The Kompas Trial: Sodium Bicarbonate Prehydration in Adults with CKD Prior to Contrast-Enhanced CT

Background: Most guidelines recommend prehydration prior to iodine-based contrast media to prevent postcontrast acute kidney injury (PC-AKI) in patients with CKD.  There is, however, a lack of evidence for the effectiveness of this as well as the potential adverse effects from the hydration itself (i.e. congestive heart failure exacerbation). We have covered the AMACING trial on REBEL EM which was a randomized clinical trial evaluating prehydration with 0.9% normal saline vs no prehydration in patients with estimated glomerlular filtration rates of 30 – 59mL/min/1.73m².  In that study there was no difference in their primary outcome of contrast induced nephropathy (now called postcontrast acute kidney injury – PC-AKI) at 2 – 6 days after IV contrast (2.7% with prehydration vs 2.6% without prehydration). The trial we are are covering today, the Kompas trial, directly compared prehydration with sodium bicarbonate vs no prehydration prior to non-emergent intravenous contrast-enhanced CT in patients with CKD stage 3.

Paper: Tirnal RJ et al. Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kindey Injury in Adults with Chronic Kidney Disease: The Kompas Randomized Clinical Trial. JAMA Intern Med 2020. PMID: 32065601

Clinical Question: Is it safe to omit prophylactic prehydration with sodium bicarbonate prior to iodine-based contrast media administration in patients with stage 3 CKD?

What They Did:

• Multicenter, open-label, noninferiority, randomized clinical trial conducted at 6 hospitals in the Netherlands
• The non-inferiority margin of the primary outcome was set at <10% increase in serum creatinine level
• Patients were randomized to receive:
  • No prehydration
  • Prehydration with 250mL of 1.4% sodium bicarbonate administered in a 1hr infusion

Outcomes:

• Primary: Mean relative increase (percentage) in serum creatinine level 2 to 5 days after contrast administration compared with baseline (noninferiority margin <10% increase in serum creatinine level)
• Secondary:
  • Incidence of PC-AKI 2 to 5 days after contrast administration (Defined as an increase in creatinine level greater than 25% or greater than 0.5mg/dL) [To convert to micromoles/L, multiply by 88.4]
  • Mean relative increase in creatinine level 7 to 14 days after contrast administration
  • Recovery of renal function in patients with PC-AKI after 2 months
  • Incidence of acute heart failure
  • Incidence of renal failure requiring dialysis
  • Health care costs

Inclusion:

• Estimated glomerular filtration rate (eGFR) of 30 to 44mL/min/1.73m² (CKD stage 3B)
• eGFR of 45 to 59mL/min/1.73m² (CKD stage 3A) and:
  • Presence of diabetes mellitus OR
  • At least wo of the following risk factors:
    • Peripheral artery disease
    • Congestive Heart Failure
    • >75 years of age
    • Anemia
    • Contrast volume >150mL
    • Use of nephrotoxic medications (i.e. diuretics, NSAIDs, cyclosporin, tacrolimus, antiviral medication, amphotericin B, aminoglycosides, cisplatin, vancomycin)

Exclusion:

• eGFR<30mL/min/1.73m²
• <18 years of age
• Pregnancy
• Known allergy to contrast media
• Kidney transplant <3 years prior
• Hemodynamic instability
• Planned contrast administration 7 days prior or 5 days after IV contrast enhanced CT

Results:

• 554 patients randomized
  • 523 patients included in the intention-to-treat analysis
  • 523 patients with stage 3 CKD
    • No prehydration = 262 pts
    • Sodium Bicarbonate prehydration = 261
    • Analysis of the primary outcome was available in 505 pts (96.6%)
  • Mean relative increase in creatinine level 2 to 5 days after contrast administration compared to baseline (Primary Outcome):
    • No prehydration: 3.0%
    • Sodium Bicarbonate prehydration: 3.5%
    • Mean difference 0.5; 95% CI -1.3 to 2.3; p <0.001 for noninferiority
  • Postcontrast acute kidney injury occurred in 11 patients (2.1%):
    • No prehydration: 7/262 (2.7%)
    • Sodium Bicarbonate prehydration: 4/261 (1.5%)
    • RR 1.7; 95% CI 0.5 to 5.9; p = 0.36
    • Renal function reassessed at 2 months after CT in 8/11 patients
      • 5 pts renal function completely recovered
      • 3 pts renal function deterioration persisted (mean decrease eGFR 3mL/min/1.73m²)
    • No patients developed heart failure or required dialysis
    • Mean hydration costs:
      • No prehydration: $0/patient
      • Sodium Bicarbonate prehydration: $143.94/patient
      • P <0.001

Strengths:                    

• 1^st RCT to directly compare no prehydration with sodium bicarbonate prehydration prior to IV contrast enhanced CT
• Randomization well done
• Multicenter study increasing external validity
• Few exclusion criteria
• Follow up and tracking of final outcomes was excellent
• Dose and volume of sodium bicarbonate was based on previous randomized clinical trials that demonstrated prehydration using 250Ml of sodium bicarbonate was noninferior to saline hydration prior to and following contrast administration in patients with CKD
• In patients with missing baseline creatinine levels, the most recent value was used with a maximum duration of 1 month prior to CT
• Patients were fairly balanced between groups
• There were minimal protocol violations (23 patients – 4.4%) and very few patients missing baseline creatinine levels (29 patients – 5.5%)
• Evaluated health care costs including evaluation of expenses in the 2 months following randomization 

Limitations:

• Study only evaluated patients undergoing IV contrast enhanced CTs. Therefore, results cannot be extrapolated to angiography with intra-arterial contrast administrations
• Study also only evaluated patients undergoing elective CTs. Therefore, results cannot be extrapolated to patients requiring emergent/urgent CTs (i.e. ED population)
• Although for feasibility reasons, the primary outcome of relative increase in serum creatinine level is a lab-oriented outcome and not a patient oriented outcome
• Adverse events were rare in this study and would require a larger study to evaluate them
• A non-inferiority of 10% is likely too large a number given only a 3% change was seen in this study.

Discussion:

• This was an un-blinded study, but the outcome was based on an objective lab value and therefore should not have altered the results of the study
• Most likely doesn’t matter trying to prevent a disease that doesn’t have any patient centered harm (i.e. increase in creatinine)
• The authors estimate the hospital costs per patient between randomization and 2 months of follow up:
  • No prehydration: $1386.92
  • Prehydration: $1467.26
  • Although this was not statistically significant, with the number of CT scans that are done over the course of a month or year, this is not an insignificant amount of money

Author Conclusion: “Among patients with stage 3 CKD undergoing contrast-enhanced computed tomography, withholding prehydration did not compromise patient safety.  The findings of this study support the option of not giving prehydration a safe and cost-efficient measure.”

Clinical Take Home Point: There is no benefit of fluid expansion with sodium bicarbonate prehydration vs no prehydration in patients with stage 3 CKD requiring elective IV contrast enhanced CTs.  In addition, prehydration is accompanied with significant health care costs and although not shown in this trial could potentially increase adverse effects.

References:

1. Tirnal RJ et al. Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kindey Injury in Adults with Chronic Kidney Disease: The Kompas Randomized Clinical Trial. JAMA Intern Med 2020. PMID: 32065601

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)