Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism

Study Overview
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Brief Summary
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Blood clots in leg veins (deep vein thrombosis) or lung arteries (pulmonary embolism) that happen for no reason (i.e. unexplained) are both called unprovoked venous thromboembolism (VTE). These unexplained blood clots can be the first symptom of cancer. Up to 10% of patients with unexplained blood clots will be diagnosed with cancer within one year of their blood clot diagnosis. These cancers can be found anywhere in the body although the relationship appears stronger with the pancreas, ovary and liver. Cancer testing in patients with blood clots is controversial. There is presently a wide variety of expert opinions and practices. Previous studies showed that a limited cancer screen including a medical history, physical examination, basic blood work and chest X-ray, will find about 90% of cancers. More recent and better designed studies showed that the limited cancer screen misses many cancers and needs to be improved. More extensive cancer testing may find more cancers but is potentially uncomfortable for patients, costs a lot of money and involves a lot of people. The comprehensive computed tomography is less uncomfortable, inexpensive, radiological test made to find many cancers at once. Thus, the scientific question to be asked is: Does a comprehensive computed tomography miss less cancers than a limited cancer screen in patients with blood clots? The main goal of this study is to find out if a comprehensive computed tomography misses less cancers than a limited cancer screen in patients with unexplained blood clots. The second goal of the study is 1) to find out if a comprehensive computed tomography finds more curable cancers than the limited cancer screen; 2) to find out if the patients diagnosed with cancer are still alive and cancer-free after one year (i.e. the patients with curable cancer were treated and are doing well); 3) to prove that a negative comprehensive computed tomography means that the patient will not have cancer and; 4) to find out if a comprehensive computed tomography is well tolerated and safe for patients.

Official Title
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Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism: an Open Randomized Controlled Trial Using a Comprehensive Abdomen/Pelvis Computed Tomography

Conditions
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Venous Thromboembolism, Deep Vein Thrombosis, Pulmonary Embolism

Intervention / Treatment
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* Device: Comprehensive computed tomography of the abdomen/pelvis
* Other: Limited Malignancy Screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a new diagnosis of unprovoked proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) will be eligible to participate into the study: Unprovoked VTE is defined as the absence of any of the following predisposing factors: known active cancer; recent (less than 3 months) paralysis, paresis or plaster immobilization of the lower extremities; recently bedridden for period of 3 or more days, or major surgery, within the previous 12 weeks requiring general or regional anaesthesia; previous unprovoked VTE; known thrombophilia (hereditary or acquired) Proximal DVT is defined as a non-compressibility of any vein segment from the common femoral vein to the trifurcation of the popliteal vein or a persistent intra-luminal filling defect of the iliac, common femoral, superficial femoral or popliteal veins on contrast venography. Pulmonary embolism is defined as: patients with a high/intermediate pre-test probability (Wells' model > 4) + high probability V/Q scan; positive pulmonary angiogram; or spiral CT demonstrating intraluminal filling defect in a vessel larger than a segmental artery Exclusion Criteria: Patients will be excluded from the study if they have any of the following criteria: Age < 18 years-old; Refusal or inability to provide informed consent; Greater than 21 days post diagnosis of idiopathic VTE Index VTE event of UEDVT or unusual site DVT Diagnosis of SSPE in the absence of above or below knee DVT Allergy to contrast media; Creatinine clearance < 60 ml/min; Claustrophobia or agoraphobia; Weight > 130 kg; Diagnosis of ulcerative colitis; and Diagnosis of glaucoma Current pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Limited Malignancy Screening<br> | Other: Limited Malignancy Screening<br>* 1) A complete medical history and physical examination; 2) complete blood count; 3) liver function tests (AST, ALT, ALP, bilirubin, LDH); 4) renal function test (creatinine); 5) chest X-ray (if not performed in the past year) In women, a pap smear/pelvic examination (if > 18 and < 70 years old and not performed during the past year),a mammogram (> 50 years old) will be performed if not conducted in last year. Similarly for men, prostate examination +/- PSA testing (>40 years old) will be performed if not conducted in the past year.<br>|
| Experimental: Extensive Malignancy Screening<br>Limited screen as described above in combination with comprehensive computed tomography of the abdomen/pelvis | Device: Comprehensive computed tomography of the abdomen/pelvis<br>* Virtual colonoscopy and gastroscopy, a biphasic enhanced CT for hepatoma and renal cell carcinoma, parenchymal pancreatogram with minimum intensity projection (MinIP) reformation for pancreatic carcinoma, and finally uniphasic enhanced CT of distended bladder for bladder and ovarian carcinomas.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Previously undiagnosed malignancy missed by malignancy screening defined as biopsy proven tissue diagnosis of malignancy diagnosed from the time of malignancy screening completion to the end of the 1 year follow-up period. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall mortality |  | 1 year | 
| Recurrent VTE |  | 1 year | 
| Early malignancy: T1-2N0M0 as per the World Health Organization TNM classification system |  | 1 year | 
| QALYs gained |  | 1 year | 
| Incremental cost-effectiveness ratio |  | 1 year | 
| Adverse events with cCT |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Screening