Efficacy, Safety and Pharmacokinetics of Tinzaparin During Slow Low Efficient Daily Dialysis in Intensive Care Patients (Tinza-SLEDD)

This study evaluates the pharmacokinetics of tinzaparin during renal replacement therapy (RRT).

60 patients with clinical indication for pharmacological thromboprophylaxis and slow low efficient daily dialysis (SLEDD) will be studied in Tampere University Hospital. All subjects will receive a 4500 IU bolus of tinzaparin. The subjects in study group (n=30) will also receive a 4500 IU continuous infusion of tinzaparin.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Renal Replacement Therapy; Anticoagulants
• Intervention / Treatment: Drug: Tinzaparin bolus; Drug: Tinzaparin continuous infusion

Detailed Description

After written informed consent, 60 subjects with clinical indication for pharmacological thromboprophylaxis and SLEDD will be studied in the Tampere University Hospital intensive care unit. After inclusion the subjects will be randomly assigned into study group (30 patients) and control (30 patients).

All subjects receive a bolus of tinzaparin 4500 IU into the inlet line of dialyzer at 5 minutes after the start of blood pump. Afterwards the subjects in the study group will continue to receive continuous tinzaparin infusion (concentration 100 IU/ml) 500 IU/h over seven hours. No other heparin product (including arteria flush lines) nor dilution fluids at the dialyzer are allowed during the study period of 24 hours. Each SLEDD treatment will be performed with Cordiax 5008S (Fresenius) for 8 hours. After the study period of 24 hours thromboprophylaxis will be prescribed according to the normal practice in the ICU.

The primary outcome measure is plasma anti-FXa concentration at 4 hours from the onset of SLEDD. Plasma Anti-FXa will be drawn at timepoints 0 hours, 4 hours, 8 hours and 24 hours from the onset of the dialysis.

The clotting formation in RRT system will be evaluated by clotting scoring. In the case of serious clotting RRT treatment is stopped and the new RRT is started. The study will end to the new RRT.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anne Kuitunen, MD, PhD; Phone Number: +358331165544; Email: anne.kuitunen@pshp.fi
• Study Contact Backup: Name: Simo Varila; Phone Number: +358505128189; Email: simo.varila@pshp.fi

Study Locations

• Finland
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33521
      • Recruiting
      • Tampere University Hospital
      • Contact: Anne Kuitunen, PhD; Phone Number: +358 3 311 65544; Email: anne.kuitunen@pshp.fi
      • Sub-Investigator: Annukka Vahtera, MD
      • Sub-Investigator: Ville Jalkanen, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Critically ill patients requiring intensive care
• Indication for pharmacological thromboprophylaxis
• Written informed consent obtained from the patient or his/her legal representative
• Indication for SLEDD, any of following:
• serum creatinine concentration of more than 354 micromol/l or greater than 3 times the baseline creatinine level OR
• anuria (urine output of 100 ml/day) for more than 12 hours OR
• oliguria: below 0.3 ml/kg/h for more than 24 hours OR 500 ml/day
• the presence of clinically significant organ edema (e.g., pulmonary edema, elevated intra-abdominal pressure, significant peripheral swelling) together with oliguria or anuria
• Dialysis dependence after continuous renal replacement treatment

Exclusion Criteria:

• Other indications for anticoagulant therapy than thromboprophylaxis (including sodium citrate for CRRT)
• Any long-term anticoagulant or antithrombotic medication, except for low-dose aspirin (<150 mg daily)
• Treatment with tinzaparin or any other LMWH or heparin within 24 hours of study inclusion
• Known heparin induced thrombocytopenia (HIT), or hypersensitivity to tinzaparin or any other heparin
• Known pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Bolus of 4500 IU tinzaparin	Drug: Tinzaparin bolus; 4500 IU bolus of Tinzaparin
Active Comparator: Study group; Bolus of 4500 IU tinzaparin and continuous infusion of 4500 IU tinzaparin	Drug: Tinzaparin bolus; 4500 IU bolus of Tinzaparin; Drug: Tinzaparin continuous infusion; 4500 IU continuous infusion of Tinzaparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma anti-FXa concentration	Plasma anti-factor Xa blood sample	4 hours from the onset of SLEDD

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma anti-FXa concentration	Plasma anti-factor Xa blood sample	8 hours from the onset of SLEDD
Plasma anti-FXa concentration	Plasma anti-factor Xa blood sample	24 hours from the onset of SLEDD
Clotting Score	Clotting in renal replacement sircuit will be evaluated hourly according to predescribed score	8 hours from the onset of SLEDD

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Investigators: Principal Investigator: Anne Kuitunen, MD, PhD, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: July 30, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: R18098M

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No