Comparison of Slow Efficiency Daily Dialysis (SLEDD) With Unfractionated Heparin Versus Citrasate in Critically Ill Patients.

The purpose of this study is to compare the feasibility, safety and efficacy of hemodialysis with unfractionated heparin compared to hemodialysis with Citrasate in Critically Ill Patients.

Study Overview

• Status: Unknown
• Conditions: Hemodialysis; Acute Kidney Injury
• Intervention / Treatment: Drug: Unfractionated heparin; Drug: Citrasate

Detailed Description

Objective : To compare the feasibility, safety and efficacy of Sustained Low Efficiency Daily Hemodialysis (SLEDD) using regional anticoagulation with Citrasate® compared to systemic anticoagulation with unfractionated heparin in critically ill patients.

Design : Prospective, randomized, single-center clinical trial Setting : mixed medical-surgical 45 bed ICU in a tertiary university hospital Patients : 250 patients with Acute Kidney Injury (AKI) stage III needing renal replacement therapy Interventions : Patients are randomized to receive SLEDD using standard dialysate and systemic anticoagulation with UF versus SLEDD using Citrasate®-dialysate with no additional UF.

Measurements and main results :

Primary end point :

- The incidence of premature interruptions of the dialysis procedure attributed to hemofilter clotting.

Secondary end points :

• The incidence of bleeding episodes as defined by the WHO-criteria
• The transfusion requirements
• The incidence of technique failure
• The incidence of metabolic derangements (metabolic alkalosis, metabolic acidosis, hypocalcemia, hypercalcemia, hypernatremia, hyponatremia)
• The incidence of citrate intoxication
• The dialysis efficiency expressed as Kt/V and URR

Tertiary end points :

- All cause mortality at day 28 and day 90 after inclusion

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Walter Verbrugghe, MD; Phone Number: 003238214149; Email: walter.Verbrugghe@uza.be
• Study Contact Backup: Name: Philippe Jorens, PhD, MD; Phone Number: 003238213639; Email: philippe.jorens@uza.be

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Critical Care Department of the Antwerp University Hospital, Belgium
    • Contact: Walter Verbrugghe, MD; Phone Number: 003238214149; Email: walter.Verbrugghe@uza.be
    • Contact: Philippe Jorens, PhD, MD; Phone Number: 003238213639; Email: philippe.jorens@uza.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Need for hemodialysis in the ICU for at least one treatment
• No prior hemodialysis treatment in the ICU except continuous renal replacement therapy

Exclusion Criteria:

• Need for systemic anticoagulation with unfractionated or fractionated heparin, oral anticoagulants or intravenous anti-aggregants for other reasons
• Need for continued thrombolysis therapy within the 6 hours before inclusion
• Need for continued treatment with activated protein C (drotrecogin alfa) within the 12 hours before inclusion
• Need for continued treatment with intravenous anti-aggregants (abciximab, eptifabide) within 12 hours before inclusion
• Liver failure (acute and acute-on-chronic)
• Confirmed or suspected Heparin Induced Thrombocytopenia (HIT)
• Heparin allergies
• Severe uncorrected hypocalcemia (ionized calcium < 0,8 mmol/l)
• Refusal of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Anticoagulation; Hemodialysis is performed using standard anticoagulation using unfractionated heparin if no contra-indications for the use of heparin exist. If contra-indications for heparin exist a heparin coated hemofilter (Evodial) will be used. The use of unfractionated heparin or no heparin (with coated hemofilter) is a decision to be taken before every hemodialysis.	Drug: Unfractionated heparin; dose 5-10 IU/kg/hrs adaptations of infusion rate upon APTT measurements during hemodialysis; Other Names: Unfractionated Heparin, LEO laboratories Ltd, MA #PL 0043/0041R
Experimental: Citrasate; Hemodialysis is performed with Citrasate	Drug: Citrasate; Citrasate is infused as a dialysate; Other Names: Citrasate, Advanced Renal Technologies, MA #K000792

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of premature interruptions of the dialysis procedure attributed to hemofilter clotting.	6 hours after starting dialysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of technique failure defined as the number of patients who develop a contra-indication for the allocated anticoagulation regimen during the study period		during whole wtudy
The incidence of bleeding episodes. A bleeding episode is defined according to the WHO bleeding criteria		during the whole study period
The transfusion requirements defined as the total of units blood products administrated during the ICU stay and per dialysis treatment		during the whole study period
The incidence of metabolic derangements during the study period	Metabolic alkalosis (defined as a pH > 7,5 and a bicarbonate > 24 mmol/l); Metabolic acidosis (defined as a pH < 7,25 and a bicarbonate < 18 mmol/l); Hypocalcemia (defined as an ionized calcium < 0,9 mmol/l); Hypercalcemia (defined as an ionized calcium > 1,2 mol/l); Hypernatremia (defined as a Na+ > 145 mmol/l); Hyponatremia (defined a a Na+ < 130 mmol/l); Citrate toxicity (defined as a total calcium/ionized calcium ratio > 2,5)	during the whole study period
Dialysis efficiency expressed as Kt/V and URR		6 hours after starting dialysis

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Karin Jansen-Van doorn, MD, Staff member Nephrology Department; Principal Investigator: Gert Verpooten, PhD, MD, Head of Nephrology Department, University Hospital Antwerp, Belgium; Principal Investigator: Walter Verbrugghe, MD, Staff member Critical Care Department, Antwerp University Hospital, Belgium; Principal Investigator: Philippe Jorens, PhD, MD, Head of Critical Care Department, Antwerp University Hospital, Belgium

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): January 1, 2012
• Study Completion (Anticipated): January 1, 2013

Study Registration Dates

• First Submitted: October 25, 2010
• First Submitted That Met QC Criteria: October 25, 2010
• First Posted (Estimate): October 26, 2010

Study Record Updates

• Last Update Posted (Estimate): October 26, 2010
• Last Update Submitted That Met QC Criteria: October 25, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Anticoagulation; Hemodialysis; Intensive Care Medicine; Critical Ill Patients
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: 10/27/179; 2010-021665-68 (EudraCT Number)