Clinical trial NCT03647254: Efficacy of a Didactic Intervention in Anticoagulated Patients (TAOPE Study)
Official title: Effectivity of a Joint Didactic Intervention by School for Patients on Inappropriate Control Prothrombin Time Anticoagulated Patients. Protocol for Developing a Randomized and Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Health Education
Patient Education as Topic
Blood Coagulation Tests
Keywords: Anticoagulants
Warfarin
Lead sponsor: Andaluz Health Service
Sponsor class: OTHER_GOV
Collaborators: name: Andaluz Health Service
First posted: 2018-08-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Background: Oral anticoagulant drugs represent an essential tool in thrombo-embolic events prevention. Most used are vitamin K antagonists (VKA), which plasma level is monitored measuring prothrombin time using the International Normalized Ratio. If it takes values out of recommended range, the patient will have a higher risk of suffering from thromboembolic or hemorrhagic complications. Previous researches have shown that, at best, only 33% of total patients keep values on therapeutic level.

The investigators intend to improve International Normalized Ratio control figures by a joint didactic intervention based on Junta de Andalucía School for Patients method that will be practiced by anticoagulated patients themselves.

Methods: A randomized clinical trial was carried out at primary care centers from one healthcare area in Malaga (Andalusia, Spain). Study population: patients included on oral anticoagulant therapy program using vitamin K antagonists.

First step: detection of patients on oral anticoagulation program with International Normalized Ratio on therapeutic level during 65% or less over total time. Second step: patients with inappropriate International Normalized Ratio control were practiced a joint didactic intervention "from peer to peer", by a previously trained and expert anticoagulated patient.

Study variables: time on therapeutic levels before and after intervention, sociodemographic variables, vital signs, existence of cardiovascular risk factors, basic blood test, other prescribed drugs, accompanying diseases and social support.

Almost-experimental analytic study with before-after statistical analysis of the intervention. Lineal regression models were applied on main variables results (International Normalized Ratio value, time on therapeutic level) inputting sociodemographic variables, accompanying diseases and social support.

Detailed description: Background and current status:

It has been proved that oral anticoagulant therapy (OAT) is effective in preventing situations with high risk of thromboembolic events and in treating them. It significantly decreases ischemic stroke rates as well as their severity and death risk. However it is a therapy with special features, highlighting: doses and response variability, the close therapeutic range, interactions with other drugs and foods, and potentially severe side effects. This fact compels the investigators to make a close monitoring of those patients.

An important impact in developing cardioembolic or hemorrhagic events due to a inappropriate coagulation control using vitamin K antagonists (VKA), has been described; because of control variations around 15% could result in so relevant clinical problems.

The main OAT indications are deep vein thrombosis, pulmonary embolism, embolic conditions prevention in patients suffering from atrial fibrillation or heart prosthetic valve wearers. Most common embolic event is ictus, which could lead to an important inability and dependence state, what would associate a significant increase in health resources use and costs. Atrial fibrillation (AF) is nowadays the pathology which requires most anticoagulant therapy indications. This fact is partially due to the population aging, since there are both incidence and prevalence increases of this arrhythmia, specially in elderly patients.

Control of patients on OAT were performed in hospitals until a few years ago; nevertheless, changes in social and healthy contexts besides the expansion in this drugs prescribing joined to primary health care qualification and evolution, the development of coagulation handheld measuring devices and the need to improve patients accessibility, had justified the control decentralization and due to this facts, OAT monitoring can be practiced to stable patients on primary care.

When the need of receiving anticoagulation has been stablished, this could be implemented basically using heparin or vitamin-K antagonists or coumadin or new direct action oral anticoagulants as dabigatran, rivaroxaban, apixaban or edoxaban.

The prothrombin time measuring standardization using international normalized ratio (INR) allows the investigators to obtain reliable results in different laboratories. The development of coagulation handheld measuring devices to match INR in capillary blood with high sensitivity and reliability, has made that possible patients on anticoagulant therapy can be controlled on primary care. This allow the investigators a comprehensive approach and control of these patients.

Educational and behavioural interventions could improve VKA anticoagulated patients ability to keep an INR appropriate control using their progresses in knowledge and understanding of the action mechanisms of anticoagulants drugs. A recent research included in Cochrane regarding to those interventions notes that education is particularly important to provide information about safety for patients suffering AF on OAT and let patients to take their own well founded decisions about treatment options and to manage their OAT. However, it could be inferred there are not enough evidences to stablish definite conclusions about educational health interventions impact in INR behaviour in patients suffering from AF on OAT.

In the investigators environment, patients who initiate treatment with VKA are trained at their hematology units until they get a suitable INR level control. After that, patients are followed and evaluated in primary care. The amount of patients with AF on anticoagulation with VKA is high, however, INR levels control results are not ideal.

Therefore, in these three research articles recently conducted in Spain with patients on VKA, it can be observed an inappropriate anticoagulation control.

On the other hand, it should be noted that these chronic patients use to suffer many other conditions and they usually take a lot of medication which makes improve of education aspects aimed at self care and effective health self-management which is absolutely necessary. Selfcare support programs are presented as a tool to accomplish a change in paternalistic method to other one in which citizens could receive more information about their health state (this fact is in accordance with people requests, demonstrated by a rise in the internet consulting about health issues).

"Expert patients" programs, in which instructors are patients with chronic conditions similar to those who receive the training and so they could play a role model, occupying a prominent place inside the selfcare educational initiatives set.

Through the present research the investigators try to show that an organised group educational intervention, conducted by using School for Patients method on VKA anticoagulated patients is able to improve inappropriate INR levels control.

METHODS:

The investigators performed a randomized clinical trial over a period of 12 months.

Study area: one healthcare area in Malaga (Spain) where 741.000 inhabitants from rural or urban population are cared for. It is organized in 33 primary care centers and 19 local doctor´s offices.

Study population: patients on OAT program receiving VKA presenting inappropriate INR levels control and belonging to four primary care centers. Setting the limits and justification of the sample size:

Total population from the health centers which take part in the study amount to approximately 50.000 inhabitants.

Step I: If it is taken into account that prevalence of patients on OAT is about 1.5% of general population, it can be claimed that target population to initiate the study will be 750 anticoagulated patients. It has been observed in previous researches that at least 33% of these patients would not have an appropriate INR level control. In order to reach an accuracy about 4% in the estimate proportion using a normal asymptotic confidence interval with a correction to finite populations on bilaterally 95% and assuming that expected population is about 33% and population total size is 750, it will be necessary to include 311 experimental units in this study.

Step II: If it is accepted an alfa risk of 0.05 and a beta risk of 0.20 in a bilateral contrast between study group and control group, 312 individual will be required (156 in each group) to detect differences equal or higher than 15% between both groups in primary target. It has been estimated a tracking loss rates of 10%. It will be assumed as losts those individual impossible to be located, or those who do not accept to take part or those who do not attend to scheduled revisions, in accordance to the study intervention plan, as well as deceases occurring within six months since the intervention. Given the relevant impact of the development of cardioembolic or hemorrhagic events due to inappropriate INR control, changes about 15% could have great clinical relevance.

Variables. Operative definition The main variable to assess in this study is time on INR therapeutic levels in the last six months receiving VKA treatment. Appropriate INR level control will be assessed in two ways: measuring the therapeutic INR values percentages or Time percentages in therapeutic values estimated using Rosendaal method. It supposes to record the figure of INR value and the date in which the test was carried out. The therapeutic INR values percentages are defined by their acceptable values according to the pathology the patient suffers. It used to be from 2 to 3 if it is about atrial fibrillation or from 2.5 to 3.5 if thromboembolism prevention is carried out after a heart valve surgery has been performed. So, this quantitative variable has to be measured to calculate patients percentage on appropriate range, according to the patient condition.

Independent variables also called study variables are those which could affect to result variable. The investigators are going to classify them in eight groups to make easier their analysis.

Sociodemographic: age and gender. Somatometry and vital signs: Body mass index (BMI), diastolic and systolic blood pressure, and heart rate.

Cardiovascular risk factors: smoking habit, diabetes, arterial hypertension, dyslipidemia and chronic renal failure.

Cardiovascular conditions: atrial fibrillation (AF), interventional cardiac valve diseases with or without AF, ischemic cardiopathy, thromboembolic diseases history (stroke, transient ischemic attack), hemorrhagic stroke, congestive heart failure.

Blood test: Glomerular filtration rates, total cholesterol, HDL and LDL cholesterol and triglycerides. They will be obtained from the last blood test carried out to the patient.

Use of accompanying medication: total number of drugs, anticoagulant type. Consumption of "gastric protector".

Dietary habits: usual consumption of food rich in vitamin K, alcohol consumption.

Data collecting: All variables detailed previously were collected as long as they were suitable in digital medical history or it could be directly obtained from the patient during the medical interview, without the need of changing health center usual clinical practice, over the 6 months prior to the intervention.

First step: patients on OAT program enrolled in several primary health centers belonging to a healthcare area of Málaga were evaluated at the study moment attending to their clinical characteristics. The measurements obtained from the digital clinical history in the last six months before the beginning of the study were recorded, as well as the rest of variables.

Second step: Once the study of the VKA anticoagulation control degree has been performed, patients on inappropriate control were selected. A list of patients with deficient INR control in participant health centers was made. It was considered an inappropriate INR control when the therapeutic INR values percentages was less than 65%, using Rosendaal method to obtain them. In case of no availability, INR control was considered inappropriate when therapeutic INR values percentage resulted less than 60%. In any of the assumptions, the assessment period was at least the last six months.

Eligibility criteria: Inclusion Criteria:

* Patients on VKA treatment for at least the last six months in primary care environment.
* Patients on inappropriate INR level control.
* Patients in whom we have access to, at least, 80% of their INR levels. controls in last six months of treatment with VKA, although they are enrolled in another primary care center.
* Patients who have given written informed consent to take part in the study

Exclusion Criteria:

* Patients suffering from cognitive impairment wich prevents understanding what was written in the information sheet and informed consent.
* Limited mobility patients, terminal patients, alcoholism or drug addiction, severe psychiatric illness or any other reason which makes patients to be present at center´s meetings imposible.

Primary outcomes:
measure: Time on INR therapeutic levels in the last six months receiving VKA treatment
timeFrame: Six months
Secondary outcomes:
measure: Sociodemographic
timeFrame: Six months
measure: Body mass index (BMI)
timeFrame: 0 and 12 months.
measure: Diastolic and systolic blood pressure
timeFrame: 0 and 12 months.
measure: Heart rate
timeFrame: 0 and 12 months.
measure: Smoking habit
timeFrame: 0 and 12 months.
measure: diabetes
timeFrame: 0 and 12 months.
measure: Arterial hypertension
timeFrame: 0 and 12 months.
measure: Dyslipidemia
timeFrame: 0 and 12 months.
measure: Chronic renal failure
timeFrame: 0 and 12 months.
measure: Atrial fibrillation
timeFrame: 0 and 12 months.
measure: Interventional cardiac valve diseases with or without atrial fibrillation
timeFrame: 0 and 12 months.
measure: Ischemic cardiopathy
timeFrame: 0 and 12 months.
measure: Thromboembolic diseases history (stroke, transient ischemic attack)
timeFrame: 0 and 12 months.
measure: Hemorrhagic stroke
timeFrame: 0 and 12 months.
measure: Congestive heart failure
timeFrame: 0 and 12 months.
measure: Glomerular filtration rates
timeFrame: 0 and 12 months.
measure: Total cholesterol
timeFrame: 0 and 12 months.
measure: HDL Cholesterol
timeFrame: 0 and 12 months.
measure: LDL cholesterol
timeFrame: 0 and 12 months.
measure: Triglycerides
timeFrame: 0 and 12 months.
measure: Total number of drugs
timeFrame: 0 and 12 months.
measure: Anticoagulant type
timeFrame: 0 and 12 months.
measure: Consumption of "gastric protector"
timeFrame: 0 and 12 months.
measure: Usual consumption of food rich in vitamin K
timeFrame: 0 and 12 months.
measure: Alcohol consumption
timeFrame: 0 and 12 months.
Other outcomes:
Locations:
city: Málaga
country: Spain
facility: Distrito Sanitario Málaga. Servicio Andaluz de Salud
Study officials:
affiliation: Servicio de salud pública de Andalucía. Málaga, España
name: Francisco J Navarro Moya, Enfermera
role: STUDY_CHAIR
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