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: i) patients with suspected first DVT who have a moderate or high pre-test probability (PTP) for DVT and a normal CUS; ii) patients with suspected recurrent DVT; and iii) 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 a 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 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: i) identify small non-occlusive proximal DVT or distal DVT in patients with a moderate or high PTP and normal CUS; ii) differentiate old from new DVT in patients with suspected recurrent DVT; iii) diagnose or exclude DVT in patients in whom CUS is not technically feasible; and iv) 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 (a) ThromboView® was well tolerated, with no significant toxicity in studies involving animals and healthy volunteers, and (b) it has shown promise in Phase I trials as a non-invasive diagnostic test for acute DVT.

Condition	Intervention	Phase
Deep Vein Thrombosis	Drug: ThromboView	Phase II

Further Study Details: 

Primary Outcomes: To provide estimates of the sensitivity of [99mTc] ThromboView® in patients with confirmed initial DVT,; To provide estimates of the specificity of [99mTc] ThromboView® in patients with excluded initial DVT.
Secondary Outcomes: 1)To provide estimates of the sensitivity of [99mTc] ThromboView® in patients with confirmed recurrent DVT, and estimates of the specificity of [99mTc] ThromboView® in patients with suspected recurrent DVT in whom disease recurrence has been excluded.; 2) To provide estimates of the sensitivity and specificity of [99mTc] ThromboView® for DVT at the 1-hour and 3-hour imaging time points.; 3) To provide estimates of the sensitivity and specificity of [99mTc] ThromboView® for imaging proximal DVT and distal DVT.
Expected Total Enrollment:  180

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1) Adult man or woman, aged ≥18 years, presenting with suspected lower-limb initial or recurrent DVT.

2) Moderate or high pre-test probability (PTP) for DVT.

3) Onset of symptoms occurred within the last 7 days.

4) 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:

1) Receiving anticoagulant therapy at therapeutic doses for >3 days.

2) Life expectancy <3 months.

3) Patient with a renal transplant.

4) Renal dysfunction: serum creatinine >1.5x upper limit of normal range.

5) Hepatic dysfunction: serum transaminases >3x upper limit of normal range.

6) Current pregnancy or lactation, or conception intended within 90 days of enrolment

7) Of childbearing potential and is unwilling to use adequate contraception for 30 days following enrolment

8) Unable to undergo lower limb ascending venography on symptomatic leg(s).

9) Allergy or other contraindication to intravenous contrast dye.

10) Prior exposure to murine or humanized antibodies.

11) 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.

12) Previous participation in the present study.

13) Geographic inaccessibility that precludes follow-up visits.

14) Patient is unwilling or unable to provide informed consent.

15) Patient is unsuitable for the study at the Study Investigator’s discretion.

Please refer to this study by ClinicalTrials.gov identifier  NCT00123734

Susan Haley      905 527 2299  Ext. 42615    haleys@mcmaster.ca
Lorna Homes      905 527 2299  Ext. 43799    lhomes@mcmaster.ca

California
      UCSD Medical Centre, San Diego,  California,  82103-9378,  United States; Recruiting
      UC Davis, Sacramento,  California,  95817,  United States; Recruiting
Michigan
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States; Recruiting
Ohio
      Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States; Recruiting
Oklahoma
      University of Oklahoma, Health Sciences Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Canada, Ontario
      McMaster University, Hamilton Health Sciences, Hamilton,  Ontario,  L8N 3Z5,  Canada; Recruiting
      Henderson General Site, Hamilton,  Ontario,  L8V1C3,  Canada; Recruiting
      Hamilton General Hospital, Hamilton,  Ontario,  L8L 2X2,  Canada; Recruiting
      St. Joseph''''s Healthcare, Hamilton,  Ontario,  L8N4A6,  Canada; Recruiting
Canada, Quebec
      Hotel-Dieu Du CHUM, Montreal,  Quebec,  H2W1T8,  Canada; Recruiting
      Hopital Maisonneuve-Rosemont, Montreal,  Quebec,  H1T 2M4,  Canada; Recruiting
      Centre hospitalier de L''''Universite Laval, Sainte-Foy,  Quebec,  G1V 4G2,  Canada; Not yet recruiting

Study chairs or principal investigators

Jim Douketis, MD FRCPC,  Principal Investigator,  Hamilton Health Sciences   
Jeff Ginsberg, MD FRCPC,  Principal Investigator,  Hamilton Health Sciences   

Study ID Numbers:  CAN/US-001-II-DVT
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 25, 2005
ClinicalTrials.gov Identifier:  NCT00123734
Health Authority: United States: Food and Drug Administration; Canada: Health Canada
ClinicalTrials.gov processed this record on 2005-07-26