Randomised Long-Term Comparison of Tinzaparin and Dalteparin in Haemodialysis (original) (raw)

Abstract

Objective and design

Tinzaparin and dalteparin are low molecular weight heparins (LMWHs) with different pharmacokinetic and pharmacodynamic profiles that may lead to differences in efficacy and safety. In a long-term, multicentre, prospective, randomised trial we compared the efficacy and safety profiles of tinzaparin and dalteparin (starting doses were adjusted to comparable anti-IIa activity). The sample size was calculated to show a relative difference of 50% in unsatisfactory dialyses with a power of 80% (to prove superiority).

Patients

159 patients undergoing chronic intermittent haemodialysis were included in the study.

Main outcome measures

Efficacy was assessed by scoring the dialyser (from 1 = good, clear dialyser to 4 = total clotting of the dialyser requiring a change of the extracorporeal circuit) and bubble catcher (from 1 = no clots to 4 = severe clotting) after each dialysis. Levels of thrombin antithrombin complexes (TAT) were also determined. Safety was assessed by noting all minor and major bleeding.

Results

The mean anticoagulant dose for tinzaparin during the maintenance phase was about 10% lower than that of dalteparin: 5024 ± 2321 (range 700–12000) anti-Xa IU and 5546 ± 2395 (1875–12913) anti-Xa IU, respectively. No difference was found between treatments in clotting for either the dialyser or the bubble catcher (p = 0.59). TAT levels showed no difference between tinzaparin and dalteparin. The number of minor bleeds did not differ between treatments: 1.5% (40/2629 dialyses) for tinzaparin and 1.4% (41/2863 dialyses) for dalteparin, and one major bleed occurred in each treatment arm.

Conclusions

Dose calculation of tinzaparin and dalteparin according to anti-IIa activity resulted in equivalent efficacy and safety, although this was achieved with a 10% lower dose of tinzaparin measured in anti-Xa IU. Both LMWHs can be safely administered over a wide dosage range in patients undergoing long-term intermittent haemodialysis.

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Notes

  1. 1The use of tradenames is for product identification only and does not imply endorsement.

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Acknowledgements

This study was made possible by funding from LEO Pharma.

Study centres and participants: Diatel and Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands: R.J.R. Beijering, P. Stevens, J.W. ten Cate; Department of Nephrology, Gent, Belgium: R. Vanholder, A. Dhondt; Department of Nephrology, Haarlem, The Netherlands: W.T. van Dorp, N.H. Schut; Department of Nephrology, Uppsala, Sweden: B. Wikström; Department of Internal Medicine, Eskilstuna, Sweden: K.C. Gröntoft; Department of Internal Medicine, Trollhättan, Sweden: H. Mulec; Department of Internal Medicine, Örebro, Sweden: I. Andersen, P. Sjöström; Department of Internal Medicine, Gävle, Sweden: P. Halvarsson, U. Wrege.

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Authors and Affiliations

  1. Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Rolinda J. R. Beijering, Hugo ten Cate & Jan W. ten Cate
  2. Department of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Paul Stevens & Rudolf W. van Olden
  3. Department of Nephrology, Gent, Belgium
    Raymond Vanholder
  4. Department of Nephrology, Haarlem, The Netherlands
    Wim T. Van Dorp
  5. Department of Nephrology, Uppsala, Sweden
    Björn Wickström
  6. Medical Department, Critical Care, LEO Pharma, 55, Industriparken, Ballerup, DK, 2750, Denmark
    Per Sprøgel

Authors

  1. Rolinda J. R. Beijering
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  2. Hugo ten Cate
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  3. Paul Stevens
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  4. Raymond Vanholder
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  5. Wim T. Van Dorp
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  6. Rudolf W. van Olden
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  7. Björn Wickström
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  8. Per Sprøgel
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  9. Jan W. ten Cate
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Corresponding author

Correspondence to Per Sprøgel.

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Beijering, R.J.R., ten Cate, H., Stevens, P. et al. Randomised Long-Term Comparison of Tinzaparin and Dalteparin in Haemodialysis.Clin. Drug Invest. 23, 85–97 (2003). https://doi.org/10.2165/00044011-200323020-00002

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