The Home INR Study

Study Overview
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Brief Summary
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Since home monitors of prothrombin time (PT) may potentially improve the safety, quality, and convenience of chronic anticoagulation management, it is likely that there will be demands from providers, patients, and manufacturers to make home monitors available to VA patients. The rationale for patient self-testing (PST) is that, compared to conventional high quality anticoagulation management (HQACM), it would permit more intense monitoring and increased patient participation in his/her own care, resulting in increased precision in anticoagulation control and thus fewer events of thromboembolism (strokes) and bleeding. The secondary hypothesis is that PST and HQACM will be comparable in terms of health care utilization and cost.

Detailed Description
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Intervention: Weekly patient self-testing (PST) of prothrombin time by international normalized ratio (PT INR) versus conventional monthly high quality anticoagulation management (HQACM) from an anticoagulation clinic with a minimum two years follow-up. Primary Hypothesis: Compared to conventional monitoring in the clinic, PST of anticoagulation intensity will decrease the number of events of thromboembolism (strokes), bleeding, and all cause deaths and improve the quality of anticoagulation. Second Hypothesis: PST and conventional monitoring will be comparable in terms of health care utilization and cost. Primary Outcomes: Event rates (thromboembolism or bleeding episodes), time to first event, time within therapeutic range for anticoagulation intensity, and total health care cost (including price of PST monitors) and utilization. Study Abstract: Since home monitors of prothrombin time (PT) may potentially improve the safety, quality, and convenience of chronic anticoagulation management, it is likely that there will be demands from providers, patients, and manufacturers to make home monitors available to VA patients. The rationale for PST is that it would permit more intense monitoring and increased patient participation in his/her own care, resulting in increased precision in anticoagulation control and thus fewer events. Original plan was for a study at 32 sites with a total sample size of about 3,200 patients and a length of three years (one for recruitment and two years of follow-up). Final status was 28 sites that randomized 2922 patients in 2.75 years of recruitment with a minimum of two years of follow-up.

Official Title
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CSP #481 - The Home INR Study (THINRS)

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Procedure: Weekly patient self-testing of prothrombin time
* Other: High quality anticoagulation management (HQACM) with conventional monthly testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be enrolled in this study, patients must: have AF and/or a MHV; be scheduled to receive warfarin indefinitely (operationally defined as 2 years); be using warfarin according to the criteria described in the Coumadin package insert (no off-label uses); be expected to survive for the duration of the study; not be suffering from intracranial bleeding (intracranial hemorrhage, subarachnoid hemorrhage, hemorrhagic stroke) or any other contraindication described in the Coumadin package insert; be willing to perform PST; be willing to be randomized; possess adequate cognitive and language skills to follow the protocol and all related instructions; be willing to participate for the full duration of the study; sign the informed consent form; and not be enrolled in another randomized clinical trial that involves a drug or device intervention. Exclusion Criteria: Patients are excluded in this study if: subject has had intracranial hemorrhage, subarachnoid hemorrhage, hemorrhagic stroke, or any other absolute/major contraindication described in the warfarin package insert within the last month subject enrolled in another randomized clinical trial that involves a drug or device intervention subject is not able to follow the protocol and all related instructions, and does not have a caregiver with these skills

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Patient Self-Testing (PST) of prothrombin time by international normalized ratio (PT-INR or INR) with weekly testing | Procedure: Weekly patient self-testing of prothrombin time<br> <br> |
| Other: Arm 2<br>High quality anticoagulation management (HQACM) with conventional monthly testing | Other: High quality anticoagulation management (HQACM) with conventional monthly testing<br>* HQACM with testing every 4 weeks and as indicated for out of range values, medication/clinical changes.<br>* Other names: HQACM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Event (Death, Stroke, Major Bleed) | Time to first event (death, stroke, major bleed) The primary outcome was time to first event, and we used the Kaplan-Meier method to compare survival curves and the results using the log-rank test. The number of patients with a primary outcome is what was reported in the NEJM paper. Below is the unpublished cumulative incidence information. | Time to event | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in Therapeutic Range Over Full Length of Follow-up (0 to 100 Percent) | Time in target range (TTR) based on Prothrombin Time standardized to the International Normalized Ratio | Full length of follow-up; average of 3 years | 
| DASS at 2 Years of Follow-up | Satisfaction with care was quantified using the Duke Anticoagulation Satisfaction Scale (DASS). Scores range from 25 to 225, with lower scores indicating higher satisfaction. | At two years of follow-up | 
| Cumulative Gain in Health Utilities at 2 Year | Scores range from -0.36 to 1.00 per year, with a negative score indicating a state worse than being dead and a score of 1.00 indicating perfect health. Since the time frame is 2 years, the range is -0.72 to 2.00. | After 2 years of follow-up for each subject | 
| Health Care Costs at 2 Year |  | After 2 years of follow-up for each subject | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AF, Mechanical heart valve (MHV)