Study Question: Does the use of sodium bicarbonate or acetylcysteine affect outcomes after angiography
Trial Summarized by: Hajra Munawar, MD; Hasan Shafiq, MD
Contribution to literature
This trial revealed that the patients with impaired kidney function who were undergoing angiography showed no benefit of periprocedural IV isotonic sodium bicarbonate over IV isotonic sodium chloride or of oral acetylcysteine over placebo with respect to major adverse kidney events, death, or acute kidney injury.
Description of the trail
The goal of this trial was to compare renal complications in patients who were scheduled for angiography to receive IV 1.26% sodium bicarbonate or IV 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo, and assess the overall difference among the composite of death, need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine levels at 90 days.
It was a double-blinded, placebo and comparator-drug controlled, randomized trial sponsored by U.S Department of Veterans Affairs Cooperative Studies Program and George Institute for Global Health from February 2013 through March 2017, patients were enrolled at 53 medical centers in the United states (35 veterans Affairs sites),Australia(13 sites),Malaysia(3 sites) and New Zealand(2 sites).
Patients were randomly assigned to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and oral acetylcysteine capsule or matched placebo capsules. The administration of trial IV fluids was based on protocol-specified ranges: 1 to 3 ml/kg/hr during a period of 1 to 12 hours for a total of 3 to 12 ml/kg/hr before angiography, 1 to 1.5 ml/kg/hr during angiography, 1 to 3ml/kg/hr during the period of 2 to 12 hrs for total volume of 6 to 12 ml/kg after angiography.
From each patient, a blood sample collected before the initiation of trial intravenous fluids and at 3 to 5 days and 90 t0 104 days after angiography. Urine samples are collected for local measurement of albumin and creatinine at the time of angiography and for PH measurement 2 to 4 hours after angiography.
- Total number of patients: 5177(4441 at Veterans Affairs sites and 736 at George Institute sites) underwent randomization after randomization 184 patients were withdrawn, which resulted in 4993 patients for primary analysis.
- Duration of follow up: from February through March 2017
- Mean patient age: 69 year
- Percentage male: 93.6%
- Percentage diabetics:80.9%
- Median serum Cr:1.5mg/dl
- Median eGFR:50.2 ml per min per 1.73m2
- Median volume of contrast material administered was 85ml.
- Median volume of trial IV fluid administered was 344ml before,114ml during,570ml after angiography.
- After angiography mean urine PH was 6.7 +/- 0.8 in the sodium bicarbonate group and 6 +/_ 0.8 in sodium chloride group (p=<.001)
Modified intention to treat analysis was used that included all the patients who had undergone randomization and who had received the assigned trial interventions, regardless of whether they had undergone angiography. The comparison was done using the t-test for normally distributed continuous variables, the Wilcoxon rank-sum test for variables without a normal distribution and the chi-square test for categorical variables. To test the interaction between sodium bicarbonate and acetylcysteine, a multivariable logistic regression model was used.
- Patients who were scheduled to undergo coronary or noncoronary angiography
- Patients who had an eGFR of 55 -44.9ml per min per 1.73 m2
- Patients with diabetes mellitus and e GFR 45 -59.9 ml per minute per 1.73 m2
Patients who were undergoing emergency angiography
Patients with unstable baseline levels of blood creatinine( increase or decrease of >25% within 3 days before angiography)
- The primary composite endpoint occurred in 110 patients in the sodium bicarbonate group as compared with 116 patients in the sodium chloride groups(odds ratio: 0.93; 95% CI, 0.72 to 1.22 ;P =0.62) and in 114 patients in the acetylcysteine group as compared with 112 in the placebo group (odds ratio:1.02; 95% CI ,0.78 – 1.33 ;P = 0.88).There were no significant differences in the primary composite end point in the comparison of treatment combination groups.
- There was also no significant difference in the need for dialysis, or a persistent increase of at least 50% from baseline in serum creatinine level at 90 to 140 days after angiography in the comparison of sodium bicarbonate with sodium chloride or in the combinations of acetylcysteine with placebo.
- There was a significantly higher risk of the primary composite endpoint in sodium bicarbonate as compared to sodium chloride in patients who have undergone noncoronary angiography.(odds ratio,3.19;95%CI ,1.03 to 9.94)
- Contrast associated acute kidney injury occurred in 239 patients in the sodium bicarbonate group as compared with 206 in the sodium chloride group (odds ratio ,1.16;CI,0.96-1.41 ;P=0.13)and in 228 patients in the acetylcysteine group as compared with 217 in the placebo group (odds ratio ,1.06;95%CI, 0.87 -1.28; P =0.58)
- There were no significant differences in the incidence of, death within 90 days; dialysis of any kind within 90 days; confirmed persistent kidney impairment at 90 to 104 days; hospitalization with ACS, heart failure or stroke within 90 days; and hospitalization for any cause within 90 days.
In patients with chronic kidney disease who underwent angiography, no benefit of IV sodium bicarbonate over IV sodium chloride or of oral acetylcysteine was seen compared to placebo. Unlike most previous trials in which primary endpoint was a small increase in the blood creatinine level occurring within days after the IV contrast, the primary endpoint in this trial was a composite of serious adverse outcomes such as mortality, need for dialysis and worsening of renal function.
Steven D. Weisbord, M.DMartin Gallagher, M.D., Ph.D., Hani Jneid, M.D., Santiago Garcia, M.D., Alan Cass, M.D., Ph.D., Soe-Soe Thwin, Ph.D., Todd A. Conner, Pharm.D., Glenn M. Chertow, M.D., M.P.H., Deepak L. Bhatt, M.D., M.P.H., Kendrick Shunk, M.D., Ph.D., Chirag R. Parikh, M.D., Ph.D., Edward O. McFalls, M.D., PhD., et al., for the PRESERVE Trial Group*