Investigating Different Anticoagulants for Renal Replacement Therapy

NCT02669589 | Completed Phase 4 DMC

• 3 other identifiers: UKM 14_00662014-004854-3303-AnIt-14
• Study Type: interventional
• Target: 638
• Locations: 1 country
• Sites: 31

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.

Conditions

Acute Kidney Injury

Keywords

CRRT; AKI; anticoagulation; KDIGO

Outcome Measures

Primary Outcomes (2)

• CRRT-filter life span in hours

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

  during continuous renal replacement therapy up to 1 year

• Overall survival in a 90day follow-up period

  90 days

Secondary Outcomes (11)

• ICU length of stay in days

  up to 1 year

• Hospital length of stay in days

  up to 1 year

• duration of renal replacement therapy

  1 year

• Bleeding complication

  intraoperative

• Number of patients with administration of red blood cells

  intraoperative

Other Outcomes (4)

• SOFA Scores (Sepsis-related Organ Failure Assessment score)

  day 1-14, 21 and 28 during ICU stay

• serum creatinine level in mg/dL

  Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation

• plasma urea concentration in mg/dl

  Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation

Study Arms (2)

heparin anticoagulation

ACTIVE COMPARATOR

Systemic anticoagulation of the continuous renal replacement therapy with heparin. Dose will be titrated to maintain aPTT (activated partial thromboplastin time) between 45-60s)

Drug: Heparin

citrate anticoagulation

EXPERIMENTAL

Regional anticoagulation of the continuous renal replacement therapy with citrate. Target posthemofilter ionized calcium level: 0.25-0.35 mmol/l

Drug: Citrate

Interventions

Heparin DRUG

heparin anticoagulation

Citrate DRUG

citrate anticoagulation

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Critically ill patients with clinical indication for CRRT (clinical decision to use continuous RRT due to hemodynamic instability)
• Severe acute kidney injury (KDIGO 3-classification) despite optimal resuscitation
• 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)
• years old
• Intention to provide full intensive care treatment for at least 3 days

You may not qualify if:

• 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)
• Disease or organ damage related with hemorrhagic diathesis (coagulopathy, thrombocytopenia, severe liver or pancreas disease)
• Dialysis-dependent chronic kidney insufficiency
• Need of therapeutic systemic anticoagulation
• Allergic reaction to one of the anticoagulants or ingredients, Heparin-induced thrombocytopenia
• AKI caused by permanent occlusion or surgical lesion of the renal artery
• AKI caused by (glomerulo)nephritis, interstitial nephritis, vasculitis or postrenal obstruction
• Do-not-resuscitate order
• Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura
• Persistent and severe lactate acidosis in the context of an acute liver failure and/or shock
• Kidney transplant within the last 12 months
• Pregnancy and nursing period
• Abortus imminens
• Participation in another clinical intervention trial in the last 3 months
• Persons with any kind of dependency on the investigator or employed by the sponsor or investigator

Sponsors & Collaborators

• University Hospital Muenster: lead
• University of Leipzig: collaborator
• German Research Foundation: collaborator

Study Sites (31)

University Hospital Aachen

Aachen, D-52074, Germany

Location

Klinikum Augsburg

Augsburg, D-86156, Germany

Location

HELIOS Klinikum Bad Saarow, Dept. of Intensive Care

Bad Saarow, D-15526, Germany

Location

Charité Berlin, Dept. of Anesthesiology and Intensive Care Medicine

Berlin, 10117, Germany

Location

Charité Berlin CCM, Medical Department, Division of Nephrology

Berlin, D-10117, Germany

Location

Charité Berlin CCV, Medical Department, Division of Nephrology

Berlin, D-13353, Germany

Location

Evangelisches Klinikum Bethel gGmbH

Bielefeld, D-33617, Germany

Location

Universitätsklinikum Knappschaftskrankenhaus Bochum

Bochum, D-44892, Germany

Location

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

Bonn, D-53127, Germany

Location

Klinikum Köln-Merheim, Medizinische Klinik I

Cologne, D-51109, Germany

Location

University Hospital Duesseldorf, Dept. of Anaesthesiology

Düsseldorf, D-40225, Germany

Location

University Hospital Düsseldorf, Dept. of Nephrology

Düsseldorf, D-40225, Germany

Location

University Hospital Erlangen

Erlangen, D-91054, Germany

Location

University Hospital Essen, Dept. for Nephrology

Essen, D-45122, Germany

Location

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

Frankfurt, D-60590, Germany

Location

University Hospital Gießen, Dept. of Anesthesiology and Intensive Care

Giessen, D-35392, Germany

Location

University Medical Center Göttingen, Dept. for Anesthesiology

Göttingen, D-37075, Germany

Location

University Medicine Greifswald

Greifswald, D-17475, Germany

Location

University Hospital Halle, Dept. of Anesthesiology and Intensive Care

Halle, D-06120, Germany

Location

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

Hamburg, D-20246, Germany

Location

University Hospital Heidelberg, Dept. of Anesthesiology

Heidelberg, D-69120, Germany

Location

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

Jena, D-07747, Germany

Location

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

Kiel, D-24105, Germany

Location

Universitätsklinikum Leipzig

Leipzig, D-04103, Germany

Location

Universitätsmedizin Mainz

Mainz, D-55131, Germany

Location

Technical University of Munich University Hospital, Dept. for Anaesthesiology

München, D-81675, Germany

Location

University Hospital Muenster

Münster, D-48149, Germany

Location

Klinikum Nürnberg

Nuremberg, D-90419, Germany

Location

University Hospital Regensburg, Dept. of Surgery

Regensburg, D-93042, Germany

Location

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

Solingen, D-42653, Germany

Location

University Hospital Tuebingen

Tübingen, D-72076, Germany

Location

Related Publications (4)

• von Groote T, Albert F, Meersch M, Koch R, Gerss J, Arlt B, Sadjadi M, Porschen C, Pickkers P, Zarbock A; RICH investigators. Evaluation of Proenkephalin A 119-159 for liberation from renal replacement therapy: an external, multicenter pilot study in critically ill patients with acute kidney injury. Crit Care. 2023 Jul 10;27(1):276. doi: 10.1186/s13054-023-04556-w.

  PMID: 37430375 DERIVED

• 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.

  PMID: 33314078 DERIVED

• 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.

  PMID: 33095849 DERIVED

• 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.

  PMID: 30670518 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Heparin; Citric Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Alexander Zarbock, MD

  University Hospital Muenster

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: February 1, 2016
• Study Start: March 1, 2016
• Primary Completion: April 3, 2019
• Study Completion: January 3, 2020
• Last Updated: February 19, 2020

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (31)