PRANDONI

Low-molecular-weight heparin compared with standard heparin in proximal DVT (1992)

Condition

Initial treatment of acute proximal DVT in outpatients

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Objective

To compare the efficacy and safety of adjusted-dose intravenous standard heparin with those of fixed-dose subcutaneous low-molecular-weight heparin in the initial treatment of proximal DVT

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Trial design

Randomized, open study with parallel groups
Active treatment: nadroparin adjusted for the patient’s weight: 0.5, 0.6, or 0.7 ml s.c. twice daily in patients weighing <55, 55–80, or >80 kg, respectively (1.0 ml contains 25,400 anti factor Xa IU), given for 10 days, or longer if the INR was <2.0 (n=85)
Control treatment: UFH 100 IU/kg i.v. bolus, then 35,000 IU per 24 hours continuous i.v. infusion to target aPTT 1.5–2.0 times a control value, for 10 days or until INR >2.0 (n=85)

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Endpoints

Primary efficacy endpoints: recurrent symptomatic DVT (including symptomatic extension), and symptomatic PE during 6-month follow-up
Secondary efficacy endpoints: change in the extent of venous thrombosis between the day 10 and day 0 venograms; change in the number of segmental defects on the day 10 and day 0 perfusion lung scans
Primary safety endpoints: major bleeding during or within 48 hours of the end of heparin treatment

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Trial participants

170 consecutive symptomatic outpatients with venographically proven proximal DVT but no signs of PE

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Results

Efficacy outcome: During the 6-month follow-up, symptomatic recurrent VTE developed in 6 of the 85 patients assigned to nadroparin (7.1%) and in 12 of the 85 patients receiving standard heparin (14.1%). In the nadroparin group, there was a significantly lower rate of new segmental defects on lung scans compared with the standard-heparin group (5% vs. 19%; p<0.02). The changes in the extend of VTE on venography showed a significant difference in favor of nadroparin treatment (p=0.017)
Safety outcome: Major bleeding occurred during or within 48 hours of heparin treatment in 3 (3.5%) patients in the UFH group and in 1 (1.2%) patient in the nadroparin group. The frequency of minor bleeding was 7.1% and 2.3%, respectively. 12 (14.1%) patients in the standard-heparin group and 6 (7.1%) patients in the nadroparin group died during the 6-months study period

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Summary

Efficacy: Nadroparin was least as effective as standard heparin in the prevention of recurrent VTE. The greater efficacy of LMWH than of UFH is supported by the significantly lower rate of symptomless extension of thromboembolic disease found on posttreatment venograms and lung scans
Safety: Clinically important bleeding was infrequent in both treatment groups

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Reference

Prandoni P, Lensing AW, Büller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, ten Cate JW. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992;339:441-445

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Corresponding author

Anthonie W. A. Lensing, MD, Centre for Haemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Centre, F4-237, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands

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