common definition, CIN will be defined as increase of the level of serum creatinine >0,5 mg/dL and/or increase ≥25% serum creatinine and/or decrease ≥25% of the glomerular filtration rate (GFR) as calculated with the MDRD Modification of Diet in Renal Disease)formula at 48 hours after PCI compared with baseline value after primary PCI.

Study Design This is a two-center (Policlinico Gemelli and Policlinico Casilino, Rome, Italy), prospective, spontaneous (not sponsored) observational study.

Patient population

Inclusion criteria:

• Consecutive patients with ST-Segment Elevation Myocardial Infarction (STEMI) as diagnosed according to the ACC (American College of Cardiology) criteria:

• ischemic symptoms;

• ECG variations: ST-elevation (>0,05 mV) in two or more contiguous leads;

• Increase of the biochemical markers of myocardial necrosis (troponin T, cTNT).

• Indication to urgent coronary angiography and primary or rescue PCI

Exclusion criteria:

• Patients with history of allergic reaction to NAC (Fluimucil, Zambon Group Spa, Milan, Italy)

• Chronic hemodialysis

• Age > 90 years

Study protocol Patients will be treated with 154 mEq/L of sodium bicarbonate and glucose 5% solution (infusion rate of 3 mL • kg-1 • h-1 for 1 hour followed by 1 mL • kg-1 • h-1 for 6 hours) plus NAC (1200 mg i.v. followed by 1200 mg bid for the next 48 hours). As control group, a population of STEMI patients treated with conventional hydration with saline solution 0,9% and NAC (1200 mg i.v. followed by 1200 mg bid for the next 48 hours) according to the common clinical practice of the Department of Cardiovascular Medicine of the Policlinico Agostino Gemelli and of Cardiology Department of the Policlinico Casilino will be retrospectively enrolled.

Endpoints:

Primary endpoint:

• Composite endpoint (death/need for dialysis/CIN)

Secondary endpoints:

• assessment of individual major adverse events (death, re-infarction, need for dialysis) during at 1, 6 and 12 months

• assessment of the incidence of CIN defined as increase of the level of serum creatinine >0,5 mg/dL and/or increase ≥25% serum creatinine and/or decrease ≥25% of the glomerular filtration rate (GFR) as calculated with the MDRD formula at 48 hours after PCI compared with baseline value.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 520
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• ST-Segment Elevation Myocardial Infarction (STEMI) as diagnosed according to the ACC (American College of Cardiology) criteria:

• ischemic symptoms;

• ECG variations: ST-elevation (>0,05 mV) in two or more contiguous leads;

• Increase of the biochemical markers of myocardial necrosis (troponin T, cTNT). • Indication to urgent coronary angiography and primary or rescue PCI

Exclusion Criteria:

• Patients with history of allergic reaction to NAC

• Chronic hemodialysis

• Age >= 90 years

Study Design

Observational Model: Case Control

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Sodium bicarbonate plus NAC
154 mEq/L sodium bicarbonate (infusion rate of 3 ml/Kg for 1 hour followed by 1 ml/Kg for 6 hours) plus NAC (1200 mg bid for 48 hours)
• Saline hydration plus NAC
0.9% saline (1 ml/Kg for 12 hours) plus NAC (1200 mg bid for 48 hours)

Locations

Country	Name	City	State
Italy	Policlinico Agostino Gemelli and Policlinico Casilino	Rome

Sponsors (2)

Lead Sponsor	Collaborator
Catholic University of the Sacred Heart	Policlinico Casilino ASL RMB

Country where clinical trial is conducted

Italy, 

References & Publications (16)

Adolph E, Holdt-Lehmann B, Chatterjee T, Paschka S, Prott A, Schneider H, Koerber T, Ince H, Steiner M, Schuff-Werner P, Nienaber CA. Renal Insufficiency Following Radiocontrast Exposure Trial (REINFORCE): a randomized comparison of sodium bicarbonate versus sodium chloride hydration for the prevention of contrast-induced nephropathy. Coron Artery Dis. 2008 Sep;19(6):413-9. doi: 10.1097/MCA.0b013e3283021ac6. — View Citation

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

Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem. 2000 Aug 18;275(33):25130-8. — 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

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16;130(6):461-70. — View Citation

Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. 2006 Jun 29;354(26):2773-82. — 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. — 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

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

Navaneethan SD, Singh S, Appasamy S, Wing RE, Sehgal AR. Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Am J Kidney Dis. 2009 Apr;53(4):617-27. doi: 10.1053/j.ajkd.2008.08.033. Epub 2008 Nov 22. Review. — View Citation

Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, Aslan O, Badak O. Sodium bicarbonate, N-acetylcysteine, and saline for prevention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single-center prospective controlled trial. Am Heart J. 2007 Sep;154(3):539-44. — 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. The role of osmolality in the incidence of contrast-induced nephropathy: a systematic review of angiographic contrast media in high risk patients. Kidney Int. 2005 Nov;68(5):2256-63. 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

Wright RS, Reeder GS, Herzog CA, Albright RC, Williams BA, Dvorak DL, Miller WL, Murphy JG, Kopecky SL, Jaffe AS. Acute myocardial infarction and renal dysfunction: a high-risk combination. Ann Intern Med. 2002 Oct 1;137(7):563-70. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All cause mortality, contrast-induced nephropathy and need of dialysis.	To test the efficacy of sodium bicarbonate plus N-acetylcysteine vs saline hydration plus N-acetylcysteine to reduce mortality and to prevent contrast-induced nephropathy in the setting of primary PCI.	2010	Yes