Clinical Trial to Evaluate the Accuracy of [99mTc] ThromboView in the Detection of Deep Vein Thrombosis

Overview

The assessment of patients with suspected deep vein thrombosis (DVT) is a common clinical scenario that, despite major advances in diagnostic testing, continues to be challenging. The diagnosis of DVT remains problematic in: * patients with suspected first DVT who have a moderate or high pre-test probability (PTP) for DVT and a normal compression ultrasound (CUS); * patients with suspected recurrent DVT; and * patients in whom CUS or contrast venography is technically difficult or not feasible due to patient characteristics. In patients with suspected first DVT who have a moderate or high PTP and a normal CUS, DVT occurs in up to 10% of cases. Thus, additional diagnostic testing is required, such as venography or serial CUS, so that DVT is not missed, but these approaches are costly and invasive. In patients with suspected recurrent DVT, currently used diagnostic approaches are problematic because they all have limitations in differentiating old disease from true recurrent disease. CUS is technically difficult in selected patients, particularly those who are obese. Contrast venography is the gold standard diagnostic test for DVT to which all other diagnostic venous imaging modalities for DVT are compared and judged. The Food and Drug Administration (FDA) requires that a new diagnostic test for DVT be assessed against venography. \[99mTc\] ThromboView® is a novel diagnostic test based on a 99mTc-labeled monoclonal antibody specific for D-dimer fragments of cross-linked fibrin that are found in acute DVT. After intravenous injection of \[99mTc\] ThromboView®, there is uptake of the monoclonal antibody by acute, D-dimer rich, venous thrombi. This is visualized with nuclear medicine imaging as an area of increased radioisotope activity that corresponds to the location of DVT. Based on the biologic and imaging characteristics of \[99mTc\] ThromboView®, this diagnostic test has the potential to: * identify small non-occlusive proximal DVT or distal DVT in patients with a moderate or high PTP and normal CUS; * differentiate old from new DVT in patients with suspected recurrent DVT; * diagnose or exclude DVT in patients in whom CUS is not technically feasible; and * provide an alternative to venography that is non-invasive, has no contrast-related toxicity and is easily administered. The present study is the first phase II clinical trial of \[99mTc\] ThromboView® in patients with suspected initial or recurrent DVT in whom DVT has been confirmed or excluded by venography. A phase II clinical trial to investigate the diagnostic accuracy of \[99mTc\] ThromboView® is justified because: * ThromboView® was well tolerated, with no significant toxicity in studies involving animals and healthy volunteers; and * it has shown promise in Phase I trials as a non-invasive diagnostic test for acute DVT.