Accumulation of Nadroparin Used in Renal Insufficiency Assessed by anti-Xa levels.

Rationale:

Prevention and treatment of venous thromboembolism (VTE) with low-molecular-weight heparins (LMWHs) is confirmed to be at least as effective as with unfractionated heparin (UFH). In comparison to UFH, the LMWHs have improved pharmacokinetics, ease of administration and lack of need of laboratory monitoring, which has greatly increased the use of LMWHs. Because the elimination of LMWHs is mainly determined by renal excretion, the use of LMWHs in patients with renal insufficiency might lead to accumulation of the drug, accompanied by an increase in anti-Xa level and thereby a greater risk for hemorrhagic complications. In literature, data are available on accumulation of LMWHs in patients with renal insufficiency. However, the rate of accumulation of LMWHs and implications for the dosing regimen of LMWHs is only established in one study previously (Mismetti et al. Aging and Venous Thromboembolism Influence the Pharmacodynamics of the Anti-Factor Xa and Anti-thrombin Activities of a Low Molecular Weight Heparin (Nadroparin). Thromb Haemost 1998; 79: 1162-1165). In this study we investigate the accumulation of nadroparin used in renal insufficiency assessed by anti-Xa levels.



Objective:

The aim of this study is to determine the accumulation of nadroparin used in renal insufficient patients with VTE, by measuring anti-Xa levels.



Study design:

Prospective, observational, follow-up study.



Study population:

Hospitalised adult patients with VTE and renal insufficiency (defined as a glomerular filtration rate (GFR) of less than 50 ml/min) to whom subcutaneous nadroparin is administered on general medical or surgical departments of the Erasmus MC in Rotterdam, the Netherlands.



Main study parameters/endpoints:

Anti-Xa levels will be measured 4 hours (± 1 hour) after subcutaneous injection of nadroparin on day 1, day 3 and day 5 of treatment. Primary outcome is the degree of accumulation, defined as the percentage of increase of anti-Xa level on day 5 compared to day 1. This primary outcome will be assessed for various levels of renal function. Secondary endpoints are the percentage of increase of anti-Xa level on day 3 compared to day 1 and bleeding complications during treatment with nadroparin.



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The patient will be asked for 3 blood samples of 4.5 ml to measure the anti-Xa level during treatment with nadroparin. Standard care will be provided, so if the doctor does not decide to measure anti-Xa himself, then the anti-Xa analyses will take place in batches after day 5 of treatment with nadroparin (and thus the values will not be used to adjust therapy during the study period). If still relevant (i.e. when nadroparin is still in use) the anti-Xa levels will be communicated to the doctor after day 5.

Prevention and treatment of venous thromboembolism (VTE) with low-molecular-weight heparins (LMWHs) is confirmed to be at least as effective as with unfractionated heparin (UFH). In comparison to UFH, the LMWHs have improved pharmacokinetics, ease of administration and lack of need of laboratory monitoring, which has greatly increased the use of LMWHs. Because the elimination of LMWHs is mainly determined by renal excretion, the use of LMWHs in patients with renal insufficiency might lead to accumulation of the drug, accompanied by an increase in anti-Xa level and thereby a greater risk for hemorrhagic complications. In literature, data are available on accumulation of LMWHs in patients with renal insufficiency. However, the rate of accumulation of LMWHs and implications for the dosing regimen of LMWHs is still unclear. In this study we investigate the accumulation of nadroparin used in renal insufficiency assessed by anti-Xa levels.

Day 1, day 3 and day 5 of treatment with nadroparin.

No interventions will be done, as this is an observational study.