Trousseau: Mortality Due to Malignancy in Patients With Idiopathic Venous Thromboembolism

Sponsor

Slotervaart Hospital (Other)

Overall Status

Terminated

CT.gov ID

NCT01088334

Collaborator

(none)

630

Enrollment

Locations

Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background

Patients with an idiopathic venous thromboembolism (IVTE) appear to have a risk of approximately 10% for symptomatic malignancy within 3 years after the IVTE. It is not clear if extensive screening for malignant disease leads to survival benefit in patients with an IVTE.

The SOMIT study learned that it is feasible to screen patients with an IVTE for malignancy and screening by means of a computer tomography (CT) of the chest and abdomen plus a mammography in women had the potential to be most cost-effective. The SOMIT study could not show a survival benefit due to the design of the study.

Primary objective: cancer related mortality

Methods:

The Trousseau study has been designed as a multicenter, prospective concurrently controlled cohort study.

Inclusion criteria:

Proven first symptomatic deep venous thromboembolic event;
Without: known risk factor for venous thromboembolism.

Exclusion criteria:

Proven deep venous thromboembolic event in the medical history, age under 40 years;
Patients without signs of malignancy after routine investigations (medical history, physical examination, laboratory investigations and chest X-ray) were included. Depending on the standard care in the hospital of interest, one group of patients has been screened by means of CT-chest and abdomen plus mammography, the other group had no additional investigations. Follow-up was aimed to be 3 years in both groups (at 3, 6, 12, 24 and 36 months after the thromboembolic event).

Data like mortality rate, morbidity due to screening procedures, additional investigations, number of cancer patients detected by the extensive screening, number of cancer patients three years after the IVTE, number and kind of investigations performed and information about cancer treatment and hospitalization was collected. If this information indicate a survival benefit these data enable us to perform a cost-effectiveness analysis.

Endpoint: Mortality.

Statistics:

Based on the prevalence of occult malignancy in VTE patients, the nature and stage of malignancies, the expected mortality, the anticipated detection of cancers and the early treatment related decrease in mortality we needed, in order to detect a true difference of this size with a 80 percent power and a two-tailed certainty of five percent, 750 patients for each group. Therefore, a total of 1500 patients is required for this study.

Condition or Disease	Intervention/Treatment	Phase
Venous Thromboembolism Malignancy	Other: screening

Detailed Description

Study design:

Although a randomized design is ideal for most studies we preferred a multicenter, prospective concurrently controlled cohort study design for our study. This is based on the experiences with the SOMIT study, in which two of the members of the executive committee (MH Prins, JMMB Otten) were involved.

The SOMIT study originally was supposed to have been conducted in eight countries. Medical ethical committees in most countries however considered it unethical to conduct this randomized study. Either because of the fact that the study contained a control arm, or because the screening arm (and thus the study itself) was considered to be unethical.

Patients as well as physicians found it difficult to let fate decide whether or not a patient would be screened for cancer, even though it was not clear if screening was life-saving. Moreover, during the SOMIT study, physicians noticed that patients with IVTE had their cancer detected early if they were in the screening group. This made it even more difficult to withhold additional screening procedures in patients in the routine group.

Many physicians themselves showed a strong preference for one of the arms of the study. Therefore they did not include as many patients as they could.

With a prospective cohort design we expect to avoid these problems. Per hospital that participates in the Trousseau study the physicians in that hospital will treat the patients according to the local preference for screening or no screening. All hospitals are matched regarding their population as much as possible.

Statistics:

The prevalence of occult cancer at the time of the thrombotic episode in patients with IVTE can be estimated to be 10%. Based on the nature and stage of malignancies, it is expected that half of these patients with occult malignant disease will die during the 3 years of follow-up, resulting in a cancer-related mortality of 5%. In addition, in approximately half of the patients with malignant disease who survived for 3 years, residual or recurrent cancer will be present. Therefore, cancer-related mortality or residual or recurrent cancer will be present in 75% of the patients with occult malignant disease at presentation, i.e., in 7-8% of the patients of the study cohort. We anticipate that approximately 80% of the occult malignancies will be detected by extensive screening and that early treatment will result in a 50% to 75% reduction of the 3-year incidence of cancer-related mortality or residual or recurrent malignancy.

Study Design

Study Type:

Observational

Actual Enrollment :

630 participants

Time Perspective:

Prospective

Official Title:

Trousseau Studie, Mortaliteit Door Maligniteit Bij patiënten Met Idiopatische Veneuze Tromboembolie

Study Start Date :

Dec 1, 2002

Actual Primary Completion Date :

May 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
IVTE, follow-up no malignancy at basal screening, no extensive screening
IVTE, screening No malignancy at basal screening, screening by means of CT-Chest/abdomen and mammography in women	Other: screening CT-Chest/abdomen and mammography in women

Arm

Intervention/Treatment

IVTE, follow-up

no malignancy at basal screening, no extensive screening

IVTE, screening

No malignancy at basal screening, screening by means of CT-Chest/abdomen and mammography in women

Other: screening

CT-Chest/abdomen and mammography in women

Outcome Measures

Primary Outcome Measures

Mortality [at 3, 6, 12, 24, 36 months after inclusion and at the end of study]
The responsible physician inform the investigators when a patient has died. The national registrar was checked at the end of the study for all patients

Secondary Outcome Measures

Residual objectified malignancy [at 3, 6, 12, 24, 36 months after inclusion]
The responsible physician documented all investigations performed. The malignancy have to be objectified. At the end of the study all living patients were contacted for medical status.
Recurrent objectified malignancy [at 3, 6, 12, 24, 36 after inclusion.]
The responsible physician documented all investigations performed. The malignancy have to be objectified. At the end of the study all living patients were contacted for medical status.
Malignancy detected by extensive screening, without alarm signs in routine examinations [at 3 months after inclusion]
The responsible physician documented all investigations performed and documented in standardized manner the routine tests (medical history, physical examination, lab tests and Chest X-ray. The malignancy have to be objectified inconnection with and due to screening tests and eventually further investigations.
Costs of screening, of additional tests after screening [at end of study.]
All costs of routine tests (consult of phycisians, lab tests, X-Chest) are known and documented, as are the costs of the screening tests and, if performed the costs of further evaluation in case of additional tests, admitions etc..
Medical complications of screening tests [at 3 + 6 months and end of study]
The screening tests had no risk of damage other than radiation. The results of these tests however could urge for invasive tests that could potentially harm patients. Therefore the harm done by screening tests or the resulting tests were documented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Proven first symptomatic deep venous thromboembolic event;
No known malignancy
Without: trauma of the legs, surgery within the last 2 months, immobilization within the last 2 months, thrombocytosis (> 1000 x 109), clinical severe dehydration, deficiency of anti-thrombin III, protein C/S, Factor V Leiden mutation , Prothrombine mutation or circulating lupus anticoagulants, pregnancy or post-partum period
No indication for malignancy at routine investigations(medical history, physical examination, routine blood tests and chest X-ray)

Exclusion Criteria:

Proven deep venous thromboembolic event in the medical history
age under 40 years;

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Meander Medisch Centrum	Amersfoort	Netherlands	3818 ES
2	Slotervaarthospital	Amsterdam	Netherlands	1066 EC
3	Onze Lieve Vrouwe Gasthuis	Amsterdam	Netherlands	1090 HM
4	Academic Medical Center	Amsterdam	Netherlands	1101 AZ
5	Maxima Medisch Centrum	Eindhoven	Netherlands	5631 BM
6	Academisch Ziekenhuis Groningen	Groningen	Netherlands	9713 GZ
7	Westfries Gasthuis	Hoorn	Netherlands	1624 NP
8	Academisch Ziekenhuis Maastricht	Maastricht	Netherlands	6229 HX
9	Diakonessenhuis Utrecht	Utrecht	Netherlands	3582 KE
10	Diakonessenhuis Zeist	Zeist	Netherlands	3707 HL

Sponsors and Collaborators

Slotervaart Hospital

Investigators

Principal Investigator: Hans-Martin MB Otten, MD PhD, Slotervaart hospital and Academic Medical Center
Study Director: Harry R Büller, Md PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Chair: Martin H Prins, MD PhD, Maastricht Universitair Medisch Centrum
Study Chair: Frederiek F v. Doormaal, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Chair: Wim Terpstra, MD PhD, Onze Lieve Vrouwe Gasthuis
Study Chair: René vd Griend, MD PhD, Diakonessenhuis, Utrecht
Study Chair: Marten Nijziel, MD PhD, Maxima Medical Center
Study Chair: Marcel A vd Ree, MD PhD, Diakonessenhuis Zeist
Study Chair: Jacob C Dutilh, MD, Meander Medisch Centrum
Study Chair: A t. Cate-Hoek, MD PhD, Maastricht Universitair Medisch Centrum
Study Chair: Simone M. vd Heiligenberg, MD, Dijklander Ziekenhuis
Study Chair: Jan vd Meer, MD PhD, University Medical Center Groningen