Clinical trial NCT02376777: Comparison of Accidents and Their Circumstances With Oral Anticoagulants
Official title: Comparison of Accidents and Their Circumstances With Oral Anticoagulants. The CACAO Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiovascular Complications
Hemorrhagic Disorders
Embolism and Thrombosis
Keywords: Anticoagulants
Antithrombins
Atrial Fibrillation
Intracranial haemorrhage
Gastrointestinal haemorrhage
Myocardial infarction
Stroke
Venous thrombosis
Primary care
Lead sponsor: CNGE IRMG Association
Sponsor class: OTHER
Collaborators: name: Floralis
name: University Hospital, Grenoble
First posted: 2015-03-03
Enrollment: 4162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All adult patients with anticoagulant medication consulting their general practitioner will be included (N=7846), and after stratification, 4162 patients will be followed

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical characteristics
timeFrame: at baseline
Secondary outcomes:
measure: Bleeding events
timeFrame: at baseline, 3, 6, 9 and 12 months
measure: Thrombotic events
timeFrame: at baseline, 3, 6, 9 and 12 months
measure: Death
timeFrame: at baseline, 3, 6, 9 and 12 months
measure: Therapeutic classes
timeFrame: at baseline, 3, 6, 9 and 12 months
measure: Bleeding score
timeFrame: at baseline, 3, 6, 9 and 12 months
Other outcomes:
Locations:
city: Albens
country: France
facility: Office-based practitioner
city: Bordeaux
country: France
facility: Office-based practitioner
city: Chablis
country: France
facility: Office-based practitioner
city: Dessenheim
country: France
facility: Office-based general practitioner
city: Dijon
country: France
facility: Office-based general practitioner
city: Flumet
country: France
facility: Office-based practitioner
city: Gemenos
country: France
facility: Office-based practitioner
city: Grenay
country: France
facility: Office-based general practitioner
city: Guesnain
country: France
facility: Office-based general practitioner
city: Hatten
country: France
facility: Office-based general practitioner
city: Hinx
country: France
facility: Office-based practitioner
city: La Madeleine
country: France
facility: Office-based practitioner
city: Les Marches
country: France
facility: Office-based practitioner
city: Limoges
country: France
facility: Office-based practitioner
city: Mulsanne
country: France
facility: Office-based practitioner
city: Outreau
country: France
facility: Office-based practitioner
city: Paris
country: France
facility: Office-based general practitioner
city: Rupt-sur-moselle
country: France
facility: Office-based general practitioner
city: Saint Jean D'arvey
country: France
facility: Office-based practitioner
city: Saint-amant-tallende
country: France
facility: Office-based general practitioner
city: Saint-etienne
country: France
facility: Office-based practitioner
city: Saint-jean-de-braye
country: France
facility: Office-based practitioner
city: Saultain
country: France
facility: Office-based practitioner
city: Sellieres
country: France
facility: Office-based general practitioner
city: Seraincourt
country: France
facility: Office-based practitioner
city: Soisy-sous-montmorency
country: France
facility: Office-based general practitioner
city: St Georges D'orques
country: France
facility: Office-based practitioner
city: Strasbourg
country: France
facility: Office-based general practioner
city: Tournus
country: France
facility: Office-based practitioner
city: Tours
country: France
facility: Office-based general practitioner
city: Villeurbanne
country: France
facility: Office-based practitioner
city: Vitry-sur-seine
country: France
facility: Office-based practitioner
city: Vourey
country: France
facility: Office-based general practitioner
Study officials:
affiliation: IRMG
name: Joël COGNEAU, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Saint-Etienne
name: Paul FRAPPE, MD
role: STUDY_DIRECTOR
affiliation: University of Grenoble
name: Jean-Pierre JACQUET, MD
role: STUDY_DIRECTOR
affiliation: University of Grenoble
name: Jean-Luc BOSSON, MD PhD
role: STUDY_DIRECTOR
affiliation: IRMG
name: François Lacoin, MD
role: STUDY_DIRECTOR
References:
citation: Kearon C. Natural history of venous thromboembolism. Circulation. 2003 Jun 17;107(23 Suppl 1):I22-30. doi: 10.1161/01.CIR.0000078464.82671.78.
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.
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. doi: 10.1097/00000542-200205000-00017.
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.
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.
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.
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.
citation: 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. doi: 10.7326/0003-4819-157-10-201211200-00532.
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.
citation: Larsen TB, Rasmussen LH, Skjoth F, Due KM, Callreus 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.
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. doi: 10.1111/j.1538-7836.2005.01204.x.
citation: Frappe P, Cogneau J, Gaboreau Y, Abenhaim N, Bayen M, Guichard C, Jacquet JP, Lacoin F, Liebart S, Bertoletti L, Bosson JL; CACAO study investigators. Anticoagulants' Safety and Effectiveness in General Practice: A Nationwide Prospective Cohort Study. Ann Fam Med. 2020 Mar;18(2):131-138. doi: 10.1370/afm.2495.
citation: Frappe P, Cogneau J, Gaboreau Y, Abenhaim N, Bayen M, Calafiore M, Guichard C, Jacquet JP, Lacoin F, Bertoletti L; CACAO study investigators. Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice. PLoS One. 2017 Apr 6;12(4):e0175167. doi: 10.1371/journal.pone.0175167. eCollection 2017.