Weekly Monitoring Strategy of Capillary INR Versus Monthly Monitoring Strategy of Venous INR in Elderly Patients in a Nursing Home.

Study Overview
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Brief Summary
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This primary care study aims to compare the time in therapeutic range (TTR) of two strategies for monitoring the international normalized ratio (INR) over 6 months in nursing homes. The population consists of frail elderly patients for whom Anti-Vitamin K treatments are frequent, and who are consequently more prone to embolic and hemorrhagic complications.

Detailed Description
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Biological monitoring is essential to avoid strokes, deep vein thrombosis and hemorrhage. Generally speaking, this consists of a venous sampling for the international normalized ratio (INR), for which the therapeutic target is approximately 2.5 (tolerance range between 2 and 3) for atrial fibrillation (AF) and deep vein thrombosis (DVT). INR values below 2 indicate high risks of a stroke or DVT, whereas INR values over 3 refer to high risks of hemorrhage. INR monitoring requires monthly follow-ups or even more frequently if the HAS BLED score is ≥ 3. One parameter used to evaluate the benefit/risk ratio is the time in therapeutic range (TTR), referring to the time spent within the INR therapeutic target (INR between 2 and 3 for patients with Atrial Fibrillation/ Deep Vein Thrombosis). It is calculated using the Rosendaal method. According to the European Society of Cardiology guidelines, the minimum threshold necessary for a good risk/benefit ratio is 70%. In other countries, it has been shown that the TTR is higher: 61% in Canada, 64.4% in Spain, 68.9% in Italy and 76.2% in Sweden. Moreover, TTR determines the benefit/risk ratio of the treatment, which means that patients with a TTR < 60% have more than 2% absolute total mortality per patient-year compared to patients with TTR > 60%. As for the pilot study (Manuscript accepted in August 2019 in the Journal of Internal Medicine ), we expect approximately half the patients to be aged over 90. Patients will be recruited in nursing homes where they are monitored by nurses and care quality managers who are responsible for ensuring compliance with good clinical practices. This limits the risk of non-compliance with preanalytical venous INR conditions. Eighteen percent of subjects over 85 are treated with vitamin-K antagonists (VKA). For elderly patients with atrial fibrillation (AF) or deep venous thrombosis (DVT), stroke prophylaxis is a real clinical challenge. VKA treatments are indicated for the prevention of strokes in patients with Atrial Fibrillation, DVT or those who have received heart valve implants. VKAs have a narrow therapeutic range: if they are under-dosed, the risk of embolism (AVC and DVT) is high, whereas in the event of an overdose, the risk of bleeding is high. Given the annual incidence of severe hemorrhage (3-5%), the risk of a hemorrhage is their main side effect. The incidence of brain hemorrhages is 0.6 per 100 patient-years, for gastrointestinal bleeding it is 1.0 per 100 patient-years, and the risk of other serious bleeding is 1.4 per 100 patient-years. This risk of bleeding is usually assessed using the HAS-BLED score. The risk of hemorrhage is 4.2% per year in patients over 75 versus 1.7% per year for those under 75. Following the results of a pilot study (manuscript accepted in the Journal of Internal Medecine), the hypothesis is that a weekly monitoring strategy for capillary INR should increase the TTR of nursing home patients by 12% compared to the usual monitoring by venous INR, resulting in a decrease of thrombotic or hemorrhagic events.

Official Title
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Assessment of Weekly Monitoring Strategy of Capillary INR Versus Monthly Monitoring Strategy of Venous INR in Elderly Patients in a Nursing Home: Multicentre Randomised Cluster Trial.

Conditions
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Atrial Fibrillation, Deep Vein Thrombosis, Stroke

Intervention / Treatment
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* Device: Weekly monitoring using the capillary International Normalised Ratio strategy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The population corresponds to nursing homes patients treated with Vitamin K Antagonists for more than six months, because INRc cannot be used while anticoagulation treatment is being introduced. The patient or his/her trusted-person/legal representative/tutor signed the consent form The patient is an adult and lives in a nursing home The patient has been on treatment with Vitamin K Antagonists for more than six months The patient's target INR range is 2,5 [2-3] or 3 [2,5-3,5] The patient is affiliated to a health insurance program Exclusion Criteria: The patient is participating in a Type 1 interventional study involving human beings (Jardé law). The patient is in an exclusion period determined by another study The patient is under safeguard of justice. It is not possible to give the patient (or his/her trusted-person/legal representative/tutor) informed information. The patient has a short life expectancy (< 1 month) The Karnofky index is ≤ 20%

Ages Eligible for Study
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Minimum Age: 60 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is interventional, prospective, comparative, superiority, multicentric, randomised by cluster, in closed cohort.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: CONTROL GROUP<br>Control group (n = 16 nursing homes, 64 patients): Patients will be monitored as usual using the Venous International Normalised Ratio strategy. Practices will not be changed (i.e. prospective observation of real-life practices; according to recommendations, at least 1 Venous International Normalised Ratio per month will usually be performed) and patients will not receive any supplementary intervention specific to the trial. A reminder of good International Normalised Ratio practices will be provided to nurses and prescribers. | |
| Experimental: INTERVENTIONAL GROUP<br>Intervention group (n = 16 nursing homes, 64 patients): Patients in the interventional group will be monitored using the capillary International Normalised Ratio strategy every week, and more often if the International Normalised Ratio is not in the therapeutic target. Venous International Normalised Ratio punctures will also be performed as described for the control group in order to calculate the Time in Therapeutic Range equivalently in both groups. Specific training in handling the device and the dose adjustment protocol will be provided to nurses and prescribers. | Device: Weekly monitoring using the capillary International Normalised Ratio strategy<br>* Patients in the interventional group will be monitored using the capillary International Normalised Ratio strategy every week, and more often if the International Normalised Ratio is not in the therapeutic target. Venous International Normalised Ratio punctures will also be performed as described for the control group in order to calculate the Time in Therapeutic Range equivalently in both groups. Specific training in handling the device and the dose adjustment protocol will be provided to nurses and prescribers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interventional group : Time in Therapeutic Range using the capillary International Normalized Range weekly monitoring strategy | The CoaguChek INRange® device will be used. This small, portable monitoring medical device has already been used in several studies and can be used in hospital beds. After washing the patient's hands, the nurse will insert the strip test into the device, massaging the fingers and hand to activate blood circulation, and perform a capillary puncture using the lancet. An 8 μL drop of blood is required and must be deposited on the test strip less than 180 seconds after inserting the strip into the device and within 15 seconds after the start of blood drop formation. The International Normalized Ratio is displayed within one minute. When the nurse has the result, he/she will complete the VKA dose software (i.e. puncture number, strip number, current VKA type, current VKA dose, INRc value). The software will give the next puncture day and the correct VKA dose. If the INR > 4, there will be an alert and the nurse will have to contact the general practitioner for the rest of the procedure. | Day 0 | 
| Interventional group : Time in Therapeutic Range using the capillary International Normalized Range weekly monitoring strategy | The CoaguChek INRange® device will be used. This small, portable monitoring medical device has already been used in several studies and can be used in hospital beds. After washing the patient's hands, the nurse will insert the strip test into the device, massaging the fingers and hand to activate blood circulation, and perform a capillary puncture using the lancet. An 8 μL drop of blood is required and must be deposited on the test strip less than 180 seconds after inserting the strip into the device and within 15 seconds after the start of blood drop formation. The International Normalized Ratio is displayed within one minute. When the nurse has the result, he/she will complete the VKA dose software (i.e. puncture number, strip number, current VKA type, current VKA dose, INRc value). The software will give the next puncture day and the correct VKA dose. If the INR > 4, there will be an alert and the nurse will have to contact the general practitioner for the rest of the procedure. | Month 6 | 
| Control group : Time in Therapeutic Range using the venous International Normalized Range monthly monitoring strategy | The Time in Therapeutic Range will be measured as a percentage | Day 0 | 
| Control group : Time in Therapeutic Range using the venous International Normalized Range monthly monitoring strategy | The Time in Therapeutic Range will be measured as a percentage | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interventional group: venous thromboembolic events occurring during the 6-month monitoring period. | In the group being monitored weekly with the CoaguChek INRange® device, the number of venous thromboembolic events occurring during the 6-month monitoring period will be recorded. | Day 0 to Month 6 | 
| Interventional group: haemorrhagic events occurring during the 6-month monitoring period. | In the group being monitored weekly with the CoaguChek INRange® device, the number of haemorrhagic events occurring during the 6-month monitoring period will be recorded. | Day 0 to Month 6 | 
| Control group: venous thromboembolic events occurring with the monthly venous monitoring strategy. | The number of venous thromboembolic events occurring during the 6-month monitoring period will be recorded. | Day 0 to Month 6 | 
| Control group: haemorrhagic events occurring with the monthly venous monitoring strategy. | The number of haemorrhagic events occurring during the 6-month monitoring period will be recorded. | Day 0 to Month 6 | 
| Interventional group : Time in Therapeutic Range using the capillary International Normalized Range weekly monitoring strategy in patients ≤90. |  | Day 0 | 
| Interventional group : Time in Therapeutic Range using the capillary International Normalized Range weekly monitoring strategy in patients ≤90. |  | Month 6 | 
| Interventional group : Time in Therapeutic Range using the capillary International Normalized Range weekly monitoring strategy in patients >90. |  | Day 0 | 
| Interventional group : Time in Therapeutic Range using the capillary International Normalized Range weekly monitoring strategy in patients >90. |  | Month 6 | 
| Control group: Time in Therapeutic Range using the monthly venous monitoring strategy in patients ≤90. |  | Day 0 | 
| Control group: Time in Therapeutic Range using the monthly venous monitoring strategy in patients ≤90. |  | Month 6 | 
| Control group: Time in Therapeutic Range using the monthly venous monitoring strategy in patients >90. |  | Day 0 | 
| Control group: Time in Therapeutic Range using the monthly venous monitoring strategy in patients >90. |  | Month 6 | 
| Interventional group : Cost-consequences study on the weekly INRc monitoring strategy | Cost in terms of hospitalisations (due to haemorrhagic, ischemic and thromboembolic events) using the weekly INRc monitoring strategy will be studied including the cost of the device (equipment and consumables) from the public health insurance's perspective and the nursing time from the point of view of the health care institution. | Month 6 | 
| Interventional group : Budget impact analysis on the weekly INRc monitoring strategy | Estimation of the financial consequences in terms of hospitalisations (due to haemorrhagic, ischemic and thromboembolic events) of adopting the new intervention in France | Year 3 | 
| Control group : Cost-consequences study on the monthly venous monitoring strategy | Cost in terms of hospitalisations (due to haemorrhagic, ischemic and thromboembolic events) using the monthly venous monitoring strategy will be studied from the public health insurance's perspective and the nursing time from the point of view of the health care institution. | Month 6 | 
| Control group : Budget impact analysis on the monthly venous monitoring strategy | An estimation will be made of the financial consequences in terms of hospitalisations (due to haemorrhagic, ischemic and thromboembolic events. | Year 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial Fibrillation, Thrombosis, Stroke, Elderly