Citrate Versus Heparin in Continuous Renal Replacement Therapy :

NCT04865510 | Completed DMC

• 1 other identifier: COA033/61
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Kidney Injury; Citrate; Cytokines; Hemodynamic Responses

Outcome Measures

Primary Outcomes (4)

• Cardiac output

  cm3/min

  72 hour

• Cardiac index

  L/min/m2

  72 hour

• Systemic vascular resistance

  mmHg⋅min⋅mL-1

  72 hour

• Systemic vascular resistance index

  dynes · sec/cm5/m2

  72 hour

Secondary Outcomes (8)

• Filter life span

  through study completion,an aveage of 72 hours

• Changes of IL-1β

  day 1,day 3

• Changes of IL-6

  day 1,day 3

• Changes of IL-8

  day 1,day 3

• Changes of IL-10

  day 1,day 3

Study Arms (2)

Citrate

ACTIVE COMPARATOR

The RCA group CRRT were performed with Prisma flex or (Baxter Healthcare/Gambro Spain) or Informed machine with citrate pump. The function mode was continuous venovenous hemodiafiltration (CVVHDF) in postdilution mode with ST 150 filter sets. The substitution fluid was Accusol or Prismocal B22 .The dose of dialysis was 20-25 ml/kg/hr with blood flow 150-200 ml/min. Trisodium citrate solution (4%,136mmol/L) was infused into the arterial line prior to the blood pump at a dose of 4 mmol/L of plasma flow. Calcium chloride (5% 340 mmol/L elemental calcium) was infused into the venous return to maintain systemic ionized calcium in the normal range (0.99-1.30 mmol/L) and the targets values for ionized calcium (iCa2+) after the dialysis membrane were 0.25-0.35 mmol/L. The rale of calcium infusion was adjusted in a timely manner based on repeated measurements of calcium concentration

Procedure: Regional citrate anticoagulation

Heparin-free

PLACEBO COMPARATOR

The heparin- free group The circuit was periodically flushed with 50 ml saline via access limb every 30 minutes .When pre-filter pressure started to rise, additional saline flushes would be given.

Procedure: Regional citrate anticoagulation

Interventions

Regional citrate anticoagulation PROCEDURE

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 TNFα) . . 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).

Also known as: Heparin-free

Citrate; Heparin-free

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• need for CRRT,
• no contraindication to CRRT

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bangkok Metropolitan Administration Medical College and Vajira Hospital: lead
• King Chulalongkorn Memorial Hospital: collaborator
• Chiang Mai University: collaborator
• Department of Medicine, Somdech Phra Pinklao Hospital, Bangkok, Thailand.: collaborator

Study Sites (1)

Faculty of Medicine ,Vajira hospital,Navamindradhiraj University

Bangkok, 10300, Thailand

Location

Related Publications (11)

• 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.

  PMID: 21345279 RESULT

• 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.

  PMID: 18549413 RESULT

• 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.

  PMID: 29118829 RESULT

• 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.

  PMID: 11193279 RESULT

• 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.

  PMID: 24993448 RESULT

• 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.

  PMID: 29185591 RESULT

• 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.

  PMID: 27474473 RESULT

• 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.

  PMID: 12722043 RESULT

• 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.

  PMID: 19672112 RESULT

• 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.

  PMID: 28821332 RESULT

• 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.

  PMID: 35412099 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Thananda Trakarnvanich, M.D.

  Renal unit,Faculty of Medicine,Vajira Hospital,Navamindradhiraj University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: systemic random sampling (block of four). Group A was the citrate group while group B was heparin- free method.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This study is a prospective,multicenter, open-label randomized trial

Study Record Dates

• First Submitted: April 22, 2021
• First Posted: April 29, 2021
• Study Start: February 4, 2019
• Primary Completion: January 15, 2021
• Study Completion: March 31, 2021
• Last Updated: April 29, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)