PrevenTion of Contrast-inducEd nephroAThy With urinE Alkalinization

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-31

Study Completion Date

2021-05-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Does Bicarbonate in Addition to Theophylline Reduce CIN?

NCT02643602

Radiographic Contrast Agent Nephropathy

COMPLETED NA

Oral Versus Intravenous Hydration to Prevent Contrast Induced Nephropathy

NCT01093131

Contrast Induced Nephropathy

WITHDRAWN PHASE4

Effect of Sodium Bicarbonate Solution in Decreasing the Incidence of Contrast Induced Nephropathy (CIN)

NCT00514150

Contrast Induced Nephropathy

COMPLETED PHASE3

Preventing contrAst Induced Nephropathy After TranscathEter Aortic Valve Replacement

NCT03121053

Aortic Valve Disease Chronic Kidney Disease Contrast Induced Nephropathy +1 more

UNKNOWN PHASE4

Sodium Bicarbonate Versus Saline for the Prevention of Contrast-induced Nephropathy

NCT00606827

Contrast-Induced Nephropathy

COMPLETED PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Contrast medium-induced nephropathy (CIN) is a recognized complication in coronary diagnostic and interventional procedures, and is associated with prolonged hospitalization and adverse clinical outcomes. The frequency of CIN ranges from 2% in low-risk patients to 50% in high-risk patients. The most important risk factors for CIN development are pre-existing renal failure, diabetes, age, volume and type of contrast medium. There are two main pathogenetic mechanisms postulated to cause CIN:

1. a direct toxic action of contrast medium on kidney tubule cells, causing a disruption of mitochondrial function, the generation of reactive oxygen species, and subsequent cell injury and apoptosis;
2. vasoconstriction, reducing the blood flow through the renal medulla and causing ischemia with cell damage The treatment of CIN is exclusively supportive. Treatment is particularly recommended in patients with chronic kidney disease (CKD - mild, moderate or severe, according to estimated glomerular filtration rate - eGFR). Several approaches have been tested in the prevention of CIN with variable success. Adequate hydration is widely accepted as the best method for prevention of CIN, and is today the only strategy generally accepted by international guidelines (class of recommendation I, level of evidence A). The use of N-acetyl cysteine, recommended even in the recent past, is not supported by a recent randomized trial14 and a meta-analysis. Hemodialysis and hemofiltration may be effective in preventive CIN, but are reserved to high-risk patients. Attempts at preventing CIN with various medications, such as furosemide, vitamin C, statins and numerous other, have been largely unsuccessful. The efficacy of bicarbonate in the prevention of CIN has been extensively tested; the rationale is here that urine alkalinization suppresses the formation of free radicals. Actually, studies on bicarbonate have been controversial, varying from beneficial to toxic effects; this could bring into question the role of alkalinizing procedures in preventing CIN. Nevertheless, favorable results of prevention protocols using bicarbonate have been noted in studies also documenting a significant alkalinization of urines; while a similar protocol did not prove to be effective when the dose of bicarbonate was insufficient to such aim. Moreover, Markota et al., in a recent study on patients with estimated eGFR \>15 mL/min/1.73 m2 and scheduled for coronary angiography, after documenting that Na/K citrate significantly reduced the incidence of CIN when compared with hydration alone, have shown that patients having a urine pH \<6 had a more than ten-fold higher incidence of CIN compared with patients whose urine pH was \>6.28 These results confirm the potential role of urine alkalinization in preventing CIN and place the oral administration of alkalinizing drugs as an attractive method compared to the more complex, and not always effective, i.v. infusion of bicarbonate. Finally, oral doses of bicarbonate may be sufficient to alkalinize the urine and thus to prevent CIN. In a study recently published, an oral dose of 4 g was sufficient to obtain, two hours after administration, an adequate urinary alkalinization with a pH \>7 in all participants without side effects. This value was maintained and even magnified nearly 8 hours after the last dose. Interestingly, the Authors observed an additive effect after the second dose, showing a nondepleting urine pH, despite the reported short half-life of sodium bicarbonate.

Against this background, the investigators will here test the hypothesis that both oral and i.v. bicarbonate are adequate strategies for CIN prevention in patients after coronary angiography. Comparing the incidence of CIN according to urine pH achieved immediately before angiography, the investigators aim at demonstrating that urine alkalinization is the real goal, and that results are here largely independent from the strategy adopted to achieve it. The investigators will therefore compare the efficacy in alkalinizing urine and preventing CIN of three different strategies: hydration alone; hydration plus i.v. sodium bicarbonate; and hydration plus oral bicarbonate. Favorable results of the bicarbonate groups compared to the control group could increase the evidence supporting the use of alkalinizing strategies to prevent CIN; at the same time, non-inferiority results of the oral group compared to i.v. bicarbonate group could suggest the more practical oral administration as the preferred prevention strategy.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Kidney Injury Contrast Media Reaction

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

isotonic saline

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

Group Type ACTIVE_COMPARATOR

isotonic saline

Intervention Type DRUG

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

i.v. sodium bicarbonate

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.

Group Type ACTIVE_COMPARATOR

i.v. sodium bicarbonate

Intervention Type 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.

oral sodium bicarbonate:

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.

Group Type EXPERIMENTAL

oral sodium bicarbonate

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

isotonic saline

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

Intervention Type DRUG

i.v. sodium bicarbonate

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.

Intervention Type DRUG

oral sodium bicarbonate

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Isotonic sodium chloride solution HCO3 HCO3

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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).

Exclusion Criteria

* 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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No