Clinical trial NCT02669589: Investigating Different Anticoagulants for Renal Replacement Therapy
Official title: Regional Citrate Versus Systemic Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Kidney Injury
Keywords: CRRT
AKI
anticoagulation
KDIGO
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: University of Leipzig
name: German Research Foundation
First posted: 2016-02-01
Enrollment: 638
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the effect of regional citrate anticoagulation within the scope of continuous renal replacement (CRRT) in critically ill patients with acute kidney injury (AKI) on filter life span and 90-day all cause mortality.

Detailed description: Purpose of clinical trial:

To evaluate the effect of regional citrate anticoagulation within the scope of continuous renal replacement (CRRT) in critically ill patients with acute kidney injury (AKI) on filter life span and 90-day all cause mortality.

Patient population: critically ill patients with acute kidney injury requiring renal replacement therapy.

Primary objective:

Anticoagulation of the extracorporeal circuit is required in continuous RRT (CRRT). To this date, it is not clear which anticoagulant should be used for CRRT. Regional citrate anticoagulation (RCA) for CRRT in critically ill patients with AKI prolongs filter life span and reduces 90-day all cause mortality by approximately 8% (from 48% to 40%) compared to systemic heparin anticoagulation for CRRT

Eligibility criteria: Inclusion Criteria:

1. Critically ill patients with clinical indication for CRRT (clinical decision to use continuous RRT due to hemodynamic instability)

   Or

   Severe acute kidney injury (KDIGO 3-classification) despite optimal resuscitation
2. At least one of the following conditions

   * Sepsis or septic shock
   * Use of catecholamines (norepinephrine or epinephrine ≥ 0.1 µg/kg/min or norepinephrine ≥ 0.05 µg/kg/min + dobutamine (any dose) or norepinephrine ≥ 0.05 µg/kg/min + vasopressin (any dose) or epinephrine ≥ 0.05 µg/kg/min + norepinephrine ≥ 0.05 µg/kg/min)
   * Refractory fluid overload: worsening pulmonary edema: PaO2/FiO2 \< 300 mmHg and/or fluid balance \> 10% of body weight)
3. 18-90 years old
4. Intention to provide full intensive care treatment for at least 3 days
5. Written informed consent of the patient or the legal representatives or the authorized representative or the inclusion due to an emergency situation

Exclusion Criteria:

1. Patients with increased bleeding risk (e.g. an active bleeding from ulcers in the gastro-intestinal tract, hypertension with a diastolic blood pressure higher than 105 mm Hg, injuries (intracranial hemorrhage, aneurysm of brain arteries) of or surgical procedures on the central nervous system if a heparinization with a target aPTT 45-60 s is not allowed by the treating neurologist or neurosurgeon, severe retinopathies, bleeding into the vitreum, ophthalmic surgical procedures)) or injuries, active tuberculosis; infective endocarditis)
2. Disease or organ damage related with hemorrhagic diathesis (coagulopathy, thrombocytopenia, severe liver or pancreas disease)
3. Dialysis-dependent chronic kidney insufficiency
4. Need of therapeutic systemic anticoagulation
5. Allergic reaction to one of the anticoagulants or ingredients, Heparin-induced thrombocytopenia
6. AKI caused by permanent occlusion or surgical lesion of the renal artery
7. AKI caused by (glomerulo)nephritis, interstitial nephritis, vasculitis or postrenal obstruction
8. Do-not-resuscitate order
9. Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura
10. Persistent and severe lactate acidosis in the context of an acute liver failure and/or shock
11. Kidney transplant within the last 12 months
12. Pregnancy and nursing period
13. Abortus imminens
14. No hemofiltration machine free for use at the moment of inclusion
15. Participation in another clinical intervention trial in the last 3 months
16. Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
17. Persons held in an institution by legal or official order

Primary outcomes:
measure: CRRT-filter life span in hours
timeFrame: during continuous renal replacement therapy up to 1 year
measure: Overall survival in a 90day follow-up period
timeFrame: 90 days
Secondary outcomes:
measure: ICU length of stay in days
timeFrame: up to 1 year
measure: Hospital length of stay in days
timeFrame: up to 1 year
measure: duration of renal replacement therapy
timeFrame: 1 year
measure: Bleeding complication
timeFrame: intraoperative
measure: Number of patients with administration of red blood cells
timeFrame: intraoperative
measure: Rate of infection
timeFrame: during primary ICU stay up to 1 year
measure: Major adverse kidney events
timeFrame: day 28, 60, 90 and after 1 year after start of CRRT
measure: Complications of therapy
timeFrame: intraoperative
measure: Recovery of renal function
timeFrame: day 28, 60, 90 and 1 year after start of CRRT
measure: Number of participants with hemodialysis
timeFrame: day 28, 60, 90 and 1 year after start of CRRT
measure: Mortality
timeFrame: day 28, 60 and 1-year
Other outcomes:
measure: SOFA Scores (Sepsis-related Organ Failure Assessment score)
timeFrame: day 1-14, 21 and 28 during ICU stay
measure: serum creatinine level in mg/dL
timeFrame: Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
measure: plasma urea concentration in mg/dl
timeFrame: Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
measure: glomerular filtration rate
timeFrame: Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
Locations:
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Augsburg
country: Germany
facility: Klinikum Augsburg
city: Bad Saarow
country: Germany
facility: HELIOS Klinikum Bad Saarow, Dept. of Intensive Care
city: Berlin
country: Germany
facility: Charité Berlin, Dept. of Anesthesiology and Intensive Care Medicine
city: Berlin
country: Germany
facility: Charité Berlin CCM, Medical Department, Division of Nephrology
city: Berlin
country: Germany
facility: Charité Berlin CCV, Medical Department, Division of Nephrology
city: Bielefeld
country: Germany
facility: Evangelisches Klinikum Bethel gGmbH
city: Bochum
country: Germany
facility: Universitätsklinikum Knappschaftskrankenhaus Bochum
city: Bonn
country: Germany
facility: University Hospital Bonn, Dept.of Anesthesiology and Intensive Care Medicine
city: Duesseldorf
country: Germany
facility: University Hospital Duesseldorf, Dept. of Anaesthesiology
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf, Dept. of Nephrology
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Essen
country: Germany
facility: University Hospital Essen, Dept. for Nephrology
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt, Dept. of Anesthesiology, Intensive-Care Medicine and Pain Therapy
city: Gießen
country: Germany
facility: University Hospital Gießen, Dept. of Anesthesiology and Intensive Care
city: Greifswald
country: Germany
facility: University Medicine Greifswald
city: Göttingen
country: Germany
facility: University Medical Center Göttingen, Dept. for Anesthesiology
city: Halle (Saale)
country: Germany
facility: University Hospital Halle, Dept. of Anesthesiology and Intensive Care
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf, Dept. of Intensive Care
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Dept. of Anesthesiology
city: Jena
country: Germany
facility: University Hospital Jena, Dept. of Anesthesiology and Intensive Care Medicine
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein, Campus Kiel, Dept. for Anaesthesiology and Intensive Care
city: Köln
country: Germany
facility: Klinikum Köln-Merheim, Medizinische Klinik I
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Muenster
country: Germany
facility: University Hospital Muenster
city: München
country: Germany
facility: Technical University of Munich University Hospital, Dept. for Anaesthesiology
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Regensburg
country: Germany
facility: University Hospital Regensburg, Dept. of Surgery
city: Solingen
country: Germany
facility: Municipal Hospital Solingen, Dept. for Nephrology and General Internal Medicine
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
Study officials:
affiliation: University Hospital Muenster
name: Alexander Zarbock, MD
role: STUDY_CHAIR
References:
citation: Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3.
citation: Zarbock A, Kullmar M, Kindgen-Milles D, Wempe C, Gerss J, Brandenburger T, Dimski T, Tyczynski B, Jahn M, Mulling N, Mehrlander M, Rosenberger P, Marx G, Simon TP, Jaschinski U, Deetjen P, Putensen C, Schewe JC, Kluge S, Jarczak D, Slowinski T, Bodenstein M, Meybohm P, Wirtz S, Moerer O, Kortgen A, Simon P, Bagshaw SM, Kellum JA, Meersch M; RICH Investigators and the Sepnet Trial Group. 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. JAMA. 2020 Oct 27;324(16):1629-1639. doi: 10.1001/jama.2020.18618.
citation: Meersch M, Kullmar M, Wempe C, Kindgen-Milles D, Kluge S, Slowinski T, Marx G, Gerss J, Zarbock A; SepNet Critical Care Trials Group. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH) trial: study protocol for a multicentre, randomised controlled trial. BMJ Open. 2019 Jan 21;9(1):e024411. doi: 10.1136/bmjopen-2018-024411.