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      Calcium-containing versus calcium-free replacement solution in regional citrate anticoagulation for continuous renal replacement therapy: a randomized controlled trial

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          Abstract

          Background:

          A simplified protocol for regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without continuous calcium infusion, is more efficient for use in continuous renal replacement therapy (CRRT). We aim to design a randomized clinical trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solutions in CRRT with RCA.

          Methods:

          Of the 64 patients receiving RCA-based postdilution continuous venovenous hemodiafiltration (CVVHDF) enrolled from 2017 to 2019 in West China Hospital of Sichuan University, 35 patients were randomized to the calcium-containing group and 29 to the calcium-free replacement solution group. The primary endpoint was circuit lifespan and Kaplan–Meier survival analysis was performed. Secondary endpoints included hospital mortality, kidney function recovery rate, and complications. The amount of 4% trisodium citrate solution infusion was recorded. Serum and effluent total (tCa) and ionized (iCa) calcium concentrations were measured during CVVHDF.

          Results:

          A total of 149 circuits (82 in the calcium-containing group and 67 in the calcium-free group) and 7609 circuit hours (4335 h vs. 3274 h) were included. The mean circuit lifespan was 58.1 h (95% CI 53.8–62.4 h) in the calcium-containing group vs. 55.3 h (95% CI 49.7–60.9 h, log rank P = 0.89) in the calcium-free group. The serum tCa and iCa concentrations were slightly lower in the calcium-containing group during CRRT, whereas the postfilter iCa concentration was lower in the calcium-free group. Moreover, the mean amounts of 4% trisodium citrate solution infusion were not significantly different between the groups (171.1 ± 15.9 mL/h vs. 169.0 ± 15.1 mL/h, P = 0.49). The mortality (14/35 [40%] vs. 13/29 [45%], P = 0.70) and kidney function recovery rates of AKI patients (19/26, 73% vs. 14/24, 58%, P = 0.27) were comparable between the calcium-containing and calcium-free group during hospitalization, respectively. Six (three in each group) patients showed signs of citrate accumulation in this study.

          Conclusions:

          When compared with calcium-free replacement solution, RCA-based CVVHDF with calcium-containing replacement solution had a similar circuit lifespan, hospital mortality and kidney outcome. Since the calcium-containing solution obviates the need for a separate venous catheter and a large dose of intravenous calcium solution preparation for continuous calcium supplementation, it is more convenient to be applied in RCA-CRRT practice.

          Registration:

          Chinese Clinical Trial Registry ( www.chictr.org.cn , ChiCTR-IPR-17012629)

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          Most cited references32

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          Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury.

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            Trials to assess equivalence: the importance of rigorous methods.

            The aim of an equivalence trial is to show the therapeutic equivalence of two treatments, usually a new drug under development and an existing drug for the same disease used as a standard active comparator. Unfortunately the principles that govern the design, conduct, and analysis of equivalence trials are not as well understood as they should be. Consequently such trials often include too few patients or have intrinsic design biases which tend towards the conclusion of no difference. In addition the application of hypothesis testing in analysing and interpreting data from such trials sometimes compounds the drawing of inappropriate conclusions, and the inclusion and exclusion of patients from analysis may be poorly managed. The design of equivalence trials should mirror that of earlier successful trials of the active comparator as closely as possible. Patient losses and other deviations from the protocol should be minimised; analysis strategies to deal with unavoidable problems should not centre on an "intention to treat" analysis but should seek to show the similarity of results from a range of approaches. Analysis should be based on confidence intervals, and this also carries implications for the estimation of the required numbers of patients at the design stage.
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              Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial

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                Author and article information

                Journal
                Chin Med J (Engl)
                Chin Med J (Engl)
                CM9
                Chinese Medical Journal
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0366-6999
                2542-5641
                20 October 2022
                09 December 2022
                : 135
                : 20
                : 2478-2487
                Affiliations
                Department of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
                Author notes
                Correspondence to: Dr. Ling Zhang, Department of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China E-Mail: zhanglinglzy@ 123456163.com
                Article
                CMJ-2022-488
                10.1097/CM9.0000000000002369
                9945286
                36583864
                e863e0d1-88fa-43b6-b4b3-a4ef842b3c0e
                Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 22 February 2022
                Categories
                Original Articles
                Custom metadata
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                anticoagulant agent,circuit lifespan,continuous renal replacement therapy,dialysis solutions,randomized controlled trial,sodium citrate

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