Screening for Previously Undiagnosed Malignancy in Patients With Unprovoked Venous Thromboembolism - Full Text View

Sponsored by:	Ottawa Health Research Institute
Information provided by:	Ottawa Health Research Institute
ClinicalTrials.gov Identifier:	NCT00773448

Purpose

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" misses 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 two years (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.

Condition	Intervention
Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism	Device: Comprehensive computed tomography of the abdomen/pelvis Other: Limited Malignancy Screening

MedlinePlus related topics: CT Scans Cancer Deep Vein Thrombosis Pulmonary Embolism

Drug Information available for: Calcium gluconate Creatinine X-Rays

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Screening, Randomized, Open Label, Parallel Assignment, Efficacy Study
Official Title:	Screening for Previously Undiagnosed Malignancy in Patients With Unprovoked Venous Thromboembolism: a Randomized Controlled Trial Using a Comprehensive Computed Tomography of the Abdomen/Pelvis

Further study details as provided by Ottawa Health Research Institute:

Primary Outcome Measures:

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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall mortality [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Recurrent VTE [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Early malignancy: T1-2N0M0 as per the World Health Organization TNM classification system [ Time Frame: 1 year ] [ Designated as safety issue: No ]
QALYs gained [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Incremental cost-effectiveness ratio [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Adverse events with cCT [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	862
Study Start Date:	September 2008
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Limited Malignancy Screening: Active Comparator	Other: Limited Malignancy Screening 1) A complete medical history and physical examination; 2) complete blood count; 3) serum electrolytes (including calcium); 3) liver function tests (AST, ALT, ALP, bilirubin, LDH); 4) renal function test (creatinine); 5) chest X-ray; and 6) urinalysis. In women, a breast examination, pap smear/pelvic examination (if > 18 and < 70 years old) and mammogram (> 50 years old) will be performed if not conducted in last year. Similarly, prostate examination +/- PSA testing (>40 years old) will be performed if not conducted in the last years.
Extensive Malignancy Screening: Experimental Limited screen as described above in combination with comprehensive computed tomography of the abdomen/pelvis	Device: Comprehensive computed tomography of the abdomen/pelvis 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.

Arms

Assigned Interventions

Limited Malignancy Screening: Active Comparator

Other: Limited Malignancy Screening

1) A complete medical history and physical examination; 2) complete blood count; 3) serum electrolytes (including calcium); 3) liver function tests (AST, ALT, ALP, bilirubin, LDH); 4) renal function test (creatinine); 5) chest X-ray; and 6) urinalysis.

In women, a breast examination, pap smear/pelvic examination (if > 18 and < 70 years old) and mammogram (> 50 years old) will be performed if not conducted in last year. Similarly, prostate examination +/- PSA testing (>40 years old) will be performed if not conducted in the last years.

Extensive Malignancy Screening: Experimental

Limited screen as described above in combination with comprehensive computed tomography of the abdomen/pelvis

Device: Comprehensive computed tomography of the abdomen/pelvis

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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); or
  6. Current pregnancy
- 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;
Allergy to contrast media;
Creatinine clearance < 60 ml/min;
Claustrophobia or agoraphobia;
Weight > 130 kg;
Diagnosis of ulcerative colitis; and
Diagnosis of glaucoma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773448

Contacts

Contact: Marc Carrier, MD MSc	613-737-8899 ext 79842	mcarrier@ottawahospital.on.ca
Contact: Melissa Spero, RN	613-737-8899 ext 12691	mspero@ohri.ca

Locations

Canada, Ontario
Ottawa Hospital	Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Melissa Spero, RN 613-737-8899 ext 12691 mspero@ohri.ca
Principal Investigator: Marc Carrier, MD MSc
Sub-Investigator: Marc A Rodger, MD MSc
Sub-Investigator: Philip S Wells, MD MSc
Sub-Investigator: Tim Ramsay, PhD

Sponsors and Collaborators

Ottawa Health Research Institute

More Information

Publications:

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. Review.

Responsible Party:	Ottawa Health Research Institute ( Marc Carrier MD MSc FRCPC, Associate Scientist )
Study ID Numbers:	2004723-01H
Study First Received:	October 14, 2008
Last Updated:	October 15, 2008
ClinicalTrials.gov Identifier:	NCT00773448
Health Authority:	Canada: Ethics Review Committee

Keywords provided by Ottawa Health Research Institute:

Cancer
Screening

Study placed in the following topic categories:

Calcium, Dietary
Embolism and Thrombosis
Pulmonary Embolism
Respiratory Tract Diseases
Embolism
Lung Diseases

Vascular Diseases
Bilirubin
Venous Thrombosis
Venous Thromboembolism
Thromboembolism
Thrombosis

Additional relevant MeSH terms:

Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 14, 2009