Investigating Different Anticoagulants for Renal Replacement Therapy

NCT ID: NCT02669589

Last Updated: 2020-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 638 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2020-01-03

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

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

heparin anticoagulation

Systemic anticoagulation of the continuous renal replacement therapy with heparin.

Dose will be titrated to maintain aPTT (activated partial thromboplastin time) between 45-60s)

Group Type: ACTIVE_COMPARATOR

Heparin

Intervention Type: DRUG

citrate anticoagulation

Regional anticoagulation of the continuous renal replacement therapy with citrate.

Target posthemofilter ionized calcium level: 0.25-0.35 mmol/l

Group Type: EXPERIMENTAL

Citrate

Intervention Type: DRUG

Interventions

Heparin

Intervention Type: DRUG

Citrate

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Leipzig

OTHER

Sponsor Role: collaborator

German Research Foundation

OTHER

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexander Zarbock, MD

Role: STUDY_CHAIR

University Hospital Muenster

Locations

University Hospital Aachen

Aachen, , Germany

Klinikum Augsburg

Augsburg, , Germany

HELIOS Klinikum Bad Saarow, Dept. of Intensive Care

Bad Saarow, , Germany

Charité Berlin, Dept. of Anesthesiology and Intensive Care Medicine

Berlin, , Germany

Charité Berlin CCM, Medical Department, Division of Nephrology

Berlin, , Germany

Charité Berlin CCV, Medical Department, Division of Nephrology

Berlin, , Germany

Evangelisches Klinikum Bethel gGmbH

Bielefeld, , Germany

Universitätsklinikum Knappschaftskrankenhaus Bochum

Bochum, , Germany

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

Bonn, , Germany

Klinikum Köln-Merheim, Medizinische Klinik I

Cologne, , Germany

University Hospital Duesseldorf, Dept. of Anaesthesiology

Düsseldorf, , Germany

University Hospital Düsseldorf, Dept. of Nephrology

Düsseldorf, , Germany

University Hospital Erlangen

Erlangen, , Germany

University Hospital Essen, Dept. for Nephrology

Essen, , Germany

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

Frankfurt, , Germany

University Hospital Gießen, Dept. of Anesthesiology and Intensive Care

Giessen, , Germany

University Medical Center Göttingen, Dept. for Anesthesiology

Göttingen, , Germany

University Medicine Greifswald

Greifswald, , Germany

University Hospital Halle, Dept. of Anesthesiology and Intensive Care

Halle, , Germany

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

Hamburg, , Germany

University Hospital Heidelberg, Dept. of Anesthesiology

Heidelberg, , Germany

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

Jena, , Germany

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

Kiel, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Universitätsmedizin Mainz

Mainz, , Germany

Technical University of Munich University Hospital, Dept. for Anaesthesiology

München, , Germany

University Hospital Muenster

Münster, , Germany

Klinikum Nürnberg

Nuremberg, , Germany

University Hospital Regensburg, Dept. of Surgery

Regensburg, , Germany

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

Solingen, , Germany

University Hospital Tuebingen

Tübingen, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 37430375 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33314078 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33095849 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30670518 (View on PubMed)

Other Identifiers

2014-004854-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

03-AnIt-14

Identifier Type: OTHER

Identifier Source: secondary_id

UKM 14_0066

Identifier Type: -

Identifier Source: org_study_id