Atrial Fibrillation
Conditions
Keywords
AF, Mechanical heart valve (MHV)
Brief summary
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
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.
Interventions
PROCEDUREWeekly patient self-testing of prothrombin time
OTHERHigh quality anticoagulation management (HQACM) with conventional monthly testing
HQACM with testing every 4 weeks and as indicated for out of range values, medication/clinical changes.
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be enrolled in this study, patients must: 1. have AF and/or a MHV; 2. be scheduled to receive warfarin indefinitely (operationally defined as 2 years); 3. be using warfarin according to the criteria described in the Coumadin package insert (no off-label uses); 4. be expected to survive for the duration of the study; 5. not be suffering from intracranial bleeding (intracranial hemorrhage, subarachnoid hemorrhage, hemorrhagic stroke) or any other contraindication described in the Coumadin package insert; 6. be willing to perform PST; 7. be willing to be randomized; 8. possess adequate cognitive and language skills to follow the protocol and all related instructions; 9. be willing to participate for the full duration of the study; 10. sign the informed consent form; and 11. not be enrolled in another randomized clinical trial that involves a drug or device intervention.
Exclusion criteria
Patients are excluded in this study if: 1. 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 2. subject enrolled in another randomized clinical trial that involves a drug or device intervention 3. subject is not able to follow the protocol and all related instructions, and does not have a caregiver with these skills
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Event (Death, Stroke, Major Bleed) | Time to event | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time in Therapeutic Range Over Full Length of Follow-up (0 to 100 Percent) | Full length of follow-up; average of 3 years | Time in target range (TTR) based on Prothrombin Time standardized to the International Normalized Ratio |
| DASS at 2 Years of Follow-up | At two 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. |
| Cumulative Gain in Health Utilities at 2 Year | After 2 years of follow-up for each subject | 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. |
| Health Care Costs at 2 Year | After 2 years of follow-up for each subject | — |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Recruitment started in August 2003 and ended at the end of May 2006. Participating sites were VA Medical Centers with anticoagulation services with active rosters of more than 400 patients.
Pre-assignment details
A total of 3745 participants were consented and screened. Out of this total, 823 were excluded from the study. The majority of those excluded is due to participants not doing or passing the competency assessment.
Participants by arm
| Arm | Count |
|---|---|
| Patient Self-Testing (PST) Patient Self-Testing (PST) of prothrombin time by international normalized ratio (PT-INR or INR) with weekly testing | 1,465 |
| High Quality Anticoagulation Management (HQACM) High quality anticoagulation management (HQACM) with conventional monthly testing | 1,457 |
| Total | 2,922 |
Baseline characteristics
| Characteristic | Patient Self-Testing (PST) | High Quality Anticoagulation Management (HQACM) | Total |
|---|---|---|---|
| Age, Continuous Total study population | 66.6 years STANDARD_DEVIATION 9.7 | 67.4 years STANDARD_DEVIATION 9.4 | 67 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 25 Participants | 26 Participants | 51 Participants |
| Sex: Female, Male Male | 1440 Participants | 1431 Participants | 2871 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 399 / 1,465 | 332 / 1,457 |
| serious Total, serious adverse events | 247 / 1,465 | 250 / 1,457 |
Outcome results
Primary
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 frame: Time to event
Population: Randomized participants with at least one day of follow-up, per intent to treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patient Self-Testing (PST) | Time to First Event (Death, Stroke, Major Bleed) | Cumulative Incidence at 500 Days | 0.0785 cumulative probability of event |
| Patient Self-Testing (PST) | Time to First Event (Death, Stroke, Major Bleed) | Cumulative Incidence at 1000 Days | 0.1542 cumulative probability of event |
| Patient Self-Testing (PST) | Time to First Event (Death, Stroke, Major Bleed) | Cumulative Incidence at 1500 Days | 0.2268 cumulative probability of event |
| High Quality Anticoagulation Management (HQACM) | Time to First Event (Death, Stroke, Major Bleed) | Cumulative Incidence at 500 Days | 0.0987 cumulative probability of event |
| High Quality Anticoagulation Management (HQACM) | Time to First Event (Death, Stroke, Major Bleed) | Cumulative Incidence at 1000 Days | 0.1820 cumulative probability of event |
| High Quality Anticoagulation Management (HQACM) | Time to First Event (Death, Stroke, Major Bleed) | Cumulative Incidence at 1500 Days | 0.2524 cumulative probability of event |
Comparison: The null hypothesis was the hazard ratio was equal to 1.p-value: 0.14Log Rank
Secondary
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.
Time frame: After 2 years of follow-up for each subject
Population: Randomized participants with at least one day of follow-up, per intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient Self-Testing (PST) | Cumulative Gain in Health Utilities at 2 Year | 1.204 score | Standard Deviation 0.619 |
| High Quality Anticoagulation Management (HQACM) | Cumulative Gain in Health Utilities at 2 Year | 1.049 score | Standard Deviation 0.575 |
Secondary
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.
Time frame: At two years of follow-up
Population: Randomized participants with at least one day of follow-up, per intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient Self-Testing (PST) | DASS at 2 Years of Follow-up | 46.8 score | Standard Deviation 16.3 |
| High Quality Anticoagulation Management (HQACM) | DASS at 2 Years of Follow-up | 49.2 score | Standard Deviation 18 |
Secondary
Health Care Costs at 2 Year
Time frame: After 2 years of follow-up for each subject
Population: Randomized participants with at least one day of follow-up, per intent to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Patient Self-Testing (PST) | Health Care Costs at 2 Year | 25,754 U.S. Dollars |
| High Quality Anticoagulation Management (HQACM) | Health Care Costs at 2 Year | 24,505 U.S. Dollars |
Secondary
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
Time frame: Full length of follow-up; average of 3 years
Population: Randomized participants with at least one day of follow-up, per intent to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patient Self-Testing (PST) | Time in Therapeutic Range Over Full Length of Follow-up (0 to 100 Percent) | 66.2 percentage | Standard Deviation 14.2 |
| High Quality Anticoagulation Management (HQACM) | Time in Therapeutic Range Over Full Length of Follow-up (0 to 100 Percent) | 62.4 percentage | Standard Deviation 17.1 |