Norwegian Intensive Care Unit Dalteparin Effect Study

NCT01721928 | Completed

• 2 other identifiers: 2012/942UiO
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Kidney Injury; Deep Venous Thrombosis

Keywords

Acute kidney injury; Deep venous thrombosis; Dialysis; Prophylaxis

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is development of deep venous thrombosis (DVT)

  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.

  Twice a week until ICU LOS 30 days or discharge from ICU

Secondary Outcomes (1)

• The secondary endpoint is inadequate heparin effect measured in blood samples

  Blood samples is drawn 4 times during ICU stay, from minimum day 2 to maximum day 30 dependent on the dialysis therapy

Other Outcomes (15)

• Which of the blood sample analyses anti-Xa activity, TEG or TGA is superior in detecting critically ill patients who will subsequently develop DVT?

  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.

• Which factors affect heparin effect in critically ill patients?

  During ICU stay until LOS 30 days or discharge from ICU

• What is the incidence of DVT and bleeding in ICU patients with and without CiCa-dialysis therapy, and is it correlated to heparin effect?

  During ICU stay until LOS 30 days or discharge from ICU

Study Arms (2)

ICU patients with AKI

ICU patients with AKI treated with continuous venovenous hemodialysis

Device: Continuous venovenous hemodialysis

ICU patients without AKI

ICU patients without AKI defined as RIFLE group O and R

Interventions

Continuous venovenous hemodialysis DEVICE

Continuous venovenous hemodialysis

Also known as: CVVHD, CRRT

ICU patients with AKI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• ICU patients receiving prophylactic dalteparin

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Oslo University Hospital: lead
• University of Oslo: collaborator

Study Sites (1)

Oslo University Hospital

Oslo, 0540, Norway

Location

Related Publications (29)

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  PMID: 16552665 BACKGROUND

• Cook DJ, Douketis J, Arnold D, Crowther MA. Bleeding and venous thromboembolism in the critically ill with emphasis on patients with renal insufficiency. Curr Opin Pulm Med. 2009 Sep;15(5):455-62. doi: 10.1097/MCP.0b013e32832ea4dd.

  PMID: 19617833 BACKGROUND

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• Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):381S-453S. doi: 10.1378/chest.08-0656.

  PMID: 18574271 BACKGROUND

• Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, Wheeler HB. Prevention of venous thromboembolism. Chest. 2001 Jan;119(1 Suppl):132S-175S. doi: 10.1378/chest.119.1_suppl.132s. No abstract available.

  PMID: 11157647 BACKGROUND

• Leclerc JR, Gent M, Hirsh J, Geerts WH, Ginsberg JS. The incidence of symptomatic venous thromboembolism after enoxaparin prophylaxis in lower extremity arthroplasty: a cohort study of 1,984 patients. Canadian Collaborative Group. Chest. 1998 Aug;114(2 Suppl Evidence):115S-118S. doi: 10.1378/chest.114.2_supplement.115s. No abstract available.

  PMID: 9726704 BACKGROUND

• Ribic C, Lim W, Cook D, Crowther M. Low-molecular-weight heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review. J Crit Care. 2009 Jun;24(2):197-205. doi: 10.1016/j.jcrc.2008.11.002. Epub 2009 Feb 7.

  PMID: 19327323 BACKGROUND

• Spyropoulos AC, Anderson FA Jr, FitzGerald G, Decousus H, Pini M, Chong BH, Zotz RB, Bergmann JF, Tapson V, Froehlich JB, Monreal M, Merli GJ, Pavanello R, Turpie AGG, Nakamura M, Piovella F, Kakkar AK, Spencer FA; IMPROVE Investigators. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011 Sep;140(3):706-714. doi: 10.1378/chest.10-1944. Epub 2011 Mar 24.

  PMID: 21436241 BACKGROUND

• Khouli H, Shapiro J, Pham VP, Arfaei A, Esan O, Jean R, Homel P. Efficacy of deep venous thrombosis prophylaxis in the medical intensive care unit. J Intensive Care Med. 2006 Nov-Dec;21(6):352-8. doi: 10.1177/0885066606292880.

  PMID: 17095499 BACKGROUND

• Rabbat CG, Cook DJ, Crowther MA, McDonald E, Clarke F, Meade MO, Lee KA, Cook RJ. Dalteparin thromboprophylaxis for critically ill medical-surgical patients with renal insufficiency. J Crit Care. 2005 Dec;20(4):357-63. doi: 10.1016/j.jcrc.2005.09.009.

  PMID: 16310608 BACKGROUND

• Crowther MA, Cook DJ, Griffith LE, Devereaux PJ, Rabbat CC, Clarke FJ, Hoad N, McDonald E, Meade MO, Guyatt GH, Geerts WH, Wells PS. Deep venous thrombosis: clinically silent in the intensive care unit. J Crit Care. 2005 Dec;20(4):334-40. doi: 10.1016/j.jcrc.2005.09.011.

  PMID: 16310604 BACKGROUND

• Douketis JD, Rabbat C, Crowther MA; VTE in the ICU Workshop Participants. Anticoagulant prophylaxis in special populations with an indwelling epidural catheter or renal insufficiency. J Crit Care. 2005 Dec;20(4):324-9. doi: 10.1016/j.jcrc.2005.09.001.

  PMID: 16310603 BACKGROUND

• Cook D, Crowther MA, Douketis J; VTE in the ICU Workshop Participants. Thromboprophylaxis in medical-surgical intensive care unit patients. J Crit Care. 2005 Dec;20(4):320-3. doi: 10.1016/j.jcrc.2005.09.007. No abstract available.

  PMID: 16310602 BACKGROUND

• Cook D, Douketis J, Crowther MA, Anderson DR; VTE in the ICU Workshop Participants. The diagnosis of deep venous thrombosis and pulmonary embolism in medical-surgical intensive care unit patients. J Crit Care. 2005 Dec;20(4):314-9. doi: 10.1016/j.jcrc.2005.09.003. No abstract available.

  PMID: 16310601 BACKGROUND

• Cook DJ, Crowther MA, Meade MO, Douketis J; VTE in the ICU Workshop Participants. Prevalence, incidence, and risk factors for venous thromboembolism in medical-surgical intensive care unit patients. J Crit Care. 2005 Dec;20(4):309-13. doi: 10.1016/j.jcrc.2005.09.005. No abstract available.

  PMID: 16310600 BACKGROUND

• Cook DJ, Crowther MA, Geerts WH. On the need for a workshop on venous thromboembolism in critical care. J Crit Care. 2005 Dec;20(4):306-8. doi: 10.1016/j.jcrc.2005.09.004. No abstract available.

  PMID: 16310599 BACKGROUND

• Swarczinski C, Dijkers M. The value of serial leg measurements for monitoring deep vein thrombosis in spinal cord injury. J Neurosci Nurs. 1991 Oct;23(5):306-14. doi: 10.1097/01376517-199110000-00007.

  PMID: 1835995 BACKGROUND

• Makris PE, Pithara E. Clinical evaluation of new global clotting assay for monitoring of LMWH treatment: pilot study. Int Angiol. 1998 Jun;17(2):69-79.

  PMID: 9754892 BACKGROUND

• Haas FJ, Kluft C, Biesma DH, Schutgens RE. Patients with deep venous thrombosis and thrombophilia risk factors have a specific prolongation of the lag time in a chromogenic thrombin generation assay. Blood Coagul Fibrinolysis. 2011 Sep;22(6):506-11. doi: 10.1097/MBC.0b013e328347404d.

  PMID: 21537160 BACKGROUND

• Marik PE, Andrews L, Maini B. The incidence of deep venous thrombosis in ICU patients. Chest. 1997 Mar;111(3):661-4. doi: 10.1378/chest.111.3.661.

  PMID: 9118705 BACKGROUND

• Cook DJ, Rocker G, Meade M, Guyatt G, Geerts W, Anderson D, Skrobik Y, Hebert P, Albert M, Cooper J, Bates S, Caco C, Finfer S, Fowler R, Freitag A, Granton J, Jones G, Langevin S, Mehta S, Pagliarello G, Poirier G, Rabbat C, Schiff D, Griffith L, Crowther M; PROTECT Investigators; Canadian Critical Care Trials Group. Prophylaxis of Thromboembolism in Critical Care (PROTECT) Trial: a pilot study. J Crit Care. 2005 Dec;20(4):364-72. doi: 10.1016/j.jcrc.2005.09.010.

  PMID: 16310609 BACKGROUND

• Patel R, Cook DJ, Meade MO, Griffith LE, Mehta G, Rocker GM, Marshall JC, Hodder R, Martin CM, Heyland DK, Peters S, Muscedere J, Soth M, Campbell N, Guyatt GH; Burden of Illness in venous ThromboEmbolism in Critical care (BITEC) Study Investigators; Canadian Critical Care Trials Group. Burden of illness in venous thromboembolism in critical care: a multicenter observational study. J Crit Care. 2005 Dec;20(4):341-7. doi: 10.1016/j.jcrc.2005.09.014.

  PMID: 16310605 BACKGROUND

• Crowther MA, Cook DJ, Griffith LE, Meade M, Hanna S, Rabbat C, Bates SM, Geerts W, Johnston M, Guyatt G. Neither baseline tests of molecular hypercoagulability nor D-dimer levels predict deep venous thrombosis in critically ill medical-surgical patients. Intensive Care Med. 2005 Jan;31(1):48-55. doi: 10.1007/s00134-004-2467-2. Epub 2004 Dec 9.

  PMID: 15592816 BACKGROUND

• Cook D, Meade M, Guyatt G, Griffith L, Granton J, Geerts W, Crowther M; Canadian Critical Care Trials Group. Clinically important deep vein thrombosis in the intensive care unit: a survey of intensivists. Crit Care. 2004 Jun;8(3):R145-52. doi: 10.1186/cc2859. Epub 2004 May 6.

  PMID: 15153243 BACKGROUND

• Malinoski D, Jafari F, Ewing T, Ardary C, Conniff H, Baje M, Kong A, Lekawa ME, Dolich MO, Cinat ME, Barrios C, Hoyt DB. Standard prophylactic enoxaparin dosing leads to inadequate anti-Xa levels and increased deep venous thrombosis rates in critically ill trauma and surgical patients. J Trauma. 2010 Apr;68(4):874-80. doi: 10.1097/TA.0b013e3181d32271.

  PMID: 20386282 BACKGROUND

• Malinoski D, Ewing T, Patel MS, Jafari F, Sloane B, Nguyen B, Barrios C, Kong A, Cinat M, Dolich M, Lekawa M, Hoyt DB. Risk factors for venous thromboembolism in critically ill trauma patients who cannot receive chemical prophylaxis. Injury. 2013 Jan;44(1):80-5. doi: 10.1016/j.injury.2011.10.006. Epub 2011 Nov 1.

  PMID: 22047757 BACKGROUND

• Van PY, Cho SD, Underwood SJ, Morris MS, Watters JM, Schreiber MA. Thrombelastography versus AntiFactor Xa levels in the assessment of prophylactic-dose enoxaparin in critically ill patients. J Trauma. 2009 Jun;66(6):1509-15; discussion 1515-7. doi: 10.1097/TA.0b013e3181a51e33.

  PMID: 19509608 BACKGROUND

• Klein SM, Slaughter TF, Vail PT, Ginsberg B, El-Moalem HE, Alexander R, D'Ercole F, Greengrass RA, Perumal TT, Welsby I, Gan TJ. Thromboelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: a comparison with anti-Xa concentrations. Anesth Analg. 2000 Nov;91(5):1091-5. doi: 10.1097/00000539-200011000-00009.

  PMID: 11049889 BACKGROUND

• Schleyer AM, Schreuder AB, Jarman KM, Logerfo JP, Goss JR. Adherence to guideline-directed venous thromboembolism prophylaxis among medical and surgical inpatients at 33 academic medical centers in the United States. Am J Med Qual. 2011 May-Jun;26(3):174-80. doi: 10.1177/1062860610382289. Epub 2011 Apr 13.

  PMID: 21490270 BACKGROUND

Biospecimen

Retention: SAMPLES WITH 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.

MeSH Terms

Conditions

Acute Kidney Injury; Venous Thrombosis

Interventions

Continuous Renal Replacement Therapy

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Kjetil Sunde, Professor

  Oslo University Hospital

  STUDY CHAIR

• Sigrid Beitland, MD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Per M Sandset, Professor

  Oslo University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oslo University Hospital

Study Record Dates

• First Submitted: October 26, 2012
• First Posted: November 6, 2012
• Study Start: December 3, 2012
• Primary Completion: June 2, 2016
• Study Completion: March 1, 2017
• Last Updated: December 12, 2017

Record last verified: 2017-12

Locations

NO (1)