Mortality Due to Malignancy in Patients With Idiopathic Venous Thromboembolism (Trousseau)
Trousseau Studie, Mortaliteit Door Maligniteit Bij patiënten Met Idiopatische Veneuze Tromboembolie
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.
研究概览
详细说明
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.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Amersfoort、荷兰、3818 ES
- Meander Medisch Centrum
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Amsterdam、荷兰、1090 HM
- Onze Lieve Vrouwe Gasthuis
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Amsterdam、荷兰、1066 EC
- Slotervaarthospital
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Amsterdam、荷兰、1101 AZ
- Academic Medical Center
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Eindhoven、荷兰、5631 BM
- Maxima Medisch Centrum
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Groningen、荷兰、9713 GZ
- Academisch Ziekenhuis Groningen
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Hoorn、荷兰、1624 NP
- Westfries Gasthuis
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Maastricht、荷兰、6229 HX
- Academisch Ziekenhuis Maastricht
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Utrecht、荷兰、3582 KE
- Diakonessenhuis Utrecht
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Zeist、荷兰、3707 HL
- Diakonessenhuis Zeist
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-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
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;
学习计划
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
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IVTE, follow-up
no malignancy at basal screening, no extensive screening
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|
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IVTE, screening
No malignancy at basal screening, screening by means of CT-Chest/abdomen and mammography in women
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CT-Chest/abdomen and mammography in women
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Mortality
大体时间：at 3, 6, 12, 24, 36 months after inclusion and at the end of study
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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
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at 3, 6, 12, 24, 36 months after inclusion and at the end of study
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Residual objectified malignancy
大体时间：at 3, 6, 12, 24, 36 months after inclusion
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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.
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at 3, 6, 12, 24, 36 months after inclusion
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Recurrent objectified malignancy
大体时间：at 3, 6, 12, 24, 36 after inclusion.
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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.
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at 3, 6, 12, 24, 36 after inclusion.
|
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Malignancy detected by extensive screening, without alarm signs in routine examinations
大体时间：at 3 months after inclusion
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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.
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at 3 months after inclusion
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Costs of screening, of additional tests after screening
大体时间：at end of study.
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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..
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at end of study.
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Medical complications of screening tests
大体时间：at 3 + 6 months and end of study
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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.
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at 3 + 6 months and end of study
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合作者和调查者
调查人员
- 首席研究员：Hans-Martin MB Otten, MD PhD、Slotervaart hospital and Academic Medical Center
- 研究主任：Harry R Büller, Md PhD、Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- 学习椅：Martin H Prins, MD PhD、Maastricht Universitair Medisch Centrum
- 学习椅：Frederiek F v. Doormaal, MD PhD、Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- 学习椅：Wim Terpstra, MD PhD、Onze Lieve Vrouwe Gasthuis
- 学习椅：René vd Griend, MD PhD、Diakonessenhuis, Utrecht
- 学习椅：Marten Nijziel, MD PhD、Maxima Medical Center
- 学习椅：Marcel A vd Ree, MD PhD、Diakonessenhuis Zeist
- 学习椅：Jacob C Dutilh, MD、Meander Medisch Centrum
- 学习椅：A t. Cate-Hoek, MD PhD、Maastricht Universitair Medisch Centrum
- 学习椅：Simone M. vd Heiligenberg, MD、Dijklander ziekenhuis
- 学习椅：Jan vd Meer, MD PhD、University Medical Center Groningen
出版物和有用的链接
一般刊物
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- PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990 May 23-30;263(20):2753-9. doi: 10.1001/jama.1990.03440200057023.
- Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J Jr, Hobbins TE, et al. The clinical course of pulmonary embolism. N Engl J Med. 1992 May 7;326(19):1240-5. doi: 10.1056/NEJM199205073261902.
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- Goldberg RJ, Seneff M, Gore JM, Anderson FA Jr, Greene HL, Wheeler HB, Dalen JE. Occult malignant neoplasm in patients with deep venous thrombosis. Arch Intern Med. 1987 Feb;147(2):251-3.
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- Prins MH, Hettiarachchi RJ, Lensing AW, Hirsh J. Newly diagnosed malignancy in patients with venous thromboembolism. Search or wait and see? Thromb Haemost. 1997 Jul;78(1):121-5.
- O'Connor NT, Cederholm-Williams SA, Fletcher EW, Allington M, Sharp AA. Significance of idiopathic deep venous thrombosis. Postgrad Med J. 1984 Apr;60(702):275-7. doi: 10.1136/pgmj.60.702.275.
- Prandoni P, Lensing AW, Buller HR, Cogo A, Prins MH, Cattelan AM, Cuppini S, Noventa F, ten Cate JW. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med. 1992 Oct 15;327(16):1128-33. doi: 10.1056/NEJM199210153271604.
- Lensing AW, Prandoni P, Brandjes D, Huisman PM, Vigo M, Tomasella G, Krekt J, Wouter Ten Cate J, Huisman MV, Buller HR. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med. 1989 Feb 9;320(6):342-5. doi: 10.1056/NEJM198902093200602.
- Rance A, Emmerich J, Guedj C, Fiessinger JN. Occult cancer in patients with bilateral deep-vein thrombosis. Lancet. 1997 Nov 15;350(9089):1448-9. doi: 10.1016/S0140-6736(05)64210-9. No abstract available.
- Sannella NA, O'Connor DJ Jr. "Idiopathic" deep venous thrombosis: the value of routine abdominal and pelvic computed tomographic scanning. Ann Vasc Surg. 1991 May;5(3):218-22. doi: 10.1007/BF02329376.
- Cornuz J, Pearson SD, Creager MA, Cook EF, Goldman L. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med. 1996 Nov 15;125(10):785-93. doi: 10.7326/0003-4819-125-10-199611150-00001.
- Girolami A, Prandoni P, Zanon E, Bagatella P, Girolami B. Venous thromboses of upper limbs are more frequently associated with occult cancer as compared with those of lower limbs. Blood Coagul Fibrinolysis. 1999 Dec;10(8):455-7. doi: 10.1097/00001721-199912000-00001.
- Ahmed Z, Mohyuddin Z. Deep vein thrombosis as a predictor of cancer. Angiology. 1996 Mar;47(3):261-5. doi: 10.1177/000331979604700307.
- Subira M, Mateo J, Souto JC, Altes A, Fontcuberta J. Lack of association between venous thrombosis and subsequent malignancy in a retrospective cohort study in young patients. Am J Hematol. 1999 Mar;60(3):181-4. doi: 10.1002/(sici)1096-8652(199903)60:33.0.co;2-4.
- Biello DR, Mattar AG, McKnight RC, Siegel BA. Ventilation-perfusion studies in suspected pulmonary embolism. AJR Am J Roentgenol. 1979 Dec;133(6):1033-7. doi: 10.2214/ajr.133.6.1033.
- Dalen JE, Brooks HL, Johnson LW, Meister SG, Szucs MM Jr, Dexter L. Pulmonary angiography in acute pulmonary embolism: indications, techniques, and results in 367 patients. Am Heart J. 1971 Feb;81(2):175-85. doi: 10.1016/0002-8703(71)90128-1. No abstract available.
- Hull RD, Hirsh J, Carter CJ, Raskob GE, Gill GJ, Jay RM, Leclerc JR, David M, Coates G. Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism. Chest. 1985 Dec;88(6):819-28. doi: 10.1378/chest.88.6.819.
- Otten HM, Prins MH. A number needed to screen and cost-effectiveness analysis of the SOMIT-data. Haemostasis. 2001;31 Suppl 1:40-2. No abstract available.
- Piccioli A, Prandoni P. Screening for occult cancer in patients with idiopathic venous thromboembolism: yes. J Thromb Haemost. 2003 Nov;1(11):2271-2. doi: 10.1046/j.1538-7836.2003.00505.x. No abstract available.
- Lee AY. Screening for occult cancer in patients with idiopathic venous thromboembolism: no. J Thromb Haemost. 2003 Nov;1(11):2273-4. doi: 10.1046/j.1538-7836.2003.00490.x. No abstract available.
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- Piccioli A, Lensing AW, Prins MH, Falanga A, Scannapieco GL, Ieran M, Cigolini M, Ambrosio GB, Monreal M, Girolami A, Prandoni P; SOMIT Investigators Group. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J Thromb Haemost. 2004 Jun;2(6):884-9. doi: 10.1111/j.1538-7836.2004.00720.x.
- DI Nisio M, Otten HM, Piccioli A, Lensing AW, Prandoni P, Buller HR, Prins MH. Decision analysis for cancer screening in idiopathic venous thromboembolism. J Thromb Haemost. 2005 Nov;3(11):2391-6. doi: 10.1111/j.1538-7836.2005.01606.x.
- Nordstrom M, Lindblad B, Anderson H, Bergqvist D, Kjellstrom T. Deep venous thrombosis and occult malignancy: an epidemiological study. BMJ. 1994 Apr 2;308(6933):891-4. doi: 10.1136/bmj.308.6933.891.
- Sorensen HT, Mellemkjaer L, Steffensen FH, Olsen JH, Nielsen GL. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med. 1998 Apr 23;338(17):1169-73. doi: 10.1056/NEJM199804233381701.
- Baron JA, Gridley G, Weiderpass E, Nyren O, Linet M. Venous thromboembolism and cancer. Lancet. 1998 Apr 11;351(9109):1077-80. doi: 10.1016/S0140-6736(97)10018-6. Erratum In: Lancet 2000 Feb 26;355(9205):758.
- Beckers MM, Verzijlbergen JF, van Buul MM, Prins MH, Biesma DH. The potential role of positron emission tomography in the detection of occult cancer in 25 patients with venous thromboembolism. Ann Oncol. 2008 Jun;19(6):1203-4. doi: 10.1093/annonc/mdn156. Epub 2008 Apr 2. No abstract available.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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