3D-INTENSITY: D-Dimer Determined Anticoagulation INTENSITY in Patients With Mechanical Valve Replacement

• Sponsor: Wuhan Asia Heart Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01996657
• Collaborator: (none)
• Enrollment: 772
• Locations: 2
• Duration (Months): 41
• Patients Per Site: 386
• Patients Per Site Per Month: 9.4

Study Details

Study Description

Brief Summary

The optimal intensity of oral anticoagulation in China patients undergoing mechanical valve replacements is still controversial due to the different risk profiles of thrombophilia and bleeding in Chinese patients. Elevated D-dimer could reflect a pro-thrombogenic or prothrombotic state, and thus might be used to decide the intensity of oral anticoagulation.

This study was to evaluate whether elevated D-dimer levels could help to determine the intensity of oral anticoagulation in patients with mechanical heart valve prostheses.

Condition or Disease	Intervention/Treatment	Phase
Heart Valve Disease	Drug: Warfarin

Detailed Description

Background: The optimal intensity of oral anticoagulation in China patients undergoing mechanical valve replacements is still controversial due to the different risk profiles of thrombophilia and bleeding in Chinese patients. Elevated D-dimer could reflect a pro-thrombogenic or prothrombotic state, and thus might be used to decide the intensity of oral anticoagulation.

Objective: This study was to evaluate whether elevated D-dimer levels could help to determine the intensity of oral anticoagulation in patients with mechanical heart valve prostheses.

Methods: A single-center, prospective study was performed. 748 Patients with mechanical valve replacement who had received oral anticoagulation. The patients were randomly assigned to three groups The intensity of anticoagulation for group one was standard intensity (INR:2.5-3.5). The intensity of anticoagulation for group two was kept at low intensity without adjustment (INR:1.8-2.6), and for group three , The intensity of anticoagulation maintained at low level initiatively (INR:1.8-2.6), D-dimer testing were analyzed two times at 3 month later. In case of D-dimer level elevated, adjusted the intensity of anticoagulation to standard level. The endpoint of the study was the subsequent thromboembolic and major bleeding during an average follow-up of 2 years.

Study Design

• Study Type: Observational
• Actual Enrollment: 772 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: D-dimer Levels Determined the Intensity of Anticoagulation Therapy to Improve Outcomes in Patients With Mechanical Valve Replacement
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Standard intensity of anticoagulation After mechanical valve replacement，patients should be gave oral anticoagulants，such as warfarin.and The intensity of anticoagulation for this group was standard intensity (INR:2.5-3.5).	Drug: Warfarin; Other Names: Warfarin Sodium Tablets
Low intensity and adjusted by elevated D-dimer The intensity of anticoagulation maintained at low level initiatively, D-dimer testing were analyzed at 3 month later. In case of D-dimer level elevated, adjusted the intensity to standard level.	Drug: Warfarin; Other Names: Warfarin Sodium Tablets
Low intensity without adjustment The intensity of anticoagulation for this group was kept at low intensity without adjustment (INR:1.8-2.6),	Drug: Warfarin; Other Names: Warfarin Sodium Tablets

Outcome Measures

Primary Outcome Measures

1. Bleeding Events; [Up to 24 months]

   The bleeding events included cerebral hemorrhage, gastrointestinal bleeding and other major internal or external bleeding that causes death, hospitalization, or permanent injury (e.g. vision loss) or necessitates transfusion.

2. Thrombotic Events [24 months]

   The thrombotic events included valve thrombosis, transient ischemic attack, ischemic stroke, peripheral embolism, and myocardial infarction.

Secondary Outcome Measures

1. All Cause Deaths [Up to 24 months]

   The deaths from all causes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. age>18years,male or female without pregnancy;

2. Suffered the mechanical valves replacement in Wuhan Asia Heart Hospital;

3. The operation type was Mitral valve replacement or Double valves replacement(aortic and mitral valve replacement).

Exclusion Criteria: Patients with following diseases within 3 months.

1. deep venous thromboembolism

2. Pulmonary embolism

3. Aortic dissection

4. stroke

5. Cerebral hemorrhage

6. Myocardial infarction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	WAHH	Wuhan	Hubei	China	430000
2	Wuhan Asia Heart Hospital	Wuhan	Hubei	China	430022

Sponsors and Collaborators

• Wuhan Asia Heart Hospital

Investigators

• Study Director: zhang zhenlu, PH.D, Wuhan Asia Heart Hospital
• Study Chair: Zhou xin, Doctor, Wuhan Asia Heart Hospital
• Study Director: liu ze jin, PH.D, Wuhan Asia Heart Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wuhan Asia Heart Hospital
• ClinicalTrials.gov Identifier: NCT01996657
• Other Study ID Numbers: 2013-P-002
• First Posted: Nov 27, 2013
• Last Update Posted: Jun 26, 2017
• Last Verified: Jun 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Wuhan Asia Heart Hospital: mechanical valves replacement; INR; D-dimer; thromboembolic events
• Additional relevant MeSH terms: Heart Valve Diseases; Warfarin

Study Results

Participant Flow

Arm/Group Title	Standard Intensity of Anticoagulation	Low Intensity and Adjusted by Elevated D-dimer	Low Intensity Without Adjustment
Arm/Group Description	After mechanical valve replacement，patients should be gave oral anticoagulants，such as warfarin.and The intensity of anticoagulation for this group was standard intensity (INR:2.5-3.5). Warfarin	The intensity of anticoagulation maintained at low level initiatively, D-dimer testing were analyzed at 3 month later. In case of D-dimer level elevated, adjusted the intensity to standard level. Warfarin	The intensity of anticoagulation for this group was kept at low intensity without adjustment (INR:1.8-2.6), Warfarin
Period Title: Overall Study
STARTED	250	250	248
COMPLETED	237	239	234
NOT COMPLETED	13	11	14

Baseline Characteristics

Arm/Group Title	Standard Intensity of Anticoagulation	Low Intensity and Adjusted by Elevated D-dimer	Low Intensity Without Adjustment	Total
Arm/Group Description	After mechanical valve replacement，patients should be gave oral anticoagulants，such as warfarin.and The intensity of anticoagulation for this group was standard intensity (INR:2.5-3.5). Warfarin	The intensity of anticoagulation maintained at low level initiatively, D-dimer testing were analyzed at 3 month later. In case of D-dimer level elevated, adjusted the intensity to standard level. Warfarin	The intensity of anticoagulation for this group was kept at low intensity without adjustment (INR:1.8-2.6), Warfarin	Total of all reporting groups
Overall Participants	237	239	234	710
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	48.8 (11.5)	50.4 (11.9)	50.1 (10.9)	49.8 (11.3)
Sex: Female, Male (Count of Participants)
Female	113 47.7%	102 42.7%	96 41%	311 43.8%
Male	124 52.3%	137 57.3%	138 59%	399 56.2%
Elevated D-dimer(n) (participants) [Number]
Number [participants]	17 7.2%	36 15.1%	38 16.2%	91 12.8%

Outcome Measures

1. Primary Outcome

Title	Bleeding Events;
Description	The bleeding events included cerebral hemorrhage, gastrointestinal bleeding and other major internal or external bleeding that causes death, hospitalization, or permanent injury (e.g. vision loss) or necessitates transfusion.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Intensity of Anticoagulation	Low Intensity and Adjusted by Elevated D-dimer	Low Intensity Without Adjustment
Arm/Group Description	After mechanical valve replacement，patients should be gave oral anticoagulants，such as warfarin.and The intensity of anticoagulation for this group was standard intensity (INR:2.5-3.5). Warfarin	The intensity of anticoagulation maintained at low level initiatively, D-dimer testing were analyzed at 3 month later. In case of D-dimer level elevated, adjusted the intensity to standard level. Warfarin	The intensity of anticoagulation for this group was kept at low intensity without adjustment (INR:1.8-2.6), Warfarin
Measure Participants	237	239	234
Count of Participants [Participants]	16 6.8%	3 1.3%	4 1.7%

2. Primary Outcome

Title	Thrombotic Events
Description	The thrombotic events included valve thrombosis, transient ischemic attack, ischemic stroke, peripheral embolism, and myocardial infarction.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Intensity of Anticoagulation	Low Intensity and Adjusted by Elevated D-dimer	Low Intensity Without Adjustment
Arm/Group Description	After mechanical valve replacement，patients should be gave oral anticoagulants，such as warfarin.and The intensity of anticoagulation for this group was standard intensity (INR:2.5-3.5). Warfarin	The intensity of anticoagulation maintained at low level initiatively, D-dimer testing were analyzed at 3 month later. In case of D-dimer level elevated, adjusted the intensity to standard level. Warfarin	The intensity of anticoagulation for this group was kept at low intensity without adjustment (INR:1.8-2.6), Warfarin
Measure Participants	237	239	234
Count of Participants [Participants]	5 2.1%	5 2.1%	14 6%

3. Secondary Outcome

Title	All Cause Deaths
Description	The deaths from all causes
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Intensity of Anticoagulation	Low Intensity and Adjusted by Elevated D-dimer	Low Intensity Without Adjustment
Arm/Group Description	After mechanical valve replacement，patients should be gave oral anticoagulants，such as warfarin.and The intensity of anticoagulation for this group was standard intensity (INR:2.5-3.5). Warfarin	The intensity of anticoagulation maintained at low level initiatively, D-dimer testing were analyzed at 3 month later. In case of D-dimer level elevated, adjusted the intensity to standard level. Warfarin	The intensity of anticoagulation for this group was kept at low intensity without adjustment (INR:1.8-2.6), Warfarin
Measure Participants	237	239	234
Count of Participants [Participants]	12 5.1%	4 1.7%	5 2.1%

Adverse Events

Arm/Group Title	Standard Intensity of Anticoagulation		D-dimer-guided Adjustmentd of Anticoagutlation Intensity		Low Intensity Without Adjustment
Arm/Group Description	After mechanical valve replacement，patients should be gave oral anticoagulants，such as warfarin.and The intensity of anticoagulation for this group was standard intensity (INR:2.5-3.5). Warfarin		The intensity of anticoagulation maintained at low level initiatively, D-dimer testing were analyzed at 3 month later. In case of D-dimer level elevated, adjusted the intensity to standard level. Warfarin		The intensity of anticoagulation for this group was kept at low intensity without adjustment (INR:1.8-2.6), Warfarin
All Cause Mortality
	Standard Intensity of Anticoagulation		D-dimer-guided Adjustmentd of Anticoagutlation Intensity		Low Intensity Without Adjustment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/245 (4.9%)		4/245 (1.6%)		5/242 (2.1%)
Serious Adverse Events
	Standard Intensity of Anticoagulation		D-dimer-guided Adjustmentd of Anticoagutlation Intensity		Low Intensity Without Adjustment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/245 (9.8%)		9/245 (3.7%)		20/242 (8.3%)
Blood and lymphatic system disorders
thrombotic envents	5/245 (2%)		5/245 (2%)		14/242 (5.8%)
bleeding events	16/245 (6.5%)		3/245 (1.2%)		4/242 (1.7%)
Cardiac disorders
Deaths from other causes	3/245 (1.2%)		1/245 (0.4%)		2/242 (0.8%)
Other (Not Including Serious) Adverse Events
	Standard Intensity of Anticoagulation		D-dimer-guided Adjustmentd of Anticoagutlation Intensity		Low Intensity Without Adjustment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/245 (0%)		0/245 (0%)		0/242 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.