Citrate Versus Heparin in Continuous Renal Replacement Therapy :

Acute Kidney Injury Clinical Trial

Official title:

Citrate Versus Heparin in Continuous Renal Replacement Therapy : Effect on Cardiovascular System and Clot Circuit in Critically Ill Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04865510
• Other study ID #: COA033/61
• Status: Completed
• Phase: N/A
• Start date: February 4, 2019
• Est. completion date: March 31, 2021

Study information

• Verified date: April 2021
• Source: Bangkok Metropolitan Administration Medical College and Vajira Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: March 31, 2021
• Est. primary completion date: January 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Kidney Injury
• Citrate
• Cytokines

Intervention

Procedure:
• Regional citrate anticoagulation
The investigators collected patient's plasma at study start (day 0) and at day 3, 5, 7, 14, 28) .Samples were used to measure inflammatory markers (Il 6, IL 8, IL 10 and TNFa) . . Markers of dialysis efficiency (BUN, creatinine) and other parameters related to AKI (acid base status, calcium, phosphorus, hemoglobin). The recorded variables also included adverse events, dialysis clotting, hemodynamic status, duration of mechanical ventilation, inotropic support. The hemodynamic parameters were monitored by EV 1000 clinical platform .The investigators measured cardiac performance data, which includes cardiac output (CO), cardiac index (CI), stroke volume (SV), and stroke volume indexes (SVI). Moreover, it also provides information about systemic vascular resistance (SVR). Thus, patient hemodynamic parameters as mentioned above were measured at the following 6 time-point: after the initiation of CRRT (T1), every 6 hours later for 24 hours (T2, T3, T4, T5), and at hour-72 (T6).

Locations

Country	Name	City	State
Thailand	Faculty of Medicine ,Vajira hospital,Navamindradhiraj University	Bangkok

Sponsors (4)

Lead Sponsor	Collaborator
Bangkok Metropolitan Administration Medical College and Vajira Hospital	Chiang Mai University, Department of Medicine, Somdech Phra Pinklao Hospital, Bangkok, Thailand., King Chulalongkorn Memorial Hospital

Country where clinical trial is conducted

Thailand, 

References & Publications (10)

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 i — View 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. — View 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. A — View 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 — View 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. — View 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. — View 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. Review. — View 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. Review. — View 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. Review. — View 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: 10.15 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac output	cm3/min	72 hour
Primary	Cardiac index	L/min/m2	72 hour
Primary	Systemic vascular resistance	mmHg·min·mL-1	72 hour
Primary	Systemic vascular resistance index	dynes · sec/cm5/m2	72 hour
Secondary	Filter life span	Hours of filter use	through study completion,an aveage of 72 hours
Secondary	Changes of IL-1ß	Unit/ml	day 1,day 3
Secondary	Changes of IL-6	Unit/ml	day 1,day 3
Secondary	Changes of IL-8	Units/ml	day 1,day 3
Secondary	Changes of IL-10	Units/mL	day 1,day 3
Secondary	Changes of TNF-?	Uniys/mL	day 1,day 3
Secondary	Mortality	patient survival	28 day
Secondary	Renal survival	dialysis dependent	28 day