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Investigating Different Anticoagulants for Renal Replacement Therapy (RICH)

Primary Purpose

Acute Kidney Injury

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Heparin
Citrate
Sponsored by
University Hospital Muenster
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Kidney Injury focused on measuring CRRT, AKI, anticoagulation, KDIGO

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital Aachen
  • Klinikum Augsburg
  • HELIOS Klinikum Bad Saarow, Dept. of Intensive Care
  • Charité Berlin, Dept. of Anesthesiology and Intensive Care Medicine
  • Charité Berlin CCM, Medical Department, Division of Nephrology
  • Charité Berlin CCV, Medical Department, Division of Nephrology
  • Evangelisches Klinikum Bethel gGmbH
  • Universitätsklinikum Knappschaftskrankenhaus Bochum
  • University Hospital Bonn, Dept.of Anesthesiology and Intensive Care Medicine
  • University Hospital Duesseldorf, Dept. of Anaesthesiology
  • University Hospital Düsseldorf, Dept. of Nephrology
  • University Hospital Erlangen
  • University Hospital Essen, Dept. for Nephrology
  • University Hospital Frankfurt, Dept. of Anesthesiology, Intensive-Care Medicine and Pain Therapy
  • University Hospital Gießen, Dept. of Anesthesiology and Intensive Care
  • University Medicine Greifswald
  • University Medical Center Göttingen, Dept. for Anesthesiology
  • University Hospital Halle, Dept. of Anesthesiology and Intensive Care
  • University Medical Center Hamburg-Eppendorf, Dept. of Intensive Care
  • University Hospital Heidelberg, Dept. of Anesthesiology
  • University Hospital Jena, Dept. of Anesthesiology and Intensive Care Medicine
  • University Hospital Schleswig-Holstein, Campus Kiel, Dept. for Anaesthesiology and Intensive Care
  • Klinikum Köln-Merheim, Medizinische Klinik I
  • Universitätsklinikum Leipzig
  • Universitätsmedizin Mainz
  • University Hospital Muenster
  • Technical University of Munich University Hospital, Dept. for Anaesthesiology
  • Klinikum Nürnberg
  • University Hospital Regensburg, Dept. of Surgery
  • Municipal Hospital Solingen, Dept. for Nephrology and General Internal Medicine
  • University Hospital Tuebingen

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

heparin anticoagulation

citrate anticoagulation

Arm Description

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

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

Outcomes

Primary Outcome Measures

CRRT-filter life span in hours
It will be reported how long the filter will be used during CRRT
Overall survival in a 90day follow-up period

Secondary Outcome Measures

ICU length of stay in days
The primary ICU stay will be documented.
Hospital length of stay in days
duration of renal replacement therapy
within 1 year after randomization
Bleeding complication
Number of patients with administration of red blood cells
Rate of infection
Major adverse kidney events
Complications of therapy
Recovery of renal function
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)
Number of participants with hemodialysis
Mortality

Full Information

First Posted
January 19, 2016
Last Updated
February 18, 2020
Sponsor
University Hospital Muenster
Collaborators
University of Leipzig, German Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02669589
Brief Title
Investigating Different Anticoagulants for Renal Replacement Therapy
Acronym
RICH
Official Title
Regional Citrate Versus Systemic Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
April 3, 2019 (Actual)
Study Completion Date
January 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Muenster
Collaborators
University of Leipzig, German Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury
Keywords
CRRT, AKI, anticoagulation, KDIGO

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
638 (Actual)

8. Arms, Groups, and Interventions

Arm Title
heparin anticoagulation
Arm Type
Active Comparator
Arm Description
Systemic anticoagulation of the continuous renal replacement therapy with heparin. Dose will be titrated to maintain aPTT (activated partial thromboplastin time) between 45-60s)
Arm Title
citrate anticoagulation
Arm Type
Experimental
Arm Description
Regional anticoagulation of the continuous renal replacement therapy with citrate. Target posthemofilter ionized calcium level: 0.25-0.35 mmol/l
Intervention Type
Drug
Intervention Name(s)
Heparin
Intervention Type
Drug
Intervention Name(s)
Citrate
Primary Outcome Measure Information:
Title
CRRT-filter life span in hours
Description
It will be reported how long the filter will be used during CRRT
Time Frame
during continuous renal replacement therapy up to 1 year
Title
Overall survival in a 90day follow-up period
Time Frame
90 days
Secondary Outcome Measure Information:
Title
ICU length of stay in days
Description
The primary ICU stay will be documented.
Time Frame
up to 1 year
Title
Hospital length of stay in days
Time Frame
up to 1 year
Title
duration of renal replacement therapy
Description
within 1 year after randomization
Time Frame
1 year
Title
Bleeding complication
Time Frame
intraoperative
Title
Number of patients with administration of red blood cells
Time Frame
intraoperative
Title
Rate of infection
Time Frame
during primary ICU stay up to 1 year
Title
Major adverse kidney events
Time Frame
day 28, 60, 90 and after 1 year after start of CRRT
Title
Complications of therapy
Time Frame
intraoperative
Title
Recovery of renal function
Description
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)
Time Frame
day 28, 60, 90 and 1 year after start of CRRT
Title
Number of participants with hemodialysis
Time Frame
day 28, 60, 90 and 1 year after start of CRRT
Title
Mortality
Time Frame
day 28, 60 and 1-year
Other Pre-specified Outcome Measures:
Title
SOFA Scores (Sepsis-related Organ Failure Assessment score)
Time Frame
day 1-14, 21 and 28 during ICU stay
Title
serum creatinine level in mg/dL
Time Frame
Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
Title
plasma urea concentration in mg/dl
Time Frame
Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
Title
glomerular filtration rate
Time Frame
Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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) 18-90 years old Intention to provide full intensive care treatment for at least 3 days Written informed consent of the patient or the legal representatives or the authorized representative or the inclusion due to an emergency situation Exclusion Criteria: 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 No hemofiltration machine free for use at the moment of inclusion 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 Persons held in an institution by legal or official order
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Zarbock, MD
Organizational Affiliation
University Hospital Muenster
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital Aachen
City
Aachen
ZIP/Postal Code
D-52074
Country
Germany
Facility Name
Klinikum Augsburg
City
Augsburg
ZIP/Postal Code
D-86156
Country
Germany
Facility Name
HELIOS Klinikum Bad Saarow, Dept. of Intensive Care
City
Bad Saarow
ZIP/Postal Code
D-15526
Country
Germany
Facility Name
Charité Berlin, Dept. of Anesthesiology and Intensive Care Medicine
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Charité Berlin CCM, Medical Department, Division of Nephrology
City
Berlin
ZIP/Postal Code
D-10117
Country
Germany
Facility Name
Charité Berlin CCV, Medical Department, Division of Nephrology
City
Berlin
ZIP/Postal Code
D-13353
Country
Germany
Facility Name
Evangelisches Klinikum Bethel gGmbH
City
Bielefeld
ZIP/Postal Code
D-33617
Country
Germany
Facility Name
Universitätsklinikum Knappschaftskrankenhaus Bochum
City
Bochum
ZIP/Postal Code
D-44892
Country
Germany
Facility Name
University Hospital Bonn, Dept.of Anesthesiology and Intensive Care Medicine
City
Bonn
ZIP/Postal Code
D-53127
Country
Germany
Facility Name
University Hospital Duesseldorf, Dept. of Anaesthesiology
City
Duesseldorf
ZIP/Postal Code
D-40225
Country
Germany
Facility Name
University Hospital Düsseldorf, Dept. of Nephrology
City
Düsseldorf
ZIP/Postal Code
D-40225
Country
Germany
Facility Name
University Hospital Erlangen
City
Erlangen
ZIP/Postal Code
D-91054
Country
Germany
Facility Name
University Hospital Essen, Dept. for Nephrology
City
Essen
ZIP/Postal Code
D-45122
Country
Germany
Facility Name
University Hospital Frankfurt, Dept. of Anesthesiology, Intensive-Care Medicine and Pain Therapy
City
Frankfurt
ZIP/Postal Code
D-60590
Country
Germany
Facility Name
University Hospital Gießen, Dept. of Anesthesiology and Intensive Care
City
Gießen
ZIP/Postal Code
D-35392
Country
Germany
Facility Name
University Medicine Greifswald
City
Greifswald
ZIP/Postal Code
D-17475
Country
Germany
Facility Name
University Medical Center Göttingen, Dept. for Anesthesiology
City
Göttingen
ZIP/Postal Code
D-37075
Country
Germany
Facility Name
University Hospital Halle, Dept. of Anesthesiology and Intensive Care
City
Halle (Saale)
ZIP/Postal Code
D-06120
Country
Germany
Facility Name
University Medical Center Hamburg-Eppendorf, Dept. of Intensive Care
City
Hamburg
ZIP/Postal Code
D-20246
Country
Germany
Facility Name
University Hospital Heidelberg, Dept. of Anesthesiology
City
Heidelberg
ZIP/Postal Code
D-69120
Country
Germany
Facility Name
University Hospital Jena, Dept. of Anesthesiology and Intensive Care Medicine
City
Jena
ZIP/Postal Code
D-07747
Country
Germany
Facility Name
University Hospital Schleswig-Holstein, Campus Kiel, Dept. for Anaesthesiology and Intensive Care
City
Kiel
ZIP/Postal Code
D-24105
Country
Germany
Facility Name
Klinikum Köln-Merheim, Medizinische Klinik I
City
Köln
ZIP/Postal Code
D-51109
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
D-04103
Country
Germany
Facility Name
Universitätsmedizin Mainz
City
Mainz
ZIP/Postal Code
D-55131
Country
Germany
Facility Name
University Hospital Muenster
City
Muenster
ZIP/Postal Code
D-48149
Country
Germany
Facility Name
Technical University of Munich University Hospital, Dept. for Anaesthesiology
City
München
ZIP/Postal Code
D-81675
Country
Germany
Facility Name
Klinikum Nürnberg
City
Nürnberg
ZIP/Postal Code
D-90419
Country
Germany
Facility Name
University Hospital Regensburg, Dept. of Surgery
City
Regensburg
ZIP/Postal Code
D-93042
Country
Germany
Facility Name
Municipal Hospital Solingen, Dept. for Nephrology and General Internal Medicine
City
Solingen
ZIP/Postal Code
D-42653
Country
Germany
Facility Name
University Hospital Tuebingen
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33314078
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.
Results Reference
derived
PubMed Identifier
33095849
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.
Results Reference
derived
PubMed Identifier
30670518
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.
Results Reference
derived

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Investigating Different Anticoagulants for Renal Replacement Therapy

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