Renoprotective Effects of Fluid Prophylaxis Strategies for Contrast Induced Nephropathy (CIN) (CIN)
|ClinicalTrials.gov Identifier: NCT00749827|
Recruitment Status : Withdrawn (No funding received)
First Posted : September 9, 2008
Last Update Posted : April 20, 2016
|First Submitted Date ICMJE||September 5, 2008|
|First Posted Date ICMJE||September 9, 2008|
|Last Update Posted Date||April 20, 2016|
|Study Start Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Serum creatinine, cystatin C,and urine samples for measurement of urine pH, osmolality, electrolytes and creatinine,NGAL and metabolic profiling [ Time Frame: 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 ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00749827 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Renoprotective Effects of Fluid Prophylaxis Strategies for Contrast Induced Nephropathy (CIN)|
|Official Title ICMJE||Exploring the Renoprotective Effects of Fluid Prophylaxis Strategies for Contrast Induced Nephropathy|
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 or bicarbonate. 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.
Study Design We propose a pilot randomized trial evaluating the type of fluid chosen for CIN prophylaxis. This study will be conducted at the Health Sciences Centre, St. John's, and the University of Alberta Hospital, Edmonton.
Bicarbonate hydration arm. Intravenous sodium bicarbonate (130 mEq per L) in 4.35% dextrose at 3.5 ml per Kg over 1 hour pre-contrast, followed by the same solution intravenously at 1 ml/Kg/hr for 6 hours.
Hypotonic hydration arm. Intravenous 5% dextrose in water at 3.5 ml per Kg over 1 hour pre-contrast followed by 0.9% saline intravenously at 1 ml per Kg per 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.
Patient population The patient population for this study will be limited to urban dwellers who meet the following inclusion and exclusion criteria. Our rationale for limiting this study to urban dwellers is that blood and urine samples for NGAL need to be frozen at -70 for shipping, therefore these tests will need to be done at the sites of storage and not in peripheral labs.
Duration of Treatment and Follow up Active treatment is limited to the hours while the patient is in the cardiac catheterization laboratory. Patients will be followed up to 7 days post intervention. They will be asked to provide urine and/or blood samples collected at baseline, pre-catheterization, 2 6, 24, and 48-72 hours post-angiography. They will be followed up by telephone at 7 days post intervention to determine if they experienced any adverse events related to the procedure or the intervention.
Measures Baseline Information Baseline measures will include demographic information, comorbidity, location, and indications for cardiac procedure, type of procedure to be performed. Detailed information about the angiographic procedure will be recorded including type and volume of parenteral contrast used. In addition accurate information regarding baseline blood pressure, use of medications (specifically ACE inhibitors, angiotensin receptor blockers, NSAIDS, and diuretics) will be recorded as well as an evaluation of known risk factors for CIN.
Outcome Measures Blood will be collected for measurement of serum creatinine and cystatin C at baseline just prior to fluid administration, and at 6, 24 and 48-72 hours post-angiography. Urine samples for measurement of urine pH, osmolality, electrolytes and creatinine, and NGAL as well as metabolic profiling will be collected on all patients at baseline, pre cardiac catheterization, 6 hours postcardiac catheterization, at the end of the hydration period. As the majority of these patients will not have indwelling urinary catheters, the urine samples will be collected as close to these time points as possible. A table of sample collection timepoints is appended to this application. Assays will be performed on stored samples at a single laboratory to ensure assay standardization between sites. Duration of hospitalization (if any) will be determined by review of records.
Data collection Identification of potential participants is feasible by review of data collected for pre-admission purposes at each site's catheterization laboratory. Study investigators will work collaboratively with the catheterization labs to identify and screen potential participants. Following introduction by clinical staff, potential participants will be approached by study nurses at each site, either on the day of or the day prior to cardiac angiography. The study nurses will obtain consent, collect baseline information and blood and urine specimens, and contact the local investigator for randomization. Once each patient has been randomized the study nurse will arrange for administration of the study therapies and provide the patient with requisitions for follow up blood work. The study investigator will contact the patients either in person if hospitalized or by phone if discharged post procedure and remind them about specimen collections at each time point.
Sample Size This study is exploratory in nature and therefore not powered to a specific endpoint. Previous studies in this area have demonstrated positive results with sample sizes in the order of 50 -100 subjects. We plan to enroll 100 patients in this study.
Statistical Analysis Analysis will be by intention to treat. P values <0.05 will be considered statistically significant. Given that this is a pilot study there will be no interim analysis.
Data management Dr. Barrett and Dr. Pannu will oversee the data management for this study. Blood and urine will be collected and stored at -70C locally at both participating centers, which each have appropriate storage facilities
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
|Condition ICMJE||Contrast Induced Nephropathy|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||20 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Canada|
|Removed Location Countries|
|NCT Number ICMJE||NCT00749827|
|Other Study ID Numbers ICMJE||IIS-US-0048|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||
|Responsible Party||Brendan Barrett, Memorial University of Newfoundland|
|Study Sponsor ICMJE||Memorial University of Newfoundland|
|Collaborators ICMJE||University of Alberta|
|PRS Account||Memorial University of Newfoundland|
|Verification Date||April 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP