Clinical Trial to Evaluate the Accuracy of [99mTc] ThromboView in the Detection of Deep Vein Thrombosis
Condition: Deep Vein Thrombosis
MeSH terms: Thrombosis; Venous Thrombosis
Intervention: ThromboView
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult man or woman, aged ≥18 years, presenting with suspected lower-limb initial or
             recurrent DVT.

          -  Moderate or high pre-test probability (PTP) for DVT.

          -  Onset of symptoms occurred within the last 7 days.

          -  Women of childbearing potential to have a negative pregnancy test as determined by
             measuring serum β-hCG levels at time of study enrolment.

        Exclusion Criteria:

          -  Receiving anticoagulant therapy at therapeutic doses for >3 days.

          -  Life expectancy <3 months.

          -  Patient with a renal transplant.

          -  Renal dysfunction: serum creatinine >1.5x upper limit of normal range.

          -  Hepatic dysfunction: serum transaminases >3x upper limit of normal range.

          -  Current pregnancy or lactation; or conception intended within 90 days of enrolment

          -  Of childbearing potential and unwilling to use adequate contraception for 30 days
             following enrolment

          -  Unable to undergo lower limb ascending venography on symptomatic leg(s).

          -  Allergy or other contraindication to intravenous contrast dye.

          -  Prior exposure to murine or humanized antibodies.

          -  Prior imaging studies with: I131 within the last month; In111 or Ga67 within the last
             2 weeks; Tc99m labelled RBCs, WBCs or albumin within the last 48 hours; Tc99m or F18
             within the last 24 hours; prior non-imaging, non-therapeutic nuclear medicine studies
             with I131 (eg., 24-hour RAI uptake) within the last 2 weeks.

          -  Previous participation in the present study.

          -  Geographic inaccessibility that precludes follow-up visits.

          -  Patient is unwilling or unable to provide informed consent.

          -  Patient is unsuitable for the study, at the Study Investigator's discretion.