Prevention of Serious Adverse Events Following Angiography (PRESERVE)

Tracking Information
First Submitted Date ICMJE	October 26, 2011
First Posted Date ICMJE	November 8, 2011
Last Update Posted Date	January 24, 2018
Actual Study Start Date ICMJE	February 7, 2013
Actual Primary Completion Date	September 29, 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 3, 2011)	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 ]; 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.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01467466 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
Descriptive Information
Brief Title ICMJE	Prevention of Serious Adverse Events Following Angiography
Official Title ICMJE	CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)
Brief Summary	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.
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 7,680 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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
Condition ICMJE	Acute Renal Failure; Kidney Disease; Coronary Artery Disease
Intervention ICMJE	Drug: IV isotonic saline The investigators 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: IV isotonic bicarbonate The investigators 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; 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.
Study Arms	Active Comparator: Arm 1 IV isotonic saline and oral placebo drug capsule Interventions: Drug: IV isotonic saline Drug: Placebo; Active Comparator: Arm 2 IV isotonic saline and oral N-acetylcysteine drug capsule Interventions: Drug: IV isotonic saline Drug: N-acetylcysteine; Active Comparator: Arm 3 IV isotonic bicarbonate and oral placebo drug capsule Interventions: Drug: IV isotonic bicarbonate Drug: Placebo; Active Comparator: Arm 4 IV isotonic bicarbonate and oral N-acetylcysteine drug capsule Interventions: Drug: IV isotonic bicarbonate Drug: N-acetylcysteine
Publications *	Weisbord SD, Gallagher M, Jneid H, Garcia S, Cass A, Thwin SS, Conner TA, Chertow GM, Bhatt DL, Shunk K, Parikh CR, McFalls EO, Brophy M, Ferguson R, Wu H, Androsenko M, Myles J, Kaufman J, Palevsky PM; PRESERVE Trial Group. Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018 Feb 15;378(7):603-614. doi: 10.1056/NEJMoa1710933. Epub 2017 Nov 12.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 3, 2017)	5183
Original Estimated Enrollment ICMJE; (submitted: November 3, 2011)	8680
Actual Study Completion Date	October 17, 2017
Actual Primary Completion Date	September 29, 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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: Stage 5 CKD (eGFR <15 mL/min/1.73 m2); Currently receiving hemodialysis, peritoneal dialysis, continuous renal replacement therapy, or sustained low efficiency dialysis (SLED); 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 5 days preceding angiography; Receipt of oral or IV NAC within the 48 hours preceding angiography; Known allergy to N-acetylcysteine (NAC); Known anaphylactic allergy to iodinated contrast media; Prisoner; Age <18 years; Pregnancy; Ongoing participation in an unapproved concurrent interventional study
Sex/Gender	Sexes Eligible for Study: All
Ages	18 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	Australia, Malaysia, New Zealand, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01467466
Other Study ID Numbers ICMJE	578; 1011387 ( Other Grant/Funding Number: National Health and Medical Research Council )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement	Plan to Share IPD: Undecided
Responsible Party	VA Office of Research and Development
Study Sponsor ICMJE	VA Office of Research and Development
Collaborators ICMJE	The George Institute
Investigators ICMJE	Study Chair: Steven D. Weisbord, MD MSc VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
PRS Account	VA Office of Research and Development
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP