Anti Xa Activity in Cancer Patients Receiving Low-molecular-weight Heparin for Venous Thromboembolism

NCT02898051 | Unknown

• 3 other identifiers: P100127PHRC10_02-542011-000154-36
• Study Type: observational
• Target: 370
• Locations: 1 country
• Sites: 8

Brief Summary

Low molecular weight heparins (LMWH) are the reference molecule for the long term treatment of venous thromboembolism (VTE) in cancer patients but remains, however, associated with a high risk of recurrent thromboembolism. The high rate of recurrence may result from alterations in the pharmacokinetics of LMWH. The primary purpose of the study is to compare the pharmacokinetics of anti-Xa activity in patients with cancer and patients without cancer treated with curative dose of low molecular weight heparins (LMWH) for venous thromboembolism (VTE). The secondary purposes are 1/ to study the correlation between anti-Xa LMWH and concentration of plasma heparanase and 2/ to evaluate the predictive nature of the anti-Xa activity on the occurrence of thromboembolic recurrence in cancer patients treated with LMWH for VTE.

Conditions

Neoplasms; Venous Thromboembolism

Keywords

heparin low-molecular-weight;pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• anti-Xa activity

  The measurement of anti-Xa activity will be performed four times during the initial treatment for each patient (or during the first 5 to 10 days of treatment) and will establish pharmacokinetic modeling (population type approach, nonlinear model mixed-effect) of the low molecular weight heparin therapy in subjects with cancer or not. In order to obtain a curve of relevant anti-Xa activity.

  10 days

Secondary Outcomes (3)

• hemorrhage

  6 months

• all cause mortality

  6 months

• thromboembolic recurrences

  6 months

Study Arms (2)

Venous Thromboembolism and cancer

Patients hospitalized for Venous Thromboembolism and having a cancer. Inclusion (as soon as the diagnosis of venous thromboembolism is confirmed). One tube of blood taken before the start of treatment (at the time of another blood sample) for determination of heparanase. After the start of treatment: three tubes of blood drawn for determination of anti-Xa activity. Assays will be centrally performed, blinded from the clinical data and from the group knowledge of the group patient.

Venous Thromboembolism and non cancer

Patients hospitalized for Venous Thromboembolism and not having a cancer. Inclusion (as soon as the diagnosis of venous thromboembolism is confirmed). One tube of blood taken before the start of treatment (at the time of another blood sample) for determination of heparanase. After the start of treatment: 3 tubes of blood drawn for determination of anti-Xa activity. Assays will be centrally performed, blinded from the clinical data and from the group knowledge of the group patient.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Hospitalized patients in tertiary care hospitals participating to the study and treated with curative dose of low molecular weight heparins (LMWH) for venous thromboembolism (VTE).

You may qualify if:

• Case:
• Being affiliated to a social security scheme
• Having an active solid or hematological cancer (myeloma or lymphoma), histologically or cytologically confirmed, for which the active state will be defined by the existence of a tumoral active disease or an incomplete tumoral resection or the persistence of high tumor markers after complete resection of the tumor.
• The venous thromboembolism disease has to be:
• A deep vein thrombosis of lower extremity (proximal or distal) confirmed by the lack of compressibility of a venous segment under the ultrasound probe or the presence of a venous gap in CT venography or phlebography;
• or a thrombosis of the vena cava or the iliac vein confirmed by an abdominal CT scan with contrast or a venous ultrasound or an ilio-cavography;
• or a pulmonary embolism confirmed according to the guidelines of the European Society of Cardiology : through a gap in a pulmonary artery, at least segmental or multiple gaps sub-segmental on spiral CT angiography of the pulmonary arteries or by a high appearance probability on a lung radionuclide imaging, or by clinical symptoms of pulmonary embolism accompanying symptomatic proximal vein thrombosis confirmed by a venous ultrasound or by an unexplained echocardiography acute pulmonary heart in presence of a high clinical probability and for patients who are unfit for transport and with cardiogenic shock
• The venous thromboembolism disease can be asymptomatic or incidentally discovered but is confirmed objectively.
• No cons-indication to low molecular weight heparin treatment at therapeutic dose.
• Prescription in the last 72 hours of a low molecular weight heparin treatment or fondaparinux at therapeutic dose.
• Control:
• Being affiliated to a social security scheme.
• Being afflicted with venous thromboembolism defined by the same criteria of cancer subjects.
• The venous thromboembolism disease can be asymptomatic or incidentally discovered but is confirmed objectively.
• No cons-indication to low molecular weight heparin treatment at therapeutic dose.

You may not qualify if:

• Case:
• Visceral vein thrombosis of the upper limb or venous thrombosis of the superior vena cava system because their scalability under treatment, including the risk of embolic recurrence is less known that pulmonary embolism and thrombosis of the lower limbs and their diagnostic modalities are less formalized.
• Tumor disease not confirmed histologically or cytologically.
• Follow-up after complete tumor resection without elevated tumor markers.
• Cons-indication to low molecular weight heparin treatment at therapeutic dose.
• Initial treatment with another anticoagulant molecule than LMWH or fondaparinux (thrombin inhibitor, direct factor Xa inhibitors)
• Severe renal impairment defined by a creatinine clearance below than 30 ml / min at baseline.
• Known pregnancy or lack of effective contraception for women of childbearing age or breastfeeding.
• Patient previously included in the study.
• Impossible follow-up.
• Life expectancy less than 6 months.
• Patient whose weight is greater than 100 Kg.
• Control:
• Not yet confirmed suspected malignant tumor pathology associated with the venous thromboembolism disease.
• Active cancer in the last 2 years.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Ministry of Health, France: collaborator
• National Cancer Institute, France: collaborator

Study Sites (8)

Hôpital d'instruction des armees Desgenettes

Lyon, Auvergne-Rhône-Alpes, 69003, France

Location

CHU de Saint-Etienne Hôpital Nord

Saint-Priest-en-Jarez, Auvergne-Rhône-Alpes, 42270, France

Location

CHU de Dijon

Dijon, Bourgogne-Franche-Comté, 21079, France

Location

Hôpital La Cavale Blanche

Brest, Brittany Region, 29609, France

Location

CHU Amiens - Hôpital Sud

Amiens, Picardie, 80054, France

Location

Hôpital Louis Mourier

Colombes, Île-de-France Region, 92700, France

Location

Hôpital Saint-Louis

Paris, Île-de-France Region, 75010, France

Location

Hôpital Europeen Georges Pompidou

Paris, Île-de-France Region, 75015, France

Location

Related Publications (5)

• Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006 Feb 27;166(4):458-64. doi: 10.1001/archinte.166.4.458.

  PMID: 16505267 BACKGROUND

• Khorana AA, Streiff MB, Farge D, Mandala M, Debourdeau P, Cajfinger F, Marty M, Falanga A, Lyman GH. Venous thromboembolism prophylaxis and treatment in cancer: a consensus statement of major guidelines panels and call to action. J Clin Oncol. 2009 Oct 10;27(29):4919-26. doi: 10.1200/JCO.2009.22.3214. Epub 2009 Aug 31.

  PMID: 19720907 BACKGROUND

• Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):454S-545S. doi: 10.1378/chest.08-0658.

  PMID: 18574272 BACKGROUND

• Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. doi: 10.1056/NEJMoa025313.

  PMID: 12853587 BACKGROUND

• Katz BZ, Muhl L, Zwang E, Ilan N, Herishanu Y, Deutsch V, Naparstek E, Vlodavsky I, Preissner KT. Heparanase modulates heparinoids anticoagulant activities via non-enzymatic mechanisms. Thromb Haemost. 2007 Dec;98(6):1193-9.

  PMID: 18064313 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biospecimen Description The total volume of blood collected for the study will be 44 mL for cancer patients and non cancer patients for the measurement of the following parameters: * anti-Xa activity; * heparanase; * platelet factor 4; * tissue factor; * tissue factor pathway inhibitor (TFPI); * P-selectin.

MeSH Terms

Conditions

Neoplasms; Venous Thromboembolism

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Guy Meyer, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 13, 2016
• Study Start: August 1, 2011
• Primary Completion: October 1, 2017
• Study Completion: January 1, 2018
• Last Updated: October 19, 2017

Record last verified: 2017-10

Locations

FR (8)