Renoprotective Effects of Fluid Prophylaxis Strategies for Contrast Induced Nephropathy (CIN)

NCT00749827 | Withdrawn Phase 4

• 1 other identifier: IIS-US-0048
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Contrast induced nephropathy (CIN) is a term applied to acute renal failure associated with intravascular injection of iodinated contrast agents typically used for cardiac angiography. CIN occurs in about 15% of those who have had cardiac angiography, with dialysis required by about 0.5% of cases. The development of CIN is associated with other adverse outcomes including major adverse cardiovascular events (MACE) and death. The mechanism underlying the association with MACE and death is unclear and it is largely unknown whether measures reducing the frequency or severity of CIN also reduce these associated adverse events. The cause of CIN in humans is not known, but many preventive therapies have been tested based on our understanding of the mechanism underlying CIN from animal models. Despite multiple studies, no one drug or therapy has been proven to consistently prevent CIN at this time. Prophylactic fluid therapy is uniformly recommended as a component of preventive approaches for CIN. However, the optimal type, dose and duration of fluid therapy remain unclear. Existing studies suggest a role for isotonic saline\[3\] or bicarbonate\[4\]. Initial use of hypotonic fluid followed by isotonic fluid might allow a more rapid and sustained increase in tubular fluid flow by suppression of ADH. This should assist in reducing tubular fluid viscosity and the potential for injury by contrast medium. The aim of this research program is to design and test strategies for the prevention of CIN in patients undergoing elective cardiac angiography or percutaneous coronary intervention (PCI). The primary purpose of this pilot study will be to determine the biological plausibility of using a hypotonic solution for CIN prophylaxis. Specific Objectives: Primary

1. 1.To compare the effects of two fluid prophylaxis strategies for CIN on urine output, urine pH, urine composition (urine metabolic profiling), a novel marker of renal injury (NGAL) and urine osmolality Secondary
2. 2.To assess the relative sensitivity of definitions of CIN based on changes in serum creatinine or cystatin C within 72 hours post contrast.
3. 3.To determine the feasibility of a future multicenter randomized trial of a hypotonic fluid prophylaxis strategy for the prevention of radiocontrast nephropathy.

Conditions

Contrast Induced Nephropathy

Keywords

Contrast Induced Nephropathy, fluid prophylaxis

Outcome Measures

Primary Outcomes (1)

• Serum creatinine, cystatin C,and urine samples for measurement of urine pH, osmolality, electrolytes and creatinine,NGAL and metabolic profiling

  SeCr and Cystatin C will be collected at baseline 6hrs, 24, and 48 -72 hrs post cath, urine at baseline, pre-cath, and 6 hours post angiography

Study Arms (2)

1

ACTIVE COMPARATOR

Intravenous sodium bicarbonate (130 mEq/L) in 4.35% dextrose at 3.5 ml/Kg over 1 hour pre-contrast, followed by the same solution intravenously at 1 ml/Kg/hr for 6 hours

Drug: Bicarbonate Hydration

2

ACTIVE COMPARATOR

Hypotonic hydration arm. Intravenous 5% dextrose in water at 3.5 ml/Kg over 1 hour pre-contrast followed by 0.9% saline intravenously at 1 ml/Kg/hr for 6 hours.

Drug: Hypotonic hydration

Interventions

Bicarbonate Hydration DRUG

Intravenous sodium bicarbonate (130 mEq/L) in 4.35% dextrose at 3.5 ml/Kg over 1 hour pre-contrast, followed by the same solution intravenously at 1 ml/Kg/hr for 6 hours. In all cases the maximum rate of fluid permitted is that for a body weight of 110 Kg. Intra-vascular low-osmolal or iso-osmolal contrast (according to operator or institution choice) will be used in the minimal dose needed to complete the required imaging. Hypotonic hydration arm. Intravenous 5% dextrose in water at 3.5 ml/Kg over 1 hour pre-contrast followed by 0.9% saline intravenously at 1 ml/Kg/hr for 6 hours.

Also known as: Sodium Bicarbonate(130 mEq/L) in 4.35% dextrose

1

Hypotonic hydration DRUG

Intravenous 5% dextrose in water at 3.5 ml/Kg over 1 hour pre-contrast followed by 0.9% saline intravenously at 1 ml/Kg/hr for 6 hours.

Also known as: Dextrose(5%) in Water

2

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Booked for cardiac angiography and/or percutaneous coronary intervention
• Pre-existing reduced kidney function (estimated GFR \< 60 mls/min/1.73m2 by MDRD equation\[18\]).
• Minimum age 20 years
• Able to return to the study site for followup blood work.

You may not qualify if:

• Estimated GFR \< 15 mls/min/1.73m2 by MDRD equation
• Already on dialysis
• Known current acute kidney failure with serum creatinine rise of \> 45 mol/L within 24 hours
• Pulmonary edema - current or within 48 hours
• Clinically significant ascites, edema or other fluid overload
• Uncontrolled hypertension (\> 165 mmHg systolic, or \> 105 mmHg diastolic)
• Unstable patient requiring IV nitroglycerine, or IV fluid or inotropes for BP support
• Emergency angiography
• Planned primary PCI for acute coronary syndrome or myocardial infarction
• Exposure to iodinated radiocontrast within 3 days prior to study
• Prior anaphylactoid reaction to contrast
• Planned administration of N-acetyl-cysteine, dopamine, fenoldopam or mannitol

Sponsors & Collaborators

• Memorial University of Newfoundland: lead
• University of Alberta: collaborator

Study Sites (2)

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3, Canada

Location

Memorial University of Newfoundland

St. John's, Newfoundland and Labrador, A1S 1B9, Canada

Location

MeSH Terms

Interventions

Glucose; Water

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Brendan J. Barrett, MD M.Sc.

  Memorial University of Newfoundland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 9, 2008
• Last Updated: April 20, 2016

Record last verified: 2016-04

Locations

CA (2)