Evaluation of Oral Anticoagulation With Vitamin K Antagonists - The thrombEVAL Study Programme (thrombEVAL)

A Study Programme for the Evaluation of Oral Anticoagulation Therapy With Vitamin K Antagonists

Since decades, oral anticoagulation (OAC) with vitamin K antagonists (VKA) is an established therapy for both prevention and treatment of thromboembolism in daily clinical routine. Increasing life-expectancy, the demographic change and novel oral anticoagulants lead to an increasing complexity of medical therapy. However, data on quality and management of VKA therapy with phenprocoumon in current medical care are limited. Our aim was to investigate the quality of OAC with VKA in current health care and to evaluate the potential for improvements.

The investigator-initiated thrombEVAL study program comprises two cohorts of patients treated with vitamin K antagonists for oral anticoagulation therapy in real-life settings: a multicentre cohort of patients in regular medical care and a multi-local, single centre cohort of patients in a telemedicine-based coagulation service. The study program is expected to enrol a total number of approximately 2,000 to 2,500 patients. Both cohorts build on a detailed clinical assessment of participants and anticoagulation therapy at study enrolment. Subsequently active and passive follow-up investigations are carried out to document and validate complications of the treatment. Primary short-term outcome is the distribution of time in therapeutic range; the primary long-term outcome comprises the composite of stroke, systemic embolism, myocardial infarction, major and clinically-relevant bleeding and death.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Venous Thromboembolism; Anticoagulant Antagonists, Vitamin K and Other Coagulants Causing Adverse Effects in Therapeutic Use

• Study Type: Observational
• Enrollment (Actual): 2318

Contacts and Locations

Study Locations

• Germany
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • University Medical Center of the Johannes Gutenberg University Mainz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

In cohort A, patients of regular medical care are enrolled in the area of Rhineland-Palatinate, Germany. Treatment and management of oral anticoagulation therapy with vitamin K antagonists is performed within primary (ambulatory) care system.

In cohort B, patients are treated with oral anticoagulation in a specialized telemedicine-based coagulation service in the area of Rhinehesse, Germany.

Description

Inclusion Criteria

1. Age ≥ 18 years of age at study inclusion
2. Written informed consent by patient or legal guardian, if appointed
3. Cohort A: Pretreatment with oral anticoagulation therapy with vitamin K antagonists (VKA) for at least 4 months in regular medical care including patients with self-management of oral anticoagulation therapy
4. Cohort B: Indication for oral anticoagulation therapy with VKA for at least 3 months (both drug-naive and -experienced patients) at enrolment including patients with self-management of oral anticoagulation therapy.

Exclusion Criteria

1. Contraindication to VKA treatment, e.g. pregnancy or known hypersensitivity
2. Participation in other clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort A: Regular medical care; Patients treated with vitamin K antagonists in regular medical care system
Cohort B: Coagulation service; Patients with oral anticoagulation therapy in a telemedicine-based coagulation service

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in therapeutic range	Time in therapeutic range for the International Normalized Ratio as measured by linear interpolation method	Assessment during Year 1 after study enrolment
Hospitalisation	Any Hospitalisation	Assessment at year 1 and 2 after study enrolment
Net clinical benefit	Composite of stroke, systemic embolism, pulmonary embolism, myocardial infarction, major and clinically relevant, non-major bleeding and death	Assessment at year 1 and 2

Collaborators and Investigators

• Sponsor: Johannes Gutenberg University Mainz
• Collaborators: Sanofi; Bayer; Boehringer Ingelheim; German Federal Ministry of Education and Research; The German Heart Foundation; Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company; Ministry of Health, Rhineland-Palatinate, Germany; Ministry of Economics, Rhineland-Palatinate, Germany; IMO Institut GmbH; PortaVita BV
• Investigators: Principal Investigator: Philipp S Wild, MD, MSc, University Medical Center of Johannes Gutenberg-University Mainz, Germany; Principal Investigator: Thomas F Munzel, MD, University Medical Center of Johannes Gutenberg-University Mainz, Germany

Publications and helpful links

General Publications

• Keller K, Prochaska JH, Coldewey M, Gobel S, Schmitt VH, Hahad O, Ullmann A, Nagler M, Lamparter H, Espinola-Klein C, Munzel T, Wild PS. Atherosclerosis and Its Impact on the Outcomes of Patients with Deep Venous Thrombosis. Life (Basel). 2022 May 14;12(5):734. doi: 10.3390/life12050734.
• Eggebrecht L, Ludolph P, Gobel S, Panova-Noeva M, Arnold N, Nagler M, Bickel C, Lauterbach M, Hardt R, Cate HT, Lackner KJ, Espinola-Klein C, Munzel T, Prochaska JH, Wild PS. Cost saving analysis of specialized, eHealth-based management of patients receiving oral anticoagulation therapy: Results from the thrombEVAL study. Sci Rep. 2021 Jan 28;11(1):2577. doi: 10.1038/s41598-021-82076-9.
• Michal M, Eggebrecht L, Gobel S, Panova-Noeva M, Nagler M, Arnold N, Lauterbach M, Bickel C, Wiltink J, Beutel ME, Munzel T, Wild PS, Prochaska JH. The relevance of depressive symptoms for the outcome of patients receiving vitamin K antagonists: results from the thrombEVAL cohort study. Eur Heart J Cardiovasc Pharmacother. 2021 Jul 23;7(4):271-279. doi: 10.1093/ehjcvp/pvz085.
• Prochaska JH, Gobel S, Nagler M, Knopfler T, Eggebrecht L, Lamparter H, Panova-Noeva M, Keller K, Coldewey M, Bickel C, Lauterbach M, Hardt R, Espinola-Klein C, Ten Cate H, Rostock T, Munzel T, Wild PS. Sustained atrial fibrillation increases the risk of anticoagulation-related bleeding in heart failure. Clin Res Cardiol. 2018 Dec;107(12):1170-1179. doi: 10.1007/s00392-018-1293-4. Epub 2018 Jun 9.
• Prochaska JH, Gobel S, Keller K, Coldewey M, Ullmann A, Lamparter H, Schulz A, Schinzel H, Bickel C, Lauterbach M, Michal M, Hardt R, Binder H, Espinola-Klein C, Lackner KJ, Ten Cate H, Munzel T, Wild PS. e-Health-based management of patients receiving oral anticoagulation therapy: results from the observational thrombEVAL study. J Thromb Haemost. 2017 Jul;15(7):1375-1385. doi: 10.1111/jth.13727. Epub 2017 Jun 6.
• Keller K, Prochaska JH, Coldewey M, Gobel S, Ullmann A, Junger C, Lamparter H, Ariza L, Bickel C, Lauterbach M, Konstantinides S, Rostock T, Munzel T, Wild PS. History of deep vein thrombosis is a discriminator for concomitant atrial fibrillation in pulmonary embolism. Thromb Res. 2015 Nov;136(5):899-906. doi: 10.1016/j.thromres.2015.08.024. Epub 2015 Sep 3.
• Prochaska JH, Gobel S, Keller K, Coldewey M, Ullmann A, Lamparter H, Junger C, Al-Bayati Z, Baer C, Walter U, Bickel C, ten Cate H, Munzel T, Wild PS. Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL. BMC Med. 2015 Jan 23;13:14. doi: 10.1186/s12916-015-0268-9.
• Prochaska JH, Coldewey M, Gobel S, Keller K, Hendelmeier M, Konstantinides S, Munzel T, Wild PS; thrombEVAL Study Group. Evaluation of oral anticoagulation therapy: rationale and design of the thrombEVAL study programme. Eur J Prev Cardiol. 2015 May;22(5):622-8. doi: 10.1177/2047487314527852. Epub 2014 Mar 31.

Helpful Links

• Study information homepage

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: March 8, 2013
• First Submitted That Met QC Criteria: March 8, 2013
• First Posted (Estimate): March 12, 2013

Study Record Updates

• Last Update Posted (Actual): August 24, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Bypass surgery; Venous thromboembolism; Oral Anticoagulation; Prosthetic heart valve; Regular Medical Care; Coagulation Service; Vitamin-K Antagonists; Quality of therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Arrhythmias, Cardiac; Atrial Fibrillation; Thromboembolism; Venous Thromboembolism
• Other Study ID Numbers: UMCM-2010EPI01