Norwegian Intensive Care Unit Dalteparin Effect Study (NORIDES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Oslo University Hospital
Sponsor:
Collaborator:
University of Oslo
Information provided by (Responsible Party):
Sigrid Beitland, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT01721928
First received: October 26, 2012
Last updated: January 3, 2013
Last verified: January 2013
  Purpose

The main purpose of the NORIDES study is to investigate the effect of pharmacological thromboprophylaxis with low molecular weight heparins (LMWHs) in critically ill patients, and how it is affected by presence of acute kidney injury (AKI) and treatment with hemodialysis. The main objective is to compare the prophylactic effect of dalteparin in intensive care unit (ICU) patients with AKI and Citrate-Calcium dialysis (CiCa-dialysis) with a control group of ICU patients with normal kidney function. Our main hypothesis is that CiCa-dialysis reduces dalteparin effect, and that patients undergoing CiCa-dialysis do not achieve adequate prophylaxis against venous thromboembolism (VTE). The primary endpoint is development of DVT during ICU stay, the secondary endpoint inadequate heparin effect measured in blood samples.


Condition Intervention
Acute Kidney Injury
Deep Venous Thrombosis
Device: Continuous venovenous hemodialysis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Norwegian Intensive Care Unit Dalteparin Effect Study

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • The primary endpoint is development of deep venous thrombosis (DVT) [ Time Frame: Twice a week until ICU LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Screening for DVT using DUS of both upper- and lower extremities will be performed within 48 hours after ICU admission and thereafter twice a week until discharge from ICU or ICU stay equal to 30 days. An additional DUS will be performed 3 months after ICU discharge.


Secondary Outcome Measures:
  • The secondary endpoint is inadequate heparin effect measured in blood samples [ Time Frame: Blood samples is drawn 4 times during ICU stay, from minimum day 2 to maximum day 30 dependent on the dialysis therapy ] [ Designated as safety issue: No ]
    Blood samples will be drawn from intravasal catheters (preferably arterial, alternatively central venous) to examine heparin effect (anti-Xa activity, TGA and TEG) and other haematological analyses including antithrombin concentrations. Whole blood will be drawn on two separate days immediately before and 4 hours after dalteparin administration in order to measure tough and peak effect of heparin. Dalteparin effect in ICU patients undergoing dialysis therapy will be measured one day with and one day without ongoing dialysis therapy in order to distinguish the effect of AKI from the effect of CRRT.


Other Outcome Measures:
  • Which of the blood sample analyses anti-Xa activity, TEG or TGA is superior in detecting critically ill patients who will subsequently develop DVT? [ Time Frame: Whole blood will be drawn on two separate days from minimum day 2 to maximum day 30 dependent on the dialysis therapy, immediately before and 4 hours after dalteparin administration in order to measure tough and peak effect of heparin. ] [ Designated as safety issue: No ]
    The blood sample analyses anti-Xa activity, TEG and TGA will be analysed, and their ability to detect critically ill patients who will subsequently develop DVT. Different patients with and without AKI will be compared. Samples from the same patients one day with and one day without dialysis therapy will also be compared.

  • Which factors affect heparin effect in critically ill patients? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    The following factors will be assessed: Presence of AKI, dialysis therapy, Body mass index (BMI), gender, high severity of illness, use of vasopressors, presence of oedema and serum antithrombin concentrations.

  • What is the incidence of DVT and bleeding in ICU patients with and without CiCa-dialysis therapy, and is it correlated to heparin effect? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Compare the incidence of DVT and bleeding among ICU patients with and without CiCa-dialysis. Investigate if patient with bleeding have different anti-Xa activity levels, TGA and TEG than patients without bleeding, and if patients with DVT have different anti-Xa activity levels, TGA and TEG compared to patients without DVT.

  • Do ICU patients with AKI treated with CRRT have lower blood flow to the kidneys measured as renal perfusion index during contrast enhanced DUS compared to similar ICU patients without AKI? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Blood flow to the kidneys measured as renal perfusion index during contrast enhanced DUS will be compared in selected ICU patients with and without CRRT.

  • Is the renal blood flow measured as renal perfusion index during contrast enhanced DUS correlated to a global blood flow measured as cardiac index using PICCO®? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Blood flow to the kidneys measured as renal perfusion index during contrast enhanced DUS will be compared with global perfusion measured as cardiac index using a pulse contour analysis device (PICCO®).

  • Is examination of patient urine using Nuclear Magnetic Resonance (NMR) spectroscopy different in ICU patient with and without AKI and what is the effect of CiCa-dialysis on NMR spectroscopy? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    NMR spectroscopy of urine in ICU patients with and without AKI necessitating CRRT will be compared, and levels in the same patients with and without dialysis therapy. Further, NMR spectroscopy of urine in the same patient with and without dialysis therapy will be compared.

  • Which bedside method is superior in predicting dialysis circuit clotting? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Collect data on filter clotting. Evaluate the predictive value of different bedside methods clinically used to forecast filter clotting: Post filter ionised calcium, heparin-active R-time during TEG, access pressure, filter pressure, return pressure and visual inspection of the dialysis circuit air trap.

  • Which factors affects filter lifetime during CiCa-dialysis? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Collect data on filter lifetime during CiCa-dialysis therapy and investigate if there is a correlation between measured filter lifetime and the following factors: Heparin effect, antithrombin levels, post filter ionised calcium, NMR spectroscopy of urine, clinical assessment of clotting as well as anatomical placement of the dialysis catheter.

  • Which risk factors for DVT are present in an ICU population and what is the contribution of each factor in development of DVT? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Prospective collection of data on risk factor for DVT in an ICU population according to international guidelines. Also screening for DVT in an ICU population using DUS. Thereafter we plan to perform an analysis on the contribution of each risk factor and combinations of risk factors on development of DVT, with special attention towards possible avoidable risk factors.

  • Is the presence of DVT in ICU patients influenced by the anatomical placement of catheters such as central venous catheters (CVCs) and dialysis catheters? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    Compare the incidence of catheter related DVT if CVC and dialysis catheters are placed in the femoral, subclavian and internal jugular veins.

  • Does the presence of DVT influence the prognosis in ICU patients? [ Time Frame: Data will be collected during ICU stay until LOS 30 days or discharge from ICU. Mortality will also be assessed after ICU discharge. ] [ Designated as safety issue: No ]
    To compare preset prognostic markers for morbidity (ICU and hospital length of stay in addition to time on ventilator and dialysis therapy) and mortality (ICU mortality and 30 days mortality) in patients with and without presence of DVT.

  • Does metabolic alkalosis due to CiCa-dialysis therapy lead to prolonged ventilator therapy? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    To compare arterial blood gases in ICU patients with and without CiCa-dialysis and evaluate if patients treated with dialysis more often have metabolic alkalosis. Further, to study whether there is an association between presence of metabolic alkalosis and time spent on ventilator therapy.

  • What is the compliance to our clinical practice guidelines for thromboprophylaxis in the ICU, and does low compliance to guidelines lead to more frequent DVT? [ Time Frame: During ICU stay until LOS 30 days or discharge from ICU ] [ Designated as safety issue: No ]
    To compare occurrence of DVT and its correlation to compliance to clinical practice guidelines for DVT prophylaxis, including pharmacological and non-pharmacological prophylaxis.

  • What is the occurrence of DVT 3 months after ICU discharge? [ Time Frame: Patients will be screened for DVT 3 months after ICU discharge. ] [ Designated as safety issue: No ]
    To find the occurrence of DVT in critically ill patients 3 months after ICU discharge. Survivors who did not develop DVT during ICU stay will be screened for DVT after 3 months using DUS examination.

  • Future blood and urine analyses of ICU patients with and without AKI and dialysis therapy. [ Time Frame: Blood and urine samples will be collected during ICU stay until LOS 30 days or discharge from ICU. The samples will be stored for future analysis with a maximum of 10 years storage. ] [ Designated as safety issue: No ]
    To compare blood and urine samples from critically ill patients with and without AKI and dialysis therapy. The blood and urin samples can be stored for maximum 10 years. The plan is to use new, yet not known analysis methods, and test their utility when assessing ICU patients with and without AKI and dialysis therapy.


Biospecimen Retention:   Samples Without DNA

12 ml whole blood (10 ml for storage and 2 ml for bedside TEG analysis) will be aspirated from the arterial or the central venous catheter for each measurement. Four measurements will be performed in each patient, from minimum day 2 to maximum day 30 dependent on the dialysis therapy.

Four urinary samples (each of 20 ml) will be collected from urinary catheter collection bags at the same time as blood samples are drawn.

Blood (20 mL stored as whole blood, serum and plasma) and urine samples (20 mL) will be collected from each patient at the same time as blood samples are drawn. The samples will be stored at - 70°C for future analysis.


Estimated Enrollment: 300
Study Start Date: November 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
ICU patients with AKI
ICU patients with AKI treated with continuous venovenous hemodialysis
Device: Continuous venovenous hemodialysis
Continuous venovenous hemodialysis
Other Names:
  • CVVHD
  • CRRT
ICU patients without AKI
ICU patients without AKI defined as RIFLE group O and R

Detailed Description:

Description of deep venous thrombosis (DVT) diagnosis: Screening for DVT using Doppler Ultrasound (DUS) of both upper- and lower extremities will be performed within 48 hours after ICU admission and thereafter twice a week until discharge from ICU or ICU stay equal to 30 days. An additional DUS will be performed 3 months after ICU discharge.

Description of heparin effect measured in blood samples: Blood samples will be drawn from intravasal catheters (preferably arterial, alternatively central venous) to examine heparin effect (anti-Xa activity, thrombin generation assay (TGA) and thrombelastography (TEG) and other haematological analyses including antithrombin concentrations. Whole blood will be drawn on two separate days (from minimum day 2 to maximum day 30 dependent on the dialysis therapy) of ICU stay immediately before and 4 hours after dalteparin administration in order to measure tough and peak effect of heparin. Dalteparin effect in ICU patients undergoing dialysis therapy will be measured one day with and one day without ongoing dialysis therapy in order to distinguish the effect of AKI from the effect of continuous renal replacement therapy (CRRT).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The main objective is to compare the prophylactic effect of dalteparin in intensive care unit patients with acute kidney injury and continuous renal replacement therapy with a control group of intensive care unit patients with normal kidney function.

Criteria

Inclusion Criteria:

  • ICU patients receiving prophylactic dalteparin

Exclusion Criteria:

  • Age < 18 years
  • Intraocular bleeding
  • Intracranial bleeding
  • Acute spinal cord lesion
  • Inherited coagulopathy
  • Ongoing, uncontrolled bleeding
  • Therapeutic anticoagulation
  • Uncorrected coagulopathy
  • Pregnancy or postpartum < 6 weeks
  • Patient weight < 50 kg or > 100 kg
  • Participation in an interventional study
  • RIFLE class E
  • Consent not received
  • ICU length of stay less than 48 hours
  • DVT detected at first DUS examination
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01721928

Contacts
Contact: Sigrid Beitland, MD +4722117387 ext No sigrid.beitland@medisin.uio.no
Contact: Kjetil Sunde, Professor +4722119585 ext No kjetil.sunde@medisin.uio.no

Locations
Norway
Oslo University Hospital Recruiting
Oslo, Norway, 0540
Contact: Sigrid Beitland, MD    +4722117387    sigrid.beitland@medisin.uio.no   
Contact: Kjetil Sunde, Pofessor    +4722119585    kjetil.sunde@medisin.uio.no   
Principal Investigator: Sigrid Beitland, MD         
Sub-Investigator: Kjetil Sunde, Professor         
Sponsors and Collaborators
Oslo University Hospital
University of Oslo
Investigators
Study Chair: Kjetil Sunde, Professor Oslo University Hospital
Principal Investigator: Sigrid Beitland, MD Oslo University Hospital
Study Director: Per M Sandset, Professor Oslo University Hospital
  More Information

Publications:

Responsible Party: Sigrid Beitland, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT01721928     History of Changes
Other Study ID Numbers: 2012/942, UiO
Study First Received: October 26, 2012
Last Updated: January 3, 2013
Health Authority: Norway: Regional Ethics Commitee
Norway: Data Protection Authority

Keywords provided by Oslo University Hospital:
Acute kidney injury
Deep venous thrombosis
Dialysis
Prophylaxis

Additional relevant MeSH terms:
Acute Kidney Injury
Thrombosis
Venous Thrombosis
Venous Thromboembolism
Wounds and Injuries
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thromboembolism
Dalteparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 24, 2014