Low INR to Minimize Bleeding With Mechanical Valves Trial

Browse trials for

• Hemorrhage 1,383
• Thromboembolism 288

Keywords

• Mechanical valve replacement
• Vitamin K antagonist
• INR targets
• Bleeding
• Thromboembolism

Hemorrhage

1,383 studies on the registry are indexed under Hemorrhage; 244 are open to participants now.

This study's planned enrollment of 2,625 is above the median of 102 across 926 interventional studies indexed under Hemorrhage.

Lead sponsor

Population Health Research Institute is the lead sponsor of 115 studies on the registry; 26 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.

Study arms

• Experimental
  Reduced INR Target

  Warfarin therapy will be titrated to a target INR in the range of 1.5 to 2.5.

  Drug: Warfarin

• Active comparator
  Standard INR Target

  Warfarin therapy will be titrated to a "standard of care" target INR range.

  Drug: Warfarin

Interventions

• DrugWarfarin

  Participants in both arms will be on warfarin therapy post-mechanical valve replacement as is standard, but will have different INR target ranges.

  Also known as: Coumadin

Primary outcomes

1. Thrombosis/thromboembolism

   Number of patients who have at least one of the following: ischemic stroke, systemic thromboembolism, and valve thrombosis

   Time frame: Through study completion, an expected mean of 2-3 years

2. Major bleeding

   Number of patients that have bleeding that results in the following: 1. Death and/or, 2. Symptomatic bleeding in critical area or organ (e.g. intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, in a non-operated joint, or intramuscular with compartment syndrome) and/or, 3. Bleeding that causes drop of hemoglobin level by 20 g/L or more, or that requires the transfusion of 2 or more units of packed red blood cells or whole blood

   Time frame: Through study completion, an expected mean of 2-3 years

Secondary outcomes

1. All cause mortality

   Selected rather than cardiovascular mortality, as cause-specific mortality is often difficult to ascertain or define in complex cardiovascular patients in whom multi-end-organ dysfunction may accompany cardiovascular decline.

   Time frame: Through study completion, an expected mean of 2-3 years

2. All clinically important bleeding

   Number of patients that experience all clinically important bleeding (major and minor)

   Time frame: Through study completion, an expected mean of 2-3 years

3. Minor bleeding

   Number of patients that experience a bleed that does not meet major bleeding criteria

   Time frame: Through study completion, an expected mean of 2-3 years

4. All stroke

   Number of patients that experience a strokes, including ischemic stroke, ischemic with secondary transformation, stroke of uncertain classification and hemorrhagic stroke

   Time frame: Through study completion, an expected mean of 2-3 years

5. Ischemic stroke

   Number of patients that experience an ischemic stroke, defined as focal brain infarction caused by an arterial (or rarely venous) obstruction and as documented by CT/MRI that is normal or shows an infarct in the clinicall expected area

   Time frame: Through study completion, an expected mean of 2-3 years

6. Hemorrhagic stroke

   Number of patients that experience a hemorrhagic stroke, defined as requiring neuroimaging or autopsy confirmation, and includes two subcategories: primary intracerebral hemorrhage and primary subarachnoid hemorrhage

   Time frame: Through study completion, an expected mean of 2-3 years

7. Type 1, 2 or 3 myocardial infarction

   Number of patients who experience a type 1, 2 or 3 myocardial infarction

   Time frame: Through study completion, an expected mean of 2-3 years

8. Systemic thromboembolism

   Number of patients who experience a systemic thromboembolism

   Time frame: Through study completion, an expected mean of 2-3 years

9. Valve thrombosis

   Number of patients who experience a valve thrombosis

   Time frame: Through study completion, an expected mean of 2-3 years

10. Pulmonary embolism

    Number of patients who experience a pulmonary embolism

    Time frame: Through study completion, an expected mean of 2-3 years

11. Deep vein thrombosis

    Number of patients who experience a deep vein thrombosis

    Time frame: Through study completion, an expected mean of 2-3 years

12. New renal replacement therapy

    Number of patients requiring new renal replacement therapy

    Time frame: Through study completion, an expected mean of 2-3 years

13. Time in therapeutic range

    The percentage of time the patient's INR was within the target range

    Time frame: Through study completion, an expected mean of 2-3 years

14. Proportion of patients with extreme INR values (>4)

    The proportion of patients with at least one reported INR value above 4

    Time frame: Through study completion, an expected mean of 2-3 years

Publications

• Puskas J, Gerdisch M, Nichols D, Quinn R, Anderson C, Rhenman B, Fermin L, McGrath M, Kong B, Hughes C, Sethi G, Wait M, Martin T, Graeve A; PROACT Investigators. Reduced anticoagulation after mechanical aortic valve replacement: interim results from the prospective randomized on-X valve anticoagulation clinical trial randomized Food and Drug Administration investigational device exemption trial. J Thorac Cardiovasc Surg. 2014 Apr;147(4):1202-1210; discussion 1210-1. doi: 10.1016/j.jtcvs.2014.01.004. Epub 2014 Jan 12. PubMed 24512654 ↗
• Torella M, Torella D, Chiodini P, Franciulli M, Romano G, De Santo L, De Feo M, Amarelli C, Sasso FC, Salvatore T, Ellison GM, Indolfi C, Cotrufo M, Nappi G. LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial. Am Heart J. 2010 Jul;160(1):171-8. doi: 10.1016/j.ahj.2010.05.005. PubMed 20598989 ↗

Individual participant data

Plan to share: No — We will establish a plan for the full-scale study but there is no plan to make IPD available to other researchers.