Investigating Different Anticoagulants for Renal Replacement Therapy

Acute Kidney Injury Clinical Trial

— RICH  

Official title:

Regional Citrate Versus Systemic Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02669589
• Other study ID #: UKM 14_0066
• Secondary ID: 2014-004854-3303
• Status: Completed
• Phase: Phase 4
• Start date: March 2016
• Est. completion date: January 3, 2020

Study information

• Verified date: February 2019
• Source: University Hospital Muenster
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 638
• Est. completion date: January 3, 2020
• Est. primary completion date: April 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury

Intervention

Drug:
• Heparin

• Citrate

Locations

Country	Name	City	State
Germany	University Hospital Aachen	Aachen
Germany	Klinikum Augsburg	Augsburg
Germany	HELIOS Klinikum Bad Saarow, Dept. of Intensive Care	Bad Saarow
Germany	Charité Berlin CCM, Medical Department, Division of Nephrology	Berlin
Germany	Charité Berlin CCV, Medical Department, Division of Nephrology	Berlin
Germany	Charité Berlin, Dept. of Anesthesiology and Intensive Care Medicine	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	University Hospital Duesseldorf, Dept. of Anaesthesiology	Duesseldorf
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 (Saale)
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	Klinikum Köln-Merheim, Medizinische Klinik I	Köln
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsmedizin Mainz	Mainz
Germany	University Hospital Muenster	Muenster
Germany	Technical University of Munich University Hospital, Dept. for Anaesthesiology	München
Germany	Klinikum Nürnberg	Nürnberg
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

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Muenster	German Research Foundation, University of Leipzig

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SOFA Scores (Sepsis-related Organ Failure Assessment score)		day 1-14, 21 and 28 during ICU stay
Other	serum creatinine level in mg/dL		Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
Other	plasma urea concentration in mg/dl		Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
Other	glomerular filtration rate		Day 0, day 1, day 3, day 5 and 1 day after CRRT cessation
Primary	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
Primary	Overall survival in a 90day follow-up period		90 days
Secondary	ICU length of stay in days	The primary ICU stay will be documented.	up to 1 year
Secondary	Hospital length of stay in days		up to 1 year
Secondary	duration of renal replacement therapy	within 1 year after randomization	1 year
Secondary	Bleeding complication		intraoperative
Secondary	Number of patients with administration of red blood cells		intraoperative
Secondary	Rate of infection		during primary ICU stay up to 1 year
Secondary	Major adverse kidney events		day 28, 60, 90 and after 1 year after start of CRRT
Secondary	Complications of therapy		intraoperative
Secondary	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)	day 28, 60, 90 and 1 year after start of CRRT
Secondary	Number of participants with hemodialysis		day 28, 60, 90 and 1 year after start of CRRT
Secondary	Mortality		day 28, 60 and 1-year