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Thromb Haemost 2003; 90(02): 252-259
DOI: 10.1160/TH02-09-0061
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Fixed-dose, body weight-independent subcutaneous low molecular weight heparin Certoparin compared with adjusted-dose intravenous unfractionated heparin in patients with proximal deep venous thrombosis

for the TH-4Study Group
Hanno Riess
1   Medical Clinic, Charité University Clinic, Campus Virchow Clinic, Berlin, Germany
,
Klaus Koppenhagen
2   University Clinic Benjamin Franklin, Berlin, Germany
,
Alexander Tolle
3   Novartis Pharma GmbH, Nuremberg, Germany
,
Bettina Kemkes-Matthes
4   Medical Clinic, Justus Liebig University, Giessen, Germany
,
Michael Gräve
3   Novartis Pharma GmbH, Nuremberg, Germany
,
Frantisek Patek
5   Masarykova Nemocnice, Ústí nad Labem, The Czech Republic
,
Michael Drexler
6   St Josef’s Hospital, Wiesbaden, Germany
,
Hans-Joachim G. Siemens
7   Medical Clinic, University of Lubeck, Germany
,
Job Harenberg
8   Medical Clinic, University Clinic, Mannheim, Germany
,
Gottfried Weidinger
3   Novartis Pharma GmbH, Nuremberg, Germany
,
Joachim Brom
3   Novartis Pharma GmbH, Nuremberg, Germany
,
Sylvia Haas
9   Department of Experimental Oncology and Therapeutic Research, Technical University Munich, Germany
› Author AffiliationsFinancial support: The study was supported by Novartis Pharma GmbH, Nuremberg, Germany. The results of the study were presented in part at the 42nd Annual Meeting of the American Society of Hematology, San Francisco, CA, December 04, 2000 and the XVIIIth Congress of the International Society on Thrombosis and Haemostasis, Paris, France, July 10, 2001.
Further Information

Publication History

Received 12 September 2003

Accepted after revision 12 May 2003

Publication Date:
06 December 2017 (online)

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Summary

Subcutaneous body weight-adjusted low molecular weight heparin (LMWH) has been proven as effective and safe as intravenous aPTT-adjusted unfractionated heparin (UFH) for the treatment of patients with acute deep venous thrombosis (DVT). In this study we evaluate the efficacy of the initial treatment of proximal DVT with a fixed-dose, body weight-independent application of the LMWH Certoparin with a six month follow-up.

In a prospective, multicentre, randomized, active-controlled study 1220 patients with objectively diagnosed proximal DVT were randomly assigned to subcutaneous 8000 U anti-factor Xa of Certoparin twice daily for 10 to 14 days or intravenous aPTT-adjusted UFH for 5 to 8 days. Both regimen were followed by oral anticoagulation for 6 months. The primary end point was the rate of symptomatic and objectively confirmed thromboembolic events within 6 months. The aim of the study was to demonstrate the non-inferiority of the Certoparin regimen as compared to UFH.

The per-protocol analysis revealed 22 (3.8%) thromboembolic events in the Certoparin group and 24 (4.3%) in patients assigned to UFH within 6 months, thereby proving the non-inferiority (p<0.01), confirmed by intent-to-treat analysis (p<0.001). Major bleeding occurred in 6 and 7 patients started on Certoparin or UFH during the treatment period. Thromboembolic events were equally distributed in body weight categories with < 50,50-80 and >80 kg as followed:0,3.6% and 4.1% of patients for the Certoparin group and 0, 4.6% and 4.2% of patients for the UFH group. The same was true for major bleeding complications with 0, 2.9% and 1.5% for Certoparin and 0, 3.5% and 4.2% for UFH. Overall mortality was 1.9 % in the Certoparin group and 2.7 % in the UFH group.

Fixed-dose body weight-independent subcutaneous LMWH Certoparin is at least as efficacious and safe as intravenous aPTT-adjusted UFH for the initial treatment of acute proximal DVT. This effect is maintained during a 6-months follow-up of treatment with oral anticoagulation.

Keywords

Deep venous thrombosis - therapy - low molecular weight heparin
 

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