PrevenTion of Contrast-inducEd nephroAThy With urinE Alkalinization

NCT02980003 | Completed Phase 3 DMC

• 1 other identifier: TEATE study
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Intravascular administration of iodinated contrast media is an essential tool for cardiovascular imaging and percutaneous coronary interventions. Nonetheless, the increasing incidence of contrast-induced nephropathy (CIN) has become an important and prognostically relevant problem along with the spreading of diagnostic and interventional procedures. CIN is largely dependent on oxidative damage and represents a considerable cause of renal failure, being associated with prolonged hospitalization and significant morbidity/mortality. The most effective treatment strategy of this serious complication remains prevention, and several preventive measures have been extensively investigated in the last few years. Pre-procedural hydration is the best known and mostly accepted strategy. The administration of sodium bicarbonate (HCO3) has controversial effects, and is likely to be ineffective when the infused dose is unable to achieve adequate urine alkalinization. Since alkaline pH suppresses the production of free radicals, increasing urine pH would be an attractive goal for CIN prevention. In a randomized clinical trial the investigators will test the hypothesis that urine alkalinization with either oral or i.v. bicarbonate on top of hydration alone is the main determinant of CIN prevention in a population of patients with moderate or severe chronic kidney disease scheduled for coronary angiography and/or angioplasty. If the investigators, demonstrate non-significant differences in urine alkalinization (primary endpoint) and incidence of CIN (secondary endpoint) between the bicarbonate groups, a practical implication will be that oral administration is preferable for practical reasons over the administration of i.v. bicarbonate.

Conditions

Acute Kidney Injury; Contrast Media Reaction

Keywords

contrast media; contrast-induced acute kidney injury (AKI); contrast-induced nephropathy (CIN)

Outcome Measures

Primary Outcomes (1)

• The incidence of CIN according to urine alkalinization achieved immediately before angiography

  The investigators primary hypothesis is that the incidence of CIN definition is significantly different in patients achieving urine alkalinization compared with patients not achieving it.

  48 hours after randomization

Secondary Outcomes (4)

• Urine PH

  48 hours after randomization

• the incidence of CIN in three treatment groups

  48 hours after coronary angiography

• non-inferiority comparison between oral sodium bicarbonate group and i.v. sodium

  48 hours after coronary angiography

• non-inferiority comparison between oral sodium bicarbonate group and i.v. sodium bicarbonate

  48 hours after coronary angiography

Study Arms (3)

isotonic saline

ACTIVE COMPARATOR

patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. The infusion rate will be 1 mL/kg/h in the first 5 hours they will receive isotonic saline at 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction \<35% or New York Heart Association (NYHA) functional class III or IV). Then, will be infused at 3 mL/kg/h for 1 hour immediately before contrast medium injection; following this, patients will receive the same fluid at a rate of 1 mL/kg/h

Drug: isotonic saline

i.v. sodium bicarbonate

ACTIVE COMPARATOR

in the first 5 hours patients will receive isotonic saline at 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction \<35% or NYHA functional class III or IV). Then, a solution of 1.4% sodium bicarbonate (167 mEq/L; 334 milliosmol (mOsm/L)) will be infused: the initial intravenous bolus will be 3 mL/kg/h for 1 hour immediately before contrast medium injection; following this, patients will receive the same fluid at a rate of 1 mL/kg/h (reduced to 0.5 mL/kg/h if with ejection fraction \<35% or NYHA functional class III or IV) during the exposure to contrast and for 6 hours after the procedure. Later, patients will resume hydration with isotonic saline for further 6 hours.

Drug: i.v. sodium bicarbonate

oral sodium bicarbonate:

EXPERIMENTAL

patients will start hydration with isotonic saline as well as Arm Hydration Alone. One hour before the angiography and 3 hours after patients will receive oral sodium bicarbonate at the dose of 4 g (47.6 mEq) dissolved in 60 mL of water. The drug will be weighed with a precision balance with a sensitivity of ± 0.1 mg and placed in a labeled sterile plastic container. The label will report the lot number, expiry date of the sodium bicarbonate lot, the signature of the pharmacist carrying out the weighing process, a serial number to identify the sample and the patient identification number. Documentation will be stored in the Laboratory of Galenic Preparations, Pharmacy Division, of the hospital.

Drug: oral sodium bicarbonate

Interventions

isotonic saline DRUG

patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure.

Also known as: Isotonic sodium chloride solution

isotonic saline

i.v. sodium bicarbonate DRUG

patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. The patient receives solution of 1.4% sodium bicarbonate (167 mEq/L; 334 mOsm/L) one hours and six hours after procedure.

Also known as: HCO3

i.v. sodium bicarbonate

oral sodium bicarbonate DRUG

patients will start hydration with isotonic saline 6 hours before angiography and continue for 12 hours after the procedure. One hour before the angiography and 3 hours after patients will receive oral sodium bicarbonate at the dose of 4 g (47.6 mEq) dissolved in 60 mL of water

Also known as: HCO3

oral sodium bicarbonate:

Eligibility Criteria

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

You may qualify if:

• Consecutive patients scheduled for coronary angiography and/or angioplasty;
• eGFR \<60 mL/min/1.73 m2, but \>15 mL/min/1.73 m2 (MDRD formula).

You may not qualify if:

• acute renal insufficiency;
• emergency catheterization (e.g., STEMI patients) preventing the possibility of pretreatments;
• a history of adverse reactions to contrast media;
• use of potentially nephrotoxic drugs (non-steroidal anti-inflammatory drugs, aminoglycosides, sulphonamides, cyclosporin, tacrolimus, methotrexate or platinum complexes) from 48 hours before to 24 hours after the procedure, but allowing drugs deemed essential for cardiovascular therapy (diuretics, acetylsalicylic acid, angiotensinconverting enzyme inhibitors, angiotensin receptor blockers or aliskiren);
• pulmonary edema;
• multiple myeloma and other monoclonal gammopathies;
• factors predisposing to kidney injury: diarrhea, vomiting, dehydration or bleeding;
• exposure to contrast media within 7 days before the procedure; pregnancy; -
• hypersensitivity to the active substance or to any of the excipients;
• Metabolic or respiratory alkalosis, particularly if hypochloremic (vomiting, gastrointestinal losses, diuretic therapy);
• Hypocalcemia;
• use of N-acetyl cysteine, theophylline, dopamine, fenoldopam, mannitol, citrate or bicarbonate within 48 hours before coronary angiography;
• Chronic and / or acute therapy with corticosteroid, quinidine, ephedrine and pseudoephedrine;
• urinary tract infections.

Sponsors & Collaborators

• G. d'Annunzio University: lead

Study Sites (1)

Institute of Cardiology - Center of Excellence on Aging, G. d'Annunzio University

Chieti, CH, 66100, Italy

Location

Related Publications (5)

• Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, Withers J, Farid N, McManamon PJ. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med. 1989 Jan 19;320(3):143-9. doi: 10.1056/NEJM198901193200303.

  PMID: 2643041 RESULT

• 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 RESULT

• Markota D, Markota I, Starcevic B, Tomic M, Prskalo Z, Brizic I. Prevention of contrast-induced nephropathy with Na/K citrate. Eur Heart J. 2013 Aug;34(30):2362-7. doi: 10.1093/eurheartj/eht009. Epub 2013 Jan 24.

  PMID: 23349296 RESULT

• Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002 May 14;105(19):2259-64. doi: 10.1161/01.cir.0000016043.87291.33.

  PMID: 12010907 RESULT

• Lombardi M, Molisana M, Genovesi E, De Innocentiis C, Limbruno U, Misuraca L, Moretti L, Di Vito L, Renda G, Zimarino M, Di Nicola M, De Caterina R. Urine alkalinisation to prevent contrast-induced acute kidney injury: the prospective, randomised, controlled, open-label TEATE trial. EuroIntervention. 2022 Sep 20;18(7):562-573. doi: 10.4244/EIJ-D-22-00010.

  PMID: 35620986 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Sodium Chloride; Sodium Bicarbonate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic

Study Officials

• Raffaele De Caterina

  G. d'Annunzio University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 5, 2016
• First Posted: December 2, 2016
• Study Start: March 1, 2015
• Primary Completion: October 30, 2020
• Study Completion: May 1, 2021
• Last Updated: May 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)