Bicarbonate v Saline to Prevent Contrast Nephropathy

Phase 4 Study of Bicarbonate Versus Saline Infusion Therapy to Prevent Contrast Induced Nephropathy (CAN-IT PREVENT Protocol)

Slowing of kidney function occurs in a minority of people given dye during angiography. The purpose of this study is to compare two different types of fluid given into a vein to reduce the risk of kidney injury: salt in water or baking soda in water.

Study Overview

• Status: Terminated
• Conditions: Kidney Failure, Acute; Contrast Media
• Intervention / Treatment: Drug: 1/6 M (166 mEq/L) IV Sodium Bicarbonate; Drug: 0.9% (154 mEq/L) IV Sodium Chloride

Detailed Description

A decline in kidney function after contrast is associated with prolonged hospital stay, adverse cardiac events, and higher mortality both in hospital and in the long term. Deliberate administration of fluids is recommended to reduce the risk of contrast nephropathy. However, data to support specific recommendations are lacking and the optimal fluid regimen remains unclear.

It has been hypothesized that alkalinization of tubular fluid might be beneficial by reducing pH dependent free radical levels. A recent trial found a lower frequency of creatinine rise > 25% within two days of contrast with a 7 hour infusion of isotonic sodium bicarbonate than with saline infusion (Merten GJ, JAMA 2004). However, it remains to be proven that bicarbonate is superior as this trial has a number of methodological flaws.

Comparison: IV 1/6 M sodium bicarbonate OR IV 0.9% saline, each isotonic fluid given at the same rate of sodium administration (3.25 ml/Kg over 1 hour pre-contrast, followed by 1.1 ml/Kg/hr for 6 hours for bicarbonate; 3.5 ml/Kg over 1 hour pre-contrast, followed by 1.2 ml/Kg/hr for 6 hours for saline). Total infusion time 7 hours (for both). Maximum rate of fluid permitted is that for a body weight of 110 Kg. Intra-vascular iso- or low-osmolality contrast in the minimal dose needed to complete the required imaging.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy, 25100
    • Spedali Civili di Brescia
  • Catania, Italy, 95100
    • Ospedale Ferrarotto
  • Cernusco sul Naviglio, Italy, 20063
    • P.O. Uboldo
  • Cremona, Italy, 26100
    • Azienda Istituti Ospitalieri di Cremona
  • San Donato, Italy, 20097
    • IRCCS Policlinico San Donato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Booked for cardiac or other non-renal arteriography
• Pre-existing reduced kidney function: Serum Creatinine >= 1.3 & <= 4 mg/dl (female gender) or >= 1.5 & <= 5 mg/dl (male gender)
• Age > 18 years

Exclusion Criteria:

• GFR MDRD estimate < 15 ml/min/m2
• End-stage renal disease already on dialysis
• Known current Acute Kidney Failure with serum creatinine rise of > 0.5 mg/dl within 24 hours
• Pulmonary edema - current or within 48 hours
• Clinically relevant ascites, edema or other fluid overload
• Uncontrolled hypertension (> 165 mmHg systolic, or > 105 mmHg diastolic)
• Hemodynamically unstable patient requiring IV nitroglycerine, or IV fluid or inotropes for blood pressure support
• Emergency (unplanned) angiography
• IV contrast procedure
• Exposure to iodinated radiocontrast within 3 days prior to study
• Prior anaphylactoid reaction to contrast
• Planned administration of N-acetylcysteine
• Planned administration of dopamine, fenoldopam or mannitol
• Current pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bicarbonate; Bicarbonate solution infusion	Drug: 1/6 M (166 mEq/L) IV Sodium Bicarbonate; Bicarbonate solution; Other Names: Sodium Bicarbonate
ACTIVE_COMPARATOR: Saline; Standard volume expansion	Drug: 0.9% (154 mEq/L) IV Sodium Chloride; Saline solution; Other Names: Sodium Chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Development of contrast-induced nephropathy, CIN, defined as an increase in serum creatinine of 25% or more from pre-intervention baseline to within 48-72 hours after administration of the radiographic contrast.	48-72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Group mean change in serum creatinine	48-72 hours
Days in hospital within the week post contrast	One week
Requirement for dialysis	Two months
Atheroembolic events	Two months
Major adverse cardiovascular events	Two months
Death	Two months

Collaborators and Investigators

• Sponsor: Italian Society of Nephrology
• Collaborators: European Commission; Memorial University of Newfoundland
• Investigators: Principal Investigator: Pietro Ravani, MD, MSc, Italian Society of Nephrology; Study Chair: Brendan BJ Barrett, MD, MSc, Memorial University of Newfoundland; Study Chair: Ferruccio Conte, MD, Italian Society of Nephrology

Publications and helpful links

General Publications

• 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.
• Ravani P, Tripepi G, Pecchini P, Mallamaci F, Malberti F, Zoccali C. Urotensin II is an inverse predictor of death and fatal cardiovascular events in chronic kidney disease. Kidney Int. 2008 Jan;73(1):95-101. doi: 10.1038/sj.ki.5002565. Epub 2007 Oct 17.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (ACTUAL): July 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: October 5, 2006
• First Submitted That Met QC Criteria: October 5, 2006
• First Posted (ESTIMATE): October 6, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): December 1, 2010
• Last Update Submitted That Met QC Criteria: November 29, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Contrast Induced Nephropathy; Percutaneous coronary intervention; Saline; Cardiovascular diseases; Coronary catheterization; Acute Renal Failure; End-stage Renal Disease; Bicarbonate; Intra-arterial angiography
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: PR021676