Prevention of Serious Adverse Events Following Angiography - Full Text View

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 Intervention Model: Factorial Assignment Masking: Participant, Investigator Primary Purpose: Prevention
Official Title:	CSP #578 - Prevention of Serious Adverse Events Following Angiography (PRESERVE)

Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:

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.


Estimated Enrollment:	7680
Actual Study Start Date:	February 7, 2013
Estimated Study Completion Date:	September 2017
Estimated Primary Completion Date:	September 2017 (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 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: 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 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: 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 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: 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 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

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01467466

Show 54 Study Locations

Sponsors and Collaborators

VA Office of Research and Development

The George Institute

Investigators


Study Chair:	Steven D. Weisbord, MD MSc	VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

More Information


Responsible Party:	VA Office of Research and Development
ClinicalTrials.gov Identifier:	NCT01467466 History of Changes
Other Study ID Numbers:	578 1011387 ( Other Grant/Funding Number: National Health and Medical Research Council )
Study First Received:	October 26, 2011
Last Updated:	April 17, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by VA Office of Research and Development:


renal cardiovascular kidney heart clinical trial double-blind	multi-site trial randomized drug treatment IV solutions antioxidant

Additional relevant MeSH terms:


Kidney Diseases Coronary Artery Disease Myocardial Ischemia Coronary Disease Renal Insufficiency Acute Kidney Injury Urologic Diseases Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Polystyrene sulfonic acid Acetylcysteine	N-monoacetylcystine Chelating Agents Sequestering Agents Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Expectorants Respiratory System Agents Free Radical Scavengers Antioxidants Protective Agents Physiological Effects of Drugs Antidotes

ClinicalTrials.gov processed this record on July 17, 2017

Prevention of Serious Adverse Events Following Angiography (PRESERVE)