Clinical trial NCT04865510: Citrate Versus Heparin in Continuous Renal Replacement Therapy :
Official title: Citrate Versus Heparin in Continuous Renal Replacement Therapy : Effect on Cardiovascular System and Clot Circuit in Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Kidney Injury
Citrate
Cytokines
Hemodynamic Responses
Lead sponsor: Bangkok Metropolitan Administration Medical College and Vajira Hospital
Sponsor class: OTHER_GOV
Collaborators: name: King Chulalongkorn Memorial Hospital
name: Chiang Mai University
name: Department of Medicine, Somdech Phra Pinklao Hospital, Bangkok, Thailand.
First posted: 2021-04-29
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This study is a prospective,multicenter, open-label randomized trial
Primary purpose: TREATMENT

Brief summary: This study is a prospective, multicenter, open-label randomized trial comparing regional citrate anticoagulation (RCA) with heparin-free protocol. The function mode was continuous venovenous hemodiafiltration (CVVHDF) in post-dilution mode. The investigators measured hemodynamic changes at certain time points after starting CRRT (0, 6, 12, 24, 48, 72 hr).Levels of inflammatory cytokine (IL-1β, IL-6, IL-8, IL-10 and TNF-ɑ) were measured at day 1 and day 3

Detailed description: Twenty patients were randomized into heparin group and 11 patients were in citrate group. The cardiac performance were not significantly different between 2 groups at every time point. The inflammatory cytokines declined similarly in both treatment arms. The maximum filter survivial time was longer in a RCA group but not reach statistically significant (44.64±26.56 hr vs p=0.693 in citrate and heparin free group respectively).There was no serious side effects dung both treatment arm even in the group of liver dysfunction patients.

Eligibility criteria: Inclusion Criteria:

* need for CRRT,
* no contraindication to CRRT

Exclusion Criteria:

* patients with previous history of chronic kidney disease (CKD) (baseline serum creatinine \> 2 mg/dL (male) or \> 1.5 mg/dL (female)
* history of renal transplantation
* known pregnancy
* previous dialysis within 30 days
* severe liver disease
* end stage heart disease or untreatable malignancy
* moribund patients with expected survival less than 30 days
* previous use of heparin or other anticoagulant, antiplatelet within 7 day except use for deep vein thrombosis
* active bleeding at the time of enrollment and/or severe coagulopathy
* receiving blood or blood components prior to enrollment
* hemoglobin less than 7.5 g/dL and/or platelet count less than 100,000/mm3
* previous underlying clotting disorders such as hypercoagulable state
* severe malnutrition (Body mass index (BMI ) less than 18)
* underwent CRRT for other reasons besides acute kidney injury (AKI)

Primary outcomes:
measure: Cardiac output
timeFrame: 72 hour
measure: Cardiac index
timeFrame: 72 hour
measure: Systemic vascular resistance
timeFrame: 72 hour
measure: Systemic vascular resistance index
timeFrame: 72 hour
Secondary outcomes:
measure: Filter life span
timeFrame: through study completion,an aveage of 72 hours
measure: Changes of IL-1β
timeFrame: day 1,day 3
measure: Changes of IL-6
timeFrame: day 1,day 3
measure: Changes of IL-8
timeFrame: day 1,day 3
measure: Changes of IL-10
timeFrame: day 1,day 3
measure: Changes of TNF-ɑ
timeFrame: day 1,day 3
measure: Mortality
timeFrame: 28 day
measure: Renal survival
timeFrame: 28 day
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Faculty of Medicine ,Vajira hospital,Navamindradhiraj University
Study officials:
affiliation: Renal unit,Faculty of Medicine,Vajira Hospital,Navamindradhiraj University
name: Thananda Trakarnvanich, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy--heparin or citrate? Crit Care. 2011 Jan 24;15(1):202. doi: 10.1186/cc9358.
citation: Gatward JJ, Gibbon GJ, Wrathall G, Padkin A. Renal replacement therapy for acute renal failure: a survey of practice in adult intensive care units in the United Kingdom. Anaesthesia. 2008 Sep;63(9):959-66. doi: 10.1111/j.1365-2044.2008.05514.x. Epub 2008 Jun 28.
citation: Borg R, Ugboma D, Walker DM, Partridge R. Evaluating the safety and efficacy of regional citrate compared to systemic heparin as anticoagulation for continuous renal replacement therapy in critically ill patients: A service evaluation following a change in practice. J Intensive Care Soc. 2017 Aug;18(3):184-192. doi: 10.1177/1751143717695835. Epub 2017 Mar 14.
citation: Cutts MW, Thomas AN, Kishen R. Transfusion requirements during continuous veno-venous haemofiltration: -the importance of filter life. Intensive Care Med. 2000 Nov;26(11):1694-7. doi: 10.1007/s001340000676.
citation: Morabito S, Pistolesi V, Tritapepe L, Fiaccadori E. Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephrol. 2014 Dec 5;9(12):2173-88. doi: 10.2215/CJN.01280214. Epub 2014 Jul 3.
citation: Tuerdi B, Zuo L, Sun H, Wang K, Wang Z, Li G. Safety and efficacy of regional citrate anticoagulation in continuous blood purification treatment of patients with multiple organ dysfunction syndrome. Braz J Med Biol Res. 2017 Nov 17;51(1):e6378. doi: 10.1590/1414-431X20176378.
citation: Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM. Biomarkers in acute kidney injury - pathophysiological basis and clinical performance. Acta Physiol (Oxf). 2017 Mar;219(3):554-572. doi: 10.1111/apha.12764. Epub 2016 Aug 25.
citation: Kwon O, Molitoris BA, Pescovitz M, Kelly KJ. Urinary actin, interleukin-6, and interleukin-8 may predict sustained ARF after ischemic injury in renal allografts. Am J Kidney Dis. 2003 May;41(5):1074-87. doi: 10.1016/s0272-6386(03)00206-3.
citation: Liangos O, Kolyada A, Tighiouart H, Perianayagam MC, Wald R, Jaber BL. Interleukin-8 and acute kidney injury following cardiopulmonary bypass: a prospective cohort study. Nephron Clin Pract. 2009;113(3):c148-54. doi: 10.1159/000232595. Epub 2009 Aug 12.
citation: de Fontnouvelle CA, Greenberg JH, Thiessen-Philbrook HR, Zappitelli M, Roth J, Kerr KF, Devarajan P, Shlipak M, Coca S, Parikh CR; TRIBE-AKI Consortium. Interleukin-8 and Tumor Necrosis Factor Predict Acute Kidney Injury After Pediatric Cardiac Surgery. Ann Thorac Surg. 2017 Dec;104(6):2072-2079. doi: 10.1016/j.athoracsur.2017.04.038. Epub 2017 Aug 16.
citation: Trakarnvanich T, Sirivongrangson P, Trongtrakul K, Srisawat N. The effect of citrate in cardiovascular system and clot circuit in critically ill patients requiring continuous renal replacement therapy. J Artif Organs. 2023 Mar;26(1):53-64. doi: 10.1007/s10047-022-01329-0. Epub 2022 Apr 12.