Prevention of Serious Adverse Events Following Angiography (PRESERVE)
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Purpose
The purpose of this research study is to compare the effectiveness of intravenous isotonic sodium bicarbonate with intravenous isotonic sodium chloride and oral N-acetylcysteine with oral placebo for the prevention of serious adverse outcomes following angiographic procedures in high-risk patients.
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Renal Failure Kidney Disease Coronary Artery Disease |
Drug: IV isotonic saline Drug: IV isotonic bicarbonate Drug: N-acetylcysteine Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention |
| Official Title: | CSP #578 - Prevention of Serious Adverse Outcomes Following Angiography |
- The primary outcome will be a composite of serious, adverse, patient-centered events, including death, need for acute dialysis, or persistent decline in kidney function. [ Time Frame: Within 90 days following angiography ] [ Designated as safety issue: No ]
Death will be based on medical record and/or vital status registry documentation
Need for acute dialysis will be defined as the initiation of any modality of renal replacement (intermittent hemodialysis, peritoneal dialysis, continuous renal replacement therapy, or sustained low-efficiency dialysis)
Persistent decline in kidney function will be defined as an increase in serum creatinine of at least 50% from the baseline value collected pre-angiography to the measurement taken 90 days following the angiography.
| Estimated Enrollment: | 8680 |
| Study Start Date: | February 2013 |
| Estimated Study Completion Date: | December 2016 |
| Estimated Primary Completion Date: | March 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm 1
IV isotonic saline and oral placebo drug capsule
|
Drug: IV isotonic saline
We will administer 3 ml/kg of isotonic saline over 1 hour at an infusion rate of not less than 1 mL/kg per hour and not more than 3 mL/kg per hour prior to the angiographic procedure, 1-1.5ml/kg per hour during angiography, and 6 ml/kg of isotonic saline over 4 hours following the procedure at an infusion rate of not less than 1 mL/kg per hour and not more than 1.5 mL/kg per hour. Providers will retain discretion to administer larger volumes of isotonic saline (up to a maximum of 12 mL/kg) over durations of up to 12 hours pre and 12 hours post-procedure.
Drug: Placebo
A placebo study drug capsule will be administered orally 1 hour prior to angiography, 1 hour following the procedure, and then twice daily for the next 4 days.
|
|
Active Comparator: Arm 2
IV isotonic saline and oral N-acetylcysteine drug capsule
|
Drug: IV isotonic saline
We will administer 3 ml/kg of isotonic saline over 1 hour at an infusion rate of not less than 1 mL/kg per hour and not more than 3 mL/kg per hour prior to the angiographic procedure, 1-1.5ml/kg per hour during angiography, and 6 ml/kg of isotonic saline over 4 hours following the procedure at an infusion rate of not less than 1 mL/kg per hour and not more than 1.5 mL/kg per hour. Providers will retain discretion to administer larger volumes of isotonic saline (up to a maximum of 12 mL/kg) over durations of up to 12 hours pre and 12 hours post-procedure.
Drug: N-acetylcysteine
NAC will be administered at a dose of 1200mg orally 1 hour prior to angiography, 1 hour following the procedure, and then twice daily for the next 4 days.
Other Name: NAC
|
|
Active Comparator: Arm 3
IV isotonic bicarbonate and oral placebo drug capsule
|
Drug: IV isotonic bicarbonate
We will administer 3 ml/kg of isotonic bicarbonate over 1 hour at an infusion rate of not less than 1 mL/kg per hour and not more than 3 mL/kg per hour prior to the angiographic procedure, 1-1.5ml/kg per hour during angiography, and 6 ml/kg of isotonic bicarbonate over 4 hours following the procedure at an infusion rate of not less than 1 mL/kg per hour and not more than 1.5 mL/kg per hour. Providers will retain discretion to administer larger volumes of isotonic bicarbonate (up to a maximum of 12 mL/kg) over durations of up to 12 hours pre and 12 hours post-procedure.
Drug: Placebo
A placebo study drug capsule will be administered orally 1 hour prior to angiography, 1 hour following the procedure, and then twice daily for the next 4 days.
|
|
Active Comparator: Arm 4
IV isotonic bicarbonate and oral N-acetylcysteine drug capsule
|
Drug: IV isotonic bicarbonate
We will administer 3 ml/kg of isotonic bicarbonate over 1 hour at an infusion rate of not less than 1 mL/kg per hour and not more than 3 mL/kg per hour prior to the angiographic procedure, 1-1.5ml/kg per hour during angiography, and 6 ml/kg of isotonic bicarbonate over 4 hours following the procedure at an infusion rate of not less than 1 mL/kg per hour and not more than 1.5 mL/kg per hour. Providers will retain discretion to administer larger volumes of isotonic bicarbonate (up to a maximum of 12 mL/kg) over durations of up to 12 hours pre and 12 hours post-procedure.
Drug: N-acetylcysteine
NAC will be administered at a dose of 1200mg orally 1 hour prior to angiography, 1 hour following the procedure, and then twice daily for the next 4 days.
Other Name: NAC
|
Detailed Description:
The intravascular administration of iodinated contrast media for diagnostic imaging is a common cause of acute kidney injury (AKI) and a leading cause of iatrogenic renal disease. Contrast-induced AKI is associated with serious adverse outcomes including death, need for dialysis, prolonged hospitalization, and acceleration in the rate of progression of underlying chronic kidney disease. The benefit of IV isotonic bicarbonate compared to IV isotonic saline and of N-acetylcysteine for the prevention of contrast-induced AKI and associated adverse outcomes remains unclear. The purpose of this trial is to compare the effectiveness of IV isotonic sodium bicarbonate with IV isotonic sodium chloride and oral NAC with placebo for the prevention of serious adverse outcomes in 8,680 high-risk patients scheduled to undergo coronary or non-coronary angiography. Using a 2 x 2 factorial design, patients will be randomized to receive: 1) either peri-procedural IV isotonic sodium bicarbonate or peri-procedural IV isotonic saline and 2) either oral NAC or oral placebo prior to and for 5 days following the angiographic procedure. The primary study endpoint is a composite outcome comprised of death, need for acute dialysis, or persistent decline in kidney function within 90 days following the index angiogram.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Planned elective or urgent coronary or non-coronary angiography with iodinated contrast media in which it is anticipated that there will be an interval of 3 hours between the identification of the indication for angiography and the time of the planned procedure.
- Pre-angiography eGFR <60 ml/min/1.73 m2 with diabetes mellitus or pre-angiography eGFR <45 ml/min/1.73 m2 with or without diabetes mellitus
- Ability to provide informed consent
Exclusion Criteria:
- ESRD requiring chronic renal replacement therapy
- Stage 5 CKD (eGFR <15 mL/min/1.73 m2)
- Acute kidney injury requiring intermittent hemodialysis or continuous renal replacement therapy at the time of angiography
- Unstable baseline SCr (if known) at the time of angiography defined by an increase in SCr of 25% over the 3 days prior to angiography
Decompensated heart failure requiring any of the following therapies at the time of angiography:
- IV milrinone, amrinone, dobutamine, or nesiritide
- Isolated ultrafiltration therapy
- Intra-aortic balloon pump
- Emergent angiography procedures defined as an anticipated duration of <3 hours between the identification of the indication for angiography and the time of the planned procedure.
- Receipt of intravascular iodinated contrast within the 7 days preceding angiography
- Receipt of oral or IV NAC within the 48 hours preceding angiography
- Known allergy to N-acetylcysteine (NAC)
- Known allergy to iodinated contrast media
- Prisoner
- Age <18 years
- Pregnancy
- Ongoing participation in a concurrent interventional study
Contacts and Locations| Contact: James S Kaufman, MD | (212) 686-7500 ext 7470 | james.kaufman@va.gov |
| Contact: Danielle L Valley | danielle.valley@va.gov |
Show 45 Study Locations| Study Chair: | Steven D. Weisbord, MD MSc | VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA |
More Information
No publications provided
| Responsible Party: | Department of Veterans Affairs |
| ClinicalTrials.gov Identifier: | NCT01467466 History of Changes |
| Other Study ID Numbers: | 578, 1011387 |
| Study First Received: | October 26, 2011 |
| Last Updated: | February 20, 2013 |
| Health Authority: | United States: Federal Government United States: Food and Drug Administration |
Keywords provided by Department of Veterans Affairs:
|
renal cardiovascular kidney heart clinical trial double-blind |
multi-site trial randomized drug treatment IV solutions antioxidant |
Additional relevant MeSH terms:
|
Coronary Artery Disease Myocardial Ischemia Coronary Disease Kidney Diseases Acute Kidney Injury Renal Insufficiency Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Urologic Diseases Acetylcysteine |
N-monoacetylcystine Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Expectorants Respiratory System Agents Free Radical Scavengers Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Antidotes |
ClinicalTrials.gov processed this record on May 22, 2013