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Apixaban Drug Utilization Study In Stroke Prevention In Atrial Fibrillation (Spaf) (SPAF)

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ClinicalTrials.gov Identifier: NCT03441633
Recruitment Status : Completed
First Posted : February 21, 2018
Results First Posted : April 19, 2019
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
Apixaban is a direct anticoagulant, which inhibits the factor Xa. Its clinical efficiency in prevention of stroke and systemic embolism in adult patients with NVAF (non/valvular atrial fibrillation) was demonstrated as well as has shown better safety profile compared with warfarin. A Drug Utilization study will evaluate whether this drug has been used in accordance with the approved indication and recommendations described in the summary of product characteristics (SmPC) and estimate possible misuse or overuse apixaban.

Condition or disease Intervention/treatment
Atrial Fibrillation Drug: apixaban Drug: dabigatran Drug: VKA Drug: rivaroxaban

Detailed Description:

The primary research question is to evaluate the apixaban utilization according to the approved SPAF indication and recommendations by EMA.

In addition a comparison with a cohort of NVAF patients treated with VKA, dabigatran and rivaroxaban for the SPAF indication will also be performed.

Objective 1: To characterize patients using apixaban according to demographics, comorbidity, risk of thromboembolic events (CHADS2 and CHA2DS2-Vasc scores), risk of bleeding events (HAS-BLED score), comedications and compare it with the profile of patients treated with VKA, dabigatran and rivaroxaban.

Objective 2: Describe the level of appropriate usage according to the posology recommended in the apixaban SmPC.

Objective 3: Describe the potential interactions with other drugs prescribed concomintatly according with the SmPC recommendations.

Objective 4: Estimate the level of apixaban adherence by the medication possession ratio (MPR) and discontinuation rates and compare it with VKA, dabigatran and rivaroxaban cohort.

Objective 5: To analyze INR (International Normalized Ratio) values during the last 12 months and to obtain TTR (Time in Therapeutic Range) values in patients previously treated with VKA, and during the whole study period for those in the cohort treated with VKA.


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Study Type : Observational
Actual Enrollment : 51690 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: APIXABAN DRUG UTILIZATION STUDY IN STROKE PREVENTION IN ATRIAL FIBRILLATION (SPAF)
Actual Study Start Date : February 18, 2016
Actual Primary Completion Date : March 8, 2017
Actual Study Completion Date : March 8, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Apixaban

Group/Cohort Intervention/treatment
Group 1. Apixaban

Patients who are on treatment with apixaban.

1a. patients who have initiated with apixaban as treatment naïve (no prior prescription of VKA previous to the 12 months before index date).

1b. patients who previously have been treated with VKA in the 12 months before index date.

Drug: apixaban
current or new medication

Group 2. VKA

Patients who are on treatment with VKA.

2a. patients who have initiated with VKA as treatment naïve (no prior prescription of VKA previous to the 12 months before index date).

2b. patients who previously have been treated with VKA in the 12 months before index date.

Drug: VKA
current or new medication

Group 3. Dabigatran

Patients who are on treatment with dabigatran.

3a. patients who have initiated with dabigatran as treatment naïve (no prior prescription of VKA previous to the 12 months before index date).

3b. patients who previously have been treated with VKA in the 12 months before index date.

Drug: dabigatran
current or new medication

Group 4. Rivaroxaban

Patients who are on treatment with rivaroxaban.

4a. patients who have initiated with rivaroxaban as treatment naïve (no prior prescription of VKA previous to the 12 months before index date).

4b. patients who previously have been treated with VKA in the 12 months before index date.

Drug: rivaroxaban
current or new medication




Primary Outcome Measures :
  1. Number of Participants by Their Sociodemographic Characteristics: Smoking Habit [ Time Frame: Day 1 ]
    Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included smoking habit.

  2. Number of Participants by Their Sociodemographic Characteristics: Alcoholic Habit [ Time Frame: Day 1 ]
    Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included alcoholic habit.

  3. Number of Participants by Their Sociodemographic Characteristics: MEDEA [ Time Frame: Day 1 ]
    Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included MEDEA. MEDEA was a deprivation index that was associated with overall mortality in urban areas. It included factors like job, education, housing conditions and single parent homes. The MEDEA index was categorized in quintiles for urban areas, with quintile 1 corresponding to the least deprived population and quintile 5, the most deprived.

  4. Number of Participants by Their Sociodemographic Characteristics: Body Mass Index (BMI) [ Time Frame: Day 1 ]
    Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included BMI. BMI was defined as an index for assessing overweight and underweight and was obtained by dividing body weight in kilograms (kg) by height in meters squared (m^2).

  5. Number of Participants by Comorbidity [ Time Frame: Up to 12 months after date of first prescription ]
    Comorbidity was defined as the presence of one or more additional diseases or disorders co-occurring with (that is, concomitant or concurrent with) a primary disease or disorder.

  6. Risk of Bleeding Events: HAS-BLED Score [ Time Frame: Up to 12 months prior to enrollment ]
    Risk of bleeding events was assessed by using HAS-BLED score. HAS-BLED was a scoring system that was developed to assess 1 year risk of occurrence of major hemorrhage. HAS-BLED score was assessed by combining score of 9 risk factors: hypertension history, renal disease, liver disease, stroke history, prior major bleeding or predisposition to bleeding, labile international normalized ratio (INR), age >65 years, medication usage predisposing to bleeding and alcohol or drug usage history. The total score ranged from 0 to 9 where 0 = low risk of bleed per 100 participants-year and >3 = high risk of bleed per 100 participants-year.

  7. Risk of Thromboembolic Events: CHADS2 Score [ Time Frame: Up to 12 months prior to enrollment ]
    Thromboembolic events were defined as an embolic stroke that occurred when a blood clot that formed elsewhere in the body breaks loose and travels to the brain via bloodstream. Risk of thromboembolic events was calculated using CHADS2 score. CHADS2 score was assessed by combining score of 5 risk factors (congestive heart failure history, hypertension history, age >=75 years, diabetes mellitus history and stroke/transient ischemic attack symptoms previously). Total CHADS2 score ranged from 0-6 where 0 =low risk and 6 =high risk of stroke.

  8. Risk of Thromboembolic Events: CHA2DS2Vasc Score [ Time Frame: Up to 12 months prior to enrollment ]
    Thromboembolic events were defined as an embolic stroke that occurred when a blood clot that formed elsewhere in the body breaks loose and travels to the brain via bloodstream. Risk of thromboembolic events was calculated using CHA2DS2Vasc score. CHA2DS2Vasc score was assessed by combining score of 8 risk factors (female, >=65 and <75 years, congestive heart failure history, hypertension history, diabetes mellitus history, vascular disease history, age >=75 years and stroke/TIA symptoms previously). Total CHA2DS2Vasc score ranged from 0-9 where 0=low risk and 9=high risk of stroke.

  9. Number of Participants by Comedications [ Time Frame: Up to 30 days after date of first prescription ]
    Comedication was defined as the second or alternative medication used to relieve the side-effects of another medicine.

  10. Number of Participants With Apixaban Adherence With VKA, Dabigatran and Rivaroxaban as Assessed by Medication Possession Ratio (MPR) [ Time Frame: Up to 12 months after date of first prescription ]
    MPR was one of the methods of measuring adherence and was defined as the ratio of all days supply to elapsed days, during the 12-month observation period. All days supply defined as sum of number of days supply between the start date and last prescription dispensed. Elapsed days defined as number of days between the start date and the last prescription dispensed. There were three categories of adherence: poor defined as <80% of MPR, good defined as between 80% and 120% of MPR and over adherence defined as >120% of MPR.

  11. Number of Participants With Apixaban Adherence With VKA, Dabigatran and Rivaroxaban as Assessed by Discontinuation Throughout the Year [ Time Frame: Up to 12 months after date of first prescription ]
    Discontinuation rate was defined as the lack of subsequent prescription of the index drugs within 2 months after last supply day of the last prescription. It was analyzed by calculating the treatment withdrawal or switch rate.

  12. Apixaban Adherence With VKA, Dabigatran and Rivaroxaban by Number of Defined Daily Dose (NDDD) [ Time Frame: Up to 12 months after date of first prescription ]
    NDDD was a measure that represented the average daily maintenance dose for the main indication of a drug.

  13. International Normalized Ratio (INR) Values During the Last 12 Months Values in Participants Previously Treated With VKA [ Time Frame: Up to 12 months after date of first prescription ]
    INR was defined as the ratio of the participant's prothrombin time and the normal mean prothrombin time. Prothrombin time defined as a time taken by the blood to clot in participants receiving oral anticoagulant medication. INR was categorized according to the risk level: risk for coagulation (INR<2); optimal range (2<INR<3); and risk of hemorrhages (INR>3).

  14. Time in Therapeutic Range (TTR) Values During the Last 12 Months Values in Participants Previously Treated With VKA [ Time Frame: Up to 12 months after date of first prescription ]
    TTR was defined as the duration of time in which the participant's INR values were within a desired range (2 to 3). INR was defined as the ratio of the participant's prothrombin time and the normal mean prothrombin time. Prothrombin time defined as a time taken by the blood to clot in participants receiving oral anticoagulant medication. INR was categorized according to the risk level: risk for coagulation (INR<2); optimal range (2<INR<3); and risk of hemorrhages (INR>3).



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

SIDIAP currently collects information from 274 primary health care centers, including more than 5.8 million patients, about 80 % of the Catalonia population, or more than 10 % of the Spanish population covered by the Catalan Institute of Health.

The study population for these cohorts includes all eligible subjects from the source population with a first -recorded prescription of apixaban VKA, dabigatran or rivaroxaban for the SPAF indication, registered in SIDIAP database and diagnosis of NVAF for study period.

Criteria

Inclusion Criteria:

  1. Patients more than 18 years-old.
  2. Patients diagnosed with NVAF registered in primary care according to ICD-10.
  3. Patients initiating apixaban (naïve or VKA experienced), VKA (naïve or VKA experienced), dabigatran or rivaroxaban for the SPAF indication.
  4. Continuous enrolment in the 12 months pre-index.

Exclusion Criteria:

  1. Patients with valvular heart disease (ICD 10: I05.0-I05.09, I08.0-I08.9) including patients with mitral prosthetic valves.
  2. Lost to follow-up (e.g. transfer to primary care center non-ICS).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03441633


Locations
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Spain
IDIAP Jordi Gol
Barcelona, Cataluña, Spain, 8007
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03441633     History of Changes
Other Study ID Numbers: B0661076
SPAF ( Other Identifier: Alias Study Number )
First Posted: February 21, 2018    Key Record Dates
Results First Posted: April 19, 2019
Last Update Posted: April 19, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Keywords provided by Pfizer:
atrial fibrillation
apixaban
stroke
Additional relevant MeSH terms:
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Atrial Fibrillation
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Rivaroxaban
Apixaban
Dabigatran
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants