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Fluid Chloride and AKI in Cardiopulmonary Bypass

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ClinicalTrials.gov Identifier: NCT02668952
Recruitment Status : Completed
First Posted : January 29, 2016
Results First Posted : March 19, 2018
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Neal Gerstein, University of New Mexico

Tracking Information
First Submitted Date  ICMJE January 20, 2016
First Posted Date  ICMJE January 29, 2016
Results First Submitted Date  ICMJE February 15, 2018
Results First Posted Date  ICMJE March 19, 2018
Last Update Posted Date May 14, 2018
Actual Study Start Date  ICMJE January 2016
Actual Primary Completion Date February 4, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 15, 2018)
Change in [TIMP2]*[IGFBP7] Biomarker [ Time Frame: Baseline and postoperatively at 24 hours ]
The difference in the [TIMP2]*[IGFBP7] biomarker between the preoperative value and a repeated measurement at 24 hours postoperatively. Positive values represent increase; negative values represent decrease
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2016)
Change in [TIMP2]*[IGFBP7] Biomarker [ Time Frame: Baseline and postoperatively at 24 hours ]
The difference in the [TIMP2]*[IGFBP7] biomarker between the preoperative value and a repeated measurement at 24 hours postoperatively
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 15, 2018)
  • Serum Creatinine Level at 24 Hours [ Time Frame: 1 day ]
    Serum creatinine measurement at 24 hours
  • Serum Chloride Level at 24 Hours [ Time Frame: 1 day ]
    Serum chloride ion measurement at 24 hours postoperatively
  • Proportion of Patients With Need for Dialysis [ Time Frame: One week ]
    Clinically-determined need for dialysis prior to discharge from hospital
  • Postoperative Arterial pH [ Time Frame: One day ]
    Arterial pH, measured 24 hours after surgery
  • Serum Creatinine Level at 48 Hours [ Time Frame: 2 days ]
    Serum creatinine level 48 hours postoperatively
  • Serum Chloride at 48 Hours [ Time Frame: 2 days ]
    Serum chloride measurement at 48 hours postoperatively
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2016)
  • Serum creatinine level [ Time Frame: Baseline and postoperatively at 24 and 48 hours ]
    Serum creatinine measurement at baseline, and postoperatively at 24 and 48 hours
  • Serum chloride level [ Time Frame: Baseline and postoperatively at 24 and 48 hours ]
    Serum chloride ion measurement at baseline, and postoperatively at 24 and 48 hours
  • Proportion of Patients With Need for Dialysis [ Time Frame: One week ]
    Clinically-determined need for dialysis prior to discharge from hospital
  • Postoperative Arterial pH [ Time Frame: One day ]
    Arterial pH, measured 24 hours after surgery
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fluid Chloride and AKI in Cardiopulmonary Bypass
Official Title  ICMJE The Impact of Low Chloride Containing Fluids on Acute Kidney Injury After Cardiopulmonary Bypass as Assayed by Urinary [TIMP2*IGFBP7]
Brief Summary Acute kidney injury (AKI) is a potential complication of cardiac surgery. In animal models, excess exogenous Cl- ion in the bloodstream is associated with AKI. Normal saline IV fluid has higher levels of Cl- ion than the blood usually carries. An alternative IV fluid sold under the name Isolyte has lower Cl- ion levels. There is no literature comparing AKI outcomes in cardiac patients between patients receiving normal saline vs. Isolyte. The investigators propose to recruit and randomize 30 trial-completing cardiac surgery patients (up to 40 enrolled) into 2 study arms and compare renal outcomes.
Detailed Description

Acute kidney injury (AKI) is a potential complication for patients undergoing cardiac surgery. AKI in post-cardiac surgery patients is associated with adverse outcomes, such as prolonged intensive care and hospital stay, diminished quality of life, increased long-term mortality, and an increased risk of chronic kidney disease requiring dialysis. The mortality in cardiac surgery patients with AKI severe enough to require renal replacement therapy (RRT) can be as high as 60%. One of the putative agents associated with AKI in animal models receiving crystalloid fluids for resuscitative interventions is excess exogenous chloride ion (Cl-). As compared to non-Cl- containing solutions in animal models, excess Cl- appears to lead to a hyperchloremic metabolic acidosis, increased renal vascular resistance, reduced renal blood flow, and reduced glomerular filtration rate - all of which are injurious to kidney function.

Historically, one of the most common balanced salt-solutions used in adult cardiac surgery has been 0.9% normal saline (NS), a crystalloid solution with 154 mmol/L of Cl-. This is much higher than physiologic plasma levels of 103 mmol/L. Isolyte, a less commonly used crystalloid solution, is much closer to physiologic levels at 98 mmol/L Cl-. In the context of cardiac surgery, there is no literature expressly comparing the effects of balanced crystalloid solution such as Isolyte versus NS on AKI incidence. There is a single trial examining a low-Cl- containing colloid solution in cardiac surgery that found less metabolic acidosis; however, AKI or markers of AKI were not measured outcomes in that lone trial, so it is not known whether low Cl- solution will have any effect on AKI risk in humans.

AKI results from a series of extremely complex cellular and molecular pathways involving endothelial, epithelial, inflammatory, and interstitial cells. The gold standard for identification and classification of AKI is dependent on serial serum creatinine (Scr) measurements, but this measurement can be unreliable during acute changes in kidney function. Recent studies have shown that tissue inhibitor of metalloproteinase (TIMP-2) performs better than existing markers for predicting the development of moderate or severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage 2 or 3) within 12 hours of sample collection. To further enhance the sensitivity of utilizing TIMP-2, the investigators plan on also measuring urinary insulin-like growth factor-binding protein 7 (IGFBP7). Along with TIMP-2, IGFBP7 is also an inducer of G1 cell cycle arrest, a key mechanism implicated in AKI.

This study will utilize the urinary [TIMP-2]*[IGFBP7] multiplicative product as a composite biomarker index to investigate the impact of intraoperative infusion of NS versus Isolyte on post-cardiac surgery renal function. This biomarker should identify patients at risk of imminent (within 12 hours) AKI KDIGO criteria.

Patients presenting for cardiac surgery are already quite ill often with multiple comorbidities. Acute kidney injury in this population is associated with significant morbidity and mortality. The available literature indicates that a fairly simple intervention could plausibly reduce the incidence of AKI, but it has not yet been examined in humans. Generating an evidence basis for it will substantially improve the safety of patients who need cardiac surgery. This intervention to reduce AKI may also then be applied to the broader non-cardiac surgery population as well.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Acute Kidney Injury
Intervention  ICMJE
  • Drug: 0.9% Normal Saline (0.9% Sodium Chloride) injection
  • Drug: Isolyte S injection
Study Arms  ICMJE
  • Active Comparator: Normal Saline group
    0.9% Normal Saline (0.9% Sodium Chloride) injection intravenously as needed. The amount administered (dosage, frequency, and duration) will be left to the clinical judgment of the attending physicians, and will follow usual patterns of use in cardiac surgery patients.
    Intervention: Drug: 0.9% Normal Saline (0.9% Sodium Chloride) injection
  • Experimental: Isolyte group
    Isolyte S (B Braun, Irvine CA) injection intravenously as needed. The amount administered (dosage, frequency, and duration) will be left to the clinical judgment of the attending physicians, and will follow usual patterns of use in cardiac surgery patients. Isolyte S is a prepackaged solution containing sodium chloride 0.53%, sodium gluconate 0.5%, sodium acetate trihydrate 0.37%, potassium chloride 0.037%, and magnesium chloride hexahydrate 0.03% w/v.
    Intervention: Drug: Isolyte S injection
Publications * Not Provided

*   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: January 26, 2016)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2018
Actual Primary Completion Date February 4, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Planned on- or off-pump cardiac surgery including: bypass grafting, valvular procedures, congenital defect correction, and thoracic aortic procedures or a combination of these procedures

Exclusion Criteria:

  • Emergency surgery
  • Pregnancy
  • Previous renal transplantation
  • Documented moderate to severe acute kidney injury prior to enrollment (e.g. RIFLE-I or RIFLE-F/KDIGO stage 2 or 3)
  • Patients already receiving dialysis (acute or chronic) or in imminent need of dialysis at time of enrollment
  • Chronic kidney disease without baseline serum creatinine value obtained within 6 months of enrollment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02668952
Other Study ID Numbers  ICMJE 15-572
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Upon publication of study results, qualified researchers may contact the PI for the deidentified dataset.
Responsible Party Neal Gerstein, University of New Mexico
Study Sponsor  ICMJE University of New Mexico
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Neal S Gerstein, MD University of New Mexico
PRS Account University of New Mexico
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP