MedPath

Investigating Different Anticoagulants for Renal Replacement Therapy

Phase 4
Completed
Conditions
Acute Kidney Injury
Interventions
Drug: Citrate
Registration Number
NCT02669589
Lead Sponsor
University Hospital Muenster
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
638
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
citrate anticoagulationCitrateRegional anticoagulation of the continuous renal replacement therapy with citrate. Target posthemofilter ionized calcium level: 0.25-0.35 mmol/l
heparin anticoagulationHeparinSystemic anticoagulation of the continuous renal replacement therapy with heparin. Dose will be titrated to maintain aPTT (activated partial thromboplastin time) between 45-60s)
Primary Outcome Measures
NameTimeMethod
CRRT-filter life span in hoursduring continuous renal replacement therapy up to 1 year

It will be reported how long the filter will be used during CRRT

Overall survival in a 90day follow-up period90 days
Secondary Outcome Measures
NameTimeMethod
Hospital length of stay in daysup to 1 year
Number of patients with administration of red blood cellsintraoperative
Major adverse kidney eventsday 28, 60, 90 and after 1 year after start of CRRT
ICU length of stay in daysup to 1 year

The primary ICU stay will be documented.

duration of renal replacement therapy1 year

within 1 year after randomization

Bleeding complicationintraoperative
Rate of infectionduring primary ICU stay up to 1 year
Complications of therapyintraoperative
Number of participants with hemodialysisday 28, 60, 90 and 1 year after start of CRRT
Recovery of renal functionday 28, 60, 90 and 1 year after start of CRRT

The recovery of renal function will be defined as composite endpoint consisting of lack of dialysis dependency and serum creatinine level no more than 0.5 mg/dl above the baseline value)

Mortalityday 28, 60 and 1-year

Trial Locations

Locations (31)

University Hospital Aachen

🇩🇪

Aachen, Germany

Klinikum Augsburg

🇩🇪

Augsburg, Germany

HELIOS Klinikum Bad Saarow, Dept. of Intensive Care

🇩🇪

Bad Saarow, Germany

Charité Berlin CCV, Medical Department, Division of Nephrology

🇩🇪

Berlin, Germany

Evangelisches Klinikum Bethel gGmbH

🇩🇪

Bielefeld, Germany

University Hospital Bonn, Dept.of Anesthesiology and Intensive Care Medicine

🇩🇪

Bonn, Germany

Universitätsklinikum Knappschaftskrankenhaus Bochum

🇩🇪

Bochum, Germany

University Hospital Frankfurt, Dept. of Anesthesiology, Intensive-Care Medicine and Pain Therapy

🇩🇪

Frankfurt, Germany

University Hospital Essen, Dept. for Nephrology

🇩🇪

Essen, Germany

University Hospital Duesseldorf, Dept. of Anaesthesiology

🇩🇪

Duesseldorf, Germany

University Hospital Düsseldorf, Dept. of Nephrology

🇩🇪

Düsseldorf, Germany

University Hospital Erlangen

🇩🇪

Erlangen, Germany

University Medicine Greifswald

🇩🇪

Greifswald, Germany

University Medical Center Göttingen, Dept. for Anesthesiology

🇩🇪

Göttingen, Germany

University Medical Center Hamburg-Eppendorf, Dept. of Intensive Care

🇩🇪

Hamburg, Germany

University Hospital Halle, Dept. of Anesthesiology and Intensive Care

🇩🇪

Halle (Saale), Germany

University Hospital Heidelberg, Dept. of Anesthesiology

🇩🇪

Heidelberg, Germany

University Hospital Schleswig-Holstein, Campus Kiel, Dept. for Anaesthesiology and Intensive Care

🇩🇪

Kiel, Germany

University Hospital Jena, Dept. of Anesthesiology and Intensive Care Medicine

🇩🇪

Jena, Germany

Klinikum Köln-Merheim, Medizinische Klinik I

🇩🇪

Köln, Germany

Klinikum Nürnberg

🇩🇪

Nürnberg, Germany

Technical University of Munich University Hospital, Dept. for Anaesthesiology

🇩🇪

München, Germany

University Hospital Muenster

🇩🇪

Muenster, Germany

University Hospital Regensburg, Dept. of Surgery

🇩🇪

Regensburg, Germany

Municipal Hospital Solingen, Dept. for Nephrology and General Internal Medicine

🇩🇪

Solingen, Germany

University Hospital Tuebingen

🇩🇪

Tuebingen, Germany

University Hospital Gießen, Dept. of Anesthesiology and Intensive Care

🇩🇪

Gießen, Germany

Universitätsklinikum Leipzig

🇩🇪

Leipzig, Germany

Universitätsmedizin Mainz

🇩🇪

Mainz, Germany

Charité Berlin, Dept. of Anesthesiology and Intensive Care Medicine

🇩🇪

Berlin, Germany

Charité Berlin CCM, Medical Department, Division of Nephrology

🇩🇪

Berlin, Germany

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