Comparison of Accidents and Their Circumstances With Oral Anticoagulants

Embolism and Thrombosis Clinical Trial

— CACAO  

Official title:

Comparison of Accidents and Their Circumstances With Oral Anticoagulants. The CACAO Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02376777
• Other study ID #: DCIC 15 09
• Status: Completed
• Phase: N/A
• First received: February 26, 2015
• Last updated: June 27, 2017
• Start date: April 2014
• Est. completion date: June 2017

Study information

• Verified date: June 2017
• Source: CNGE IRMG Association
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Differences in efficacy and safety between new oral anticoagulants (NOAC) and vitamin K antagonist (VKA) in real practice remain uncertain.

The few existing ambulatory studies did not answer all NOAC specific issues, such as prescription habits and motives, patients characteristics, biological monitoring, as well as the occurrence of major and minor thromboembolic events, especially in France where warfarin is less frequently prescribed.

Therefore, in order to describe clinical and follow up characteristics of patients receiving oral anticoagulants, the investigators will set up a national prospective cohort to compare the occurrence of thromboembolic events between VKA and NOAC in primary care.

Description:

The method includes the use of a national prospective observational cohort, involving 444 general practitioners From april to december 2014, health data of any adult patient consulting a general practitioner and receiving an oral anticoagulant treatment has been entered in a database. Each patient received an information for agreement to participate to the study (agreement for stastical analysis of their health data during one year follow up).

In March 2015, half of those patients will be chosen (stratification), using a matched stratification process, and will be followed up over one year. Every three months, data regarding the occurrence of therapeutics changes, episodes of excessive bleeding, and thromboembolic events will be collected by general practitioners.

The data will be analysed by: - describing the characteristics of patients receiving oral anticoagulant treatment; - describing the changes of medications over the year ; - comparing the occurrence of episodes of excessive bleeding ; - comparing the occurrence of thromboembolic events in patients using VKA versus patients using NOAC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4162
• Est. completion date: June 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria :

• Patient consulting a GP

• Patient Whatever the reason for consultation

• Aged >18 years

• Receiving oral anticoagulant treatment by NOAC (apixaban, dabigatran or rivaroxaban) or VKA (acenocoumarol, fluindione, or warfarin)

• Whatever the indication (prevention or treatment).

• Having the following indications for anticoagulant treatment : non-valvular atrial fibrillation, prevention of DVT / PE (excluding orthopedic post-surgery) treatment DVT / PE

Exclusion Criteria :

• Aged <18 years

• Receiving concomitant injectable anticoagulant treatment (including relay phase)

• Follow up impossible.

Related Conditions & MeSH terms

• Cardiovascular Complications
• Embolism
• Embolism and Thrombosis
• Hemorrhagic Disorders
• Thrombosis

Intervention

Other:
• Follow up
each three months during one year of follow up, general practioners will entered health data in database (hemorrhagic events, changes of medication, biological data...)

Locations

Country	Name	City	State
France	Office-based practitioner	Albens
France	Office-based practitioner	Bordeaux
France	Office-based practitioner	Chablis
France	Office-based general practitioner	Dessenheim
France	Office-based general practitioner	Dijon
France	Office-based practitioner	Flumet
France	Office-based practitioner	Gemenos
France	Office-based general practitioner	Grenay
France	Office-based general practitioner	Guesnain
France	Office-based general practitioner	Hatten
France	Office-based practitioner	Hinx
France	Office-based practitioner	La Madeleine
France	Office-based practitioner	Les Marches
France	Office-based practitioner	Limoges
France	Office-based practitioner	Mulsanne
France	Office-based practitioner	Outreau
France	Office-based general practitioner	Paris
France	Office-based general practitioner	Rupt-sur-moselle
France	Office-based practitioner	Saint Jean D'arvey
France	Office-based general practitioner	Saint-amant-tallende
France	Office-based practitioner	Saint-etienne
France	Office-based practitioner	Saint-jean-de-braye
France	Office-based practitioner	Saultain
France	Office-based general practitioner	Sellieres
France	Office-based practitioner	Seraincourt
France	Office-based general practitioner	Soisy-sous-montmorency
France	Office-based practitioner	St Georges D'orques
France	Office-based general practioner	Strasbourg
France	Office-based practitioner	Tournus
France	Office-based general practitioner	Tours
France	Office-based practitioner	Villeurbanne
France	Office-based practitioner	Vitry-sur-seine
France	Office-based general practitioner	Vourey

Sponsors (3)

Lead Sponsor	Collaborator
CNGE IRMG Association	Floralis, University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (11)

Adam SS, McDuffie JR, Ortel TL, Williams JW Jr. Comparative effectiveness of warfarin and new oral anticoagulants for the management of atrial fibrillation and venous thromboembolism: a systematic review. Ann Intern Med. 2012 Dec 4;157(11):796-807. Review. — View Citation

Douketis J, Tosetto A, Marcucci M, Baglin T, Cosmi B, Cushman M, Kyrle P, Poli D, Tait RC, Iorio A. Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis. BMJ. 2011 Feb 24;342:d813. doi: 10.1136/bmj.d813. Review. — View Citation

Galanaud JP, Sevestre-Pietri MA, Bosson JL, Laroche JP, Righini M, Brisot D, Boge G, van Kien AK, Gattolliat O, Bettarel-Binon C, Gris JC, Genty C, Quere I; OPTIMEV-SFMV Investigators. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost. 2009 Sep;102(3):493-500. doi: 10.1160/TH09-01-0053. — View Citation

Kearon C. Natural history of venous thromboembolism. Circulation. 2003 Jun 17;107(23 Suppl 1):I22-30. Review. — View Citation

Larsen TB, Rasmussen LH, Skjøth F, Due KM, Callréus T, Rosenzweig M, Lip GY. Efficacy and safety of dabigatran etexilate and warfarin in "real-world" patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol. 2013 Jun 4;61(22):2264-73. doi: 10.1016/j.jacc.2013.03.020. Epub 2013 Apr 3. — View Citation

Mantilla CB, Horlocker TT, Schroeder DR, Berry DJ, Brown DL. Frequency of myocardial infarction, pulmonary embolism, deep venous thrombosis, and death following primary hip or knee arthroplasty. Anesthesiology. 2002 May;96(5):1140-6. Erratum in: Anesthesiology 2002 Aug;97(2):531. — View Citation

Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol. 2012 Aug 1;110(3):453-60. doi: 10.1016/j.amjcard.2012.03.049. Epub 2012 Apr 24. Review. — View Citation

Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014 Mar 15;383(9921):955-62. doi: 10.1016/S0140-6736(13)62343-0. Epub 2013 Dec 4. — View Citation

Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. — View Citation

Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012 Mar 12;172(5):397-402. doi: 10.1001/archinternmed.2011.1666. Epub 2012 Jan 9. Review. — View Citation

You JJ, Singer DE, Howard PA, Lane DA, Eckman MH, Fang MC, Hylek EM, Schulman S, Go AS, Hughes M, Spencer FA, Manning WJ, Halperin JL, Lip GYH. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e531S-e575S. doi: 10.1378/chest.11-2304. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical characteristics	The profile of patients receiving VKA or NOAC will be described by the following variables: Molecule, duration, dosage; Indication: Atrial fibrillaton valvular or not / DVT / PE / Other, Prevention / Treatment; Age, sex, weight, height; Medication adherence ( as perceived by the GP ); Renal function; CHA2DS2-VASc Score; HAS-BLED Score; RIETE score; unstable INR; Comorbidities: anemia, diabetes, kidney disease, liver disease, hypertension, heart failure, stroke, peripheral vascular desease, myocardial infarction (MI).; Concomitant treatments: NSAIDs, antiplatelets, other treatments with potentials interactions	at baseline
Secondary	Bleeding events	Compare annual impact of bleeding events between patients receiving NOAC and VKA. Bleeding will be collected according to the International Society on Thrombosis and Haemostasis (ISTH) and BARC classification	at baseline, 3, 6, 9 and 12 months
Secondary	Thrombotic events	Compare annual impact of thrombotic events (Ischemic stroke, DVT, PE, acute coronary syndrome) between patients receiving NOAC and VKA on further indications : non-valvular ACFA (excluding mitral regurgitation grade 3 and 4), preventing DVT / PE , DVT/ EP treatment	at baseline, 3, 6, 9 and 12 months
Secondary	Death	Describe the causes of death (including EP or cardiac events)	at baseline, 3, 6, 9 and 12 months
Secondary	Therapeutic classes	Describe the changes of therapeutic classes and reasons in NOAC and VKA treated population. Changes in indication for medicines, changes in mode and type of anticoagulant therapy	at baseline, 3, 6, 9 and 12 months
Secondary	Bleeding score	Assess the relevance of different scores to predict the risk of bleeding. Comparison of the diagnostic performance of different classical scores by studying the corresponding AUC ROC curves	at baseline, 3, 6, 9 and 12 months