Very Low Dose Oral Anticoagulation and Thromboembolic and Bleeding Complications (ESCAT III)

Effects of Very Low Dose Oral Anticoagulation on Thromboembolism and Bleeding Events in Patients With Mechanical Heart Valve Replacement

We aim to investiagte whether very low dose self management of oral anticoagulation is superior to low dose oral anticoagulation in order to prevent bleeding events in patients undergoing mechanuical heart valve replacement.

Study Overview

• Status: Terminated
• Conditions: Mechanical Heart Valve Recipients
• Intervention / Treatment: Drug: phenprocoumon; Drug: phenprocoumon; Drug: phenprocoumon

Detailed Description

In mechanical heart valve recipients, self-management of oral anticoagulation can reduce the risk of developing thromboembolic events and improves long-term survival compared with international normalized ratio (INR) control by a general practitioner. Low-dose INR self-management (INR values of 1.8.-2.8 for aortic valve recipients and 2.5 - 3.5 for mitral or double valve recipients) does not increase the risk of thromboembolic events compared to conventional dose INR self-management. Even in patients with a low INR target range, however, the risk of bleeding events is still higher than the risk of thromboembolism. We therefore perform a prospective, randomized trial in 1,800 patients with mechanical heart valve replacement. During the first six postoperative months, low dose INR self-management will be performed by all patients (INR measurement once a week). Thereafter, 600 patients will continue with this treatment regimen, whereas the other 1,200 patients with perform very low dose oral anticoagulation. Out of these 1,200 patients, 600 will perform INR measurement once a week and 600 patients will perform INR measurement twice a week. Patients are followed up for 24 months.

• Study Type: Interventional
• Enrollment (Actual): 1571
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bad Oeynhausen, Germany, 32545
    • Heart and Diabetes Center NRW

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Mechanical heart valve recipients

Exclusion Criteria:

• Contra-indication to phenprocoumon
• Ulcerous disease with bleeding tendency,
• Hypo- or hypercoagulability
• Dementia
• Missing informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Low dose oral anticoagulation, INR self-management once a week	Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.8 - 2.8 for aortic valve recipients and 2.5 - 3.5 for mitral or double valve recipients, INR-self management once a week; Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.6-2.1 for aortic valve recipients and 2.0 - 2.5 for mitral or double valve recipients, INR self management once a week; Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.6-2.1 for aortic valve recipients and 2.0 - 2.5 for mitral or double valve recipients, INR self management twice a week
Active Comparator: B; very low dose oral anticoagulation, INR self-management once a week	Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.8 - 2.8 for aortic valve recipients and 2.5 - 3.5 for mitral or double valve recipients, INR-self management once a week; Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.6-2.1 for aortic valve recipients and 2.0 - 2.5 for mitral or double valve recipients, INR self management once a week; Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.6-2.1 for aortic valve recipients and 2.0 - 2.5 for mitral or double valve recipients, INR self management twice a week
Experimental: C; very low dose oral anticoagulation, INR self-management twice a week	Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.8 - 2.8 for aortic valve recipients and 2.5 - 3.5 for mitral or double valve recipients, INR-self management once a week; Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.6-2.1 for aortic valve recipients and 2.0 - 2.5 for mitral or double valve recipients, INR self management once a week; Drug: phenprocoumon; The daily phenprocoumon dose administered should achieve an international normalized ratio (INR) of 1.6-2.1 for aortic valve recipients and 2.0 - 2.5 for mitral or double valve recipients, INR self management twice a week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Thromboembolic events, Bleeding events, Survival rates	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
INR values, Percent of INR values in the target range	2 years

Collaborators and Investigators

• Sponsor: Heart and Diabetes Center North-Rhine Westfalia
• Collaborators: Klinikum Ludwigshafen; University of Kiel
• Investigators: Principal Investigator: Heinrich Koertke, MD, Institute of Applied Telemedicine, Heart and Diabetes Center North-Rhine Westfalia, 32545 Bad Oeynhausen, Germany

Publications and helpful links

General Publications

• Koertke H, Minami K, Boethig D, Breymann T, Seifert D, Wagner O, Atmacha N, Krian A, Ennker J, Taborski U, Klovekorn WP, Moosdorf R, Saggau W, Koerfer R. INR self-management permits lower anticoagulation levels after mechanical heart valve replacement. Circulation. 2003 Sep 9;108 Suppl 1:II75-8. doi: 10.1161/01.cir.0000089185.80318.3f.
• Koertke H, Zittermann A, Wagner O, Koerfer R. Self-management of oral anticoagulation therapy improves long-term survival in patients with mechanical heart valve replacement. Ann Thorac Surg. 2007 Jan;83(1):24-9. doi: 10.1016/j.athoracsur.2006.08.036.
• Koertke H, Zittermann A, Mommertz S, El-Arousy M, Litmathe J, Koerfer R. The Bad Oeynhausen concept of INR self-management. J Thromb Thrombolysis. 2005 Feb;19(1):25-31. doi: 10.1007/s11239-005-0937-1.
• Koertke H, Zittermann A, Minami K, Tenderich G, Wagner O, El-Arousy M, Krian A, Ennker J, Taborski U, Klovekorn WP, Moosdorf R, Saggau W, Morshuis M, Koerfer J, Seifert D, Koerfer R. Low-dose international normalized ratio self-management: a promising tool to achieve low complication rates after mechanical heart valve replacement. Ann Thorac Surg. 2005 Jun;79(6):1909-14; discussion 1914. doi: 10.1016/j.athoracsur.2004.09.012.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 11, 2007
• First Submitted That Met QC Criteria: September 11, 2007
• First Posted (Estimate): September 12, 2007

Study Record Updates

• Last Update Posted (Estimate): December 11, 2013
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: phenprocoumon; INR self-management; mechanical heart valve replacement; bleeding; thromboembolism
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Anticoagulants; Phenprocoumon
• Other Study ID Numbers: 002 (University of CT Health Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No