Mortality Due to Malignancy in Patients With Idiopathic Venous Thromboembolism (Trousseau)

This study has been terminated.
(Terminated because of futility to continue, after planned interim analysis.)
Sponsor:
Information provided by:
Slotervaart Hospital
ClinicalTrials.gov Identifier:
NCT01088334
First received: February 25, 2010
Last updated: March 26, 2010
Last verified: March 2010
  Purpose

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:

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

Exclusion criteria:

  1. Proven deep venous thromboembolic event in the medical history, age under 40 years;
  2. 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 Intervention
Venous Thromboembolism
Malignancy
Other: screening

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Trousseau Studie, Mortaliteit Door Maligniteit Bij patiënten Met Idiopatische Veneuze Tromboembolie

Resource links provided by NLM:


Further study details as provided by Slotervaart Hospital:

Primary Outcome Measures:
  • Mortality [ Time Frame: at 3, 6, 12, 24, 36 months after inclusion and at the end of study ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: at 3, 6, 12, 24, 36 months after inclusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 3, 6, 12, 24, 36 after inclusion. ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 3 months after inclusion ] [ Designated as safety issue: No ]
    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 [ Time Frame: at end of study. ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 3 + 6 months and end of study ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 630
Study Start Date: December 2002
Study Completion Date: December 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Consecutive patients with IVTE diagnosed in academical centres and teaching hospitals in the Netherlands

Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088334

Locations
Netherlands
Meander Medisch Centrum
Amersfoort, Netherlands, 3818 ES
Academic Medical Center
Amsterdam, Netherlands, 1101 AZ
Slotervaarthospital
Amsterdam, Netherlands, 1066 EC
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1090 HM
Maxima Medisch Centrum
Eindhoven, Netherlands, 5631 BM
Academisch Ziekenhuis Groningen
Groningen, Netherlands, 9713 GZ
Westfries Gasthuis
Hoorn, Netherlands, 1624 NP
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6229 HX
Diakonessenhuis Utrecht
Utrecht, Netherlands, 3582 KE
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 Westfriesgasthuis
Study Chair: Jan vd Meer, MD PhD Universitair Medisch Centrum Groningen
  More Information

Publications:

Responsible Party: Dr. JMMB Otten, pi, Slotervaart hospital
ClinicalTrials.gov Identifier: NCT01088334     History of Changes
Other Study ID Numbers: Trousseau studie
Study First Received: February 25, 2010
Last Updated: March 26, 2010
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Slotervaart Hospital:
Idiopathic venous thromboembolism
Malignancy
screening

Additional relevant MeSH terms:
Neoplasms
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Thrombosis
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014