Clinical trial NCT00773448: Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism
Official title: Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism: an Open Randomized Controlled Trial Using a Comprehensive Abdomen/Pelvis Computed Tomography
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Venous Thromboembolism
Deep Vein Thrombosis
Pulmonary Embolism
Keywords: Cancer
Screening
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2008-10-16
Enrollment: 862
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: 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.


Eligibility criteria: 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:

    1. known active cancer;
    2. recent (less than 3 months) paralysis, paresis or plaster immobilization of the lower extremities;
    3. recently bedridden for period of 3 or more days, or major surgery, within the previous 12 weeks requiring general or regional anaesthesia;
    4. previous unprovoked VTE;
    5. 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:

    1. patients with a high/intermediate pre-test probability (Wells' model \> 4) + high probability V/Q scan;
    2. positive pulmonary angiogram; or
    3. 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

Primary outcomes:
measure: 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.
timeFrame: 1 year
Secondary outcomes:
measure: Overall mortality
timeFrame: 1 year
measure: Recurrent VTE
timeFrame: 1 year
measure: Early malignancy: T1-2N0M0 as per the World Health Organization TNM classification system
timeFrame: 1 year
measure: QALYs gained
timeFrame: 1 year
measure: Incremental cost-effectiveness ratio
timeFrame: 1 year
measure: Adverse events with cCT
timeFrame: 1 year
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Capital Health Centre for Research
state: Nova Scotia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Sacre-Coeur Hospital
state: Quebec
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: St. Mary's Hospital Center
state: Quebec
Study officials:
affiliation: The Ottawa Hospital Research Institute
name: Marc Carrier, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carrier M, Le Gal G, Wells PS, Fergusson D, Ramsay T, Rodger MA. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med. 2008 Sep 2;149(5):323-33. doi: 10.7326/0003-4819-149-5-200809020-00007.
citation: Carrier M, Lazo-Langner A, Shivakumar S, Tagalakis V, Zarychanski R, Solymoss S, Routhier N, Douketis J, Danovitch K, Lee AY, Le Gal G, Wells PS, Corsi DJ, Ramsay T, Coyle D, Chagnon I, Kassam Z, Tao H, Rodger MA; SOME Investigators. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med. 2015 Aug 20;373(8):697-704. doi: 10.1056/NEJMoa1506623. Epub 2015 Jun 22.
citation: Robertson L, Broderick C, Yeoh SE, Stansby G. Effect of testing for cancer on cancer- or venous thromboembolism (VTE)-related mortality and morbidity in people with unprovoked VTE. Cochrane Database Syst Rev. 2021 Oct 1;10(10):CD010837. doi: 10.1002/14651858.CD010837.pub5.
citation: Ihaddadene R, Corsi DJ, Lazo-Langner A, Shivakumar S, Zarychanski R, Tagalakis V, Solymoss S, Routhier N, Douketis J, Le Gal G, Carrier M. Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism. Blood. 2016 Apr 21;127(16):2035-7. doi: 10.1182/blood-2015-11-682963. Epub 2016 Jan 27.