Subtherapeutic INR Levels in Patients With AVK: Incidence, Associated Factors, Prognosis and Control Strategies (SULTAN)

A Prospective Observational Study Assessing the Management of Anticoagulation With Vitamin K Antagonists in Patients With Nonvalvular Atrial Fibrillation Treated in Cardiology Practices

This prospective observational study is to assess the predictive factors of poor control of international normalized ratio (INR) to determine the treatment strategies received by patients with a poor control of INR in real-life clinical practice and to explore the effectiveness and safety of these strategies in patients with non-valvular atrial fibrillation who start vitamin K antagonist (VKA) treatment

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Vitamin K Antagonist

• Study Type: Observational
• Enrollment (Actual): 1013

Contacts and Locations

Study Locations

• Spain
  • Multiple Locations, Spain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients diagnosed with non-valvular atrial fibrillation who are going to start vitamine K antagonist treatment or have started over the previous two months and that attend the Cardiology Units at Spanish hospitals (as outpatients).

Description

Inclusion Criteria:

• Patients aged ≥ 18 years.
• Patients with a diagnosis of nonvalvular atrial fibrillation according to the criteria of the Spanish Agency of Medicines and Medical Devices (AEMPS) (2013) who are treated in cardiology practices.
• Patients about to start treatment with a vitamin K antagonist or who are in the first two months of treatment.
• Patients for whom access to at least 80% of INR tests performed during treatment with vitamin K antagonists is expected to be available.
• Patients with the mental and physical capacity to complete the study questionnaires and give their informed consent to participate in the study.

Exclusion Criteria:

• Patients with mitral stenosis or another significant valve disease for which specific treatment is scheduled or has already been performed (prosthesis or valvuloplasty).
• Patients hospitalised at the time of inclusion in the study.
• Patients with a life expectancy of less than 13 months.
• Patients who are participating in a clinical trial.
• Patients receiving double antiplatelet therapy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Cohort 1; Adult patients, diagnosed with no-valvular atrial fibrillation and who have recently initiated or are going to initiate VKA treatment, that attend the Cardiology Units

Drug: Vitamin K Antagonist; The vitamin K antagonists exert their anticoagulant effect through inhibition of the enzyme complex of vitamin K epoxide reductase subunit 1 with subsequent reduction of the gamma-carboxylation of certain glutamic acid molecules endpoints located on factors coagulation II (prothrombin), VII, IX and X and protein C or its cofactor protein S. This gamma-carboxylation has a significant bearing on the interaction of coagulation factors referenced with calcium ions. Without this reaction, blood clotting cannot be initiated. The dose must be adjusted to each patient at baseline and after regular basis, since the sensitivity to anticoagulants varies between individuals and can also vary throughout the treatment. For this, the Prothrombin Time (PT) is used and standardized ratio called International Normalised Ratio (INR).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Normalized Ratio (INR) Time in Therapeutic Range (TTR)	Percentage of time within an INR range of 2-3 estimated using the Rosendaal method	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline thromboembolic risk based on the CHADS2 scale	CHADS2: Cardiac failure, Hypertension, Age, Diabetes, Stroke	Baseline
Baseline thromboembolic risk based on the CHA2DS2-VASc scale	CHA2DS2-VASc:Cardiac failure, Hypertension, Age ≥75, Diabetes, Stroke -Vascular disease, Age and sex category	Baseline
Baseline haemorrhagic risk based on the HAS-BLED scale	HAS-BLED: Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly , Drugs/alcohol	Baseline
Changes in INR time in therapeutic range	INR time in therapeutic range: percentage of time within an INR range of 2-3 estimated using the Rosendaal method	Up to 24 months
Patient preferences with regard to anticoagulant treatment based on patients' questionnaires		Up to 12 months
Satisfaction with the anticoagulant treatment based on the Anti-Clot Treatment Scale (ACTS)		Up to 12 months
Adherence to the anticoagulant treatment: Morisky-Green test		Up to 12 months
Number and type of visits by patients to health professionals related to their anticoagulant treatment		Up to 12 months
Number of patients using anticoagulant treatment strategies	Strategies: patients continuing vitamin K antagonists, patients with changes/adjustments to the dose of vitamin K antagonists and patients whose treatment is changed to direct action oral anticoagulants	Up to 24 months
Number of patients treated according to clinical practice guidelines based on the Spanish Agency of Medicines and Medical Devices (AEMPS) therapeutic positioning report		Up to 24 months
Number of thromboembolic events in patients with inadequate anticoagulation management		Up to 24 months
Number of haemorrhagic events in patients with inadequate anticoagulation management		Up to 24 months

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2015
• Primary Completion (ACTUAL): June 30, 2018
• Study Completion (ACTUAL): March 15, 2019

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (ESTIMATE): November 20, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K
• Other Study ID Numbers: 17943