Assessment of the Effectiveness and Safety Outcome in Patients With Atrial Fibrillation Treated by Apixaban in Belgium (PROVECT)

• ClinicalTrials.gov Identifier: NCT05116267
• Recruitment Status: Withdrawn
• First Posted: November 10, 2021
• Last Update Posted: May 17, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

The PROVECT study is a retrospective, multicentre study assessing the effectiveness and the safety outcomes in patients with non-valvular atrial fibrillation (NVAF) treated by apixaban between 2015 and 2019 (5 years follow up). The study will use harmonized and federated hospital electronic health records (EHRs) from 10 Belgian hospitals. Outcomes of interest are major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality (as an exploratory endpoint, and after confirming the data availability because the death events are not always recorded into hospital EHRs). The study will analyse the outcomes by patient characteristics including the age groups focusing on elderly, thromboembolism risk factors (CHAR2RDSR2R-VASc score), bleeding risk factors (HAS-BLED score), comorbidities (Deyo-Charlson Comorbidity Index, DCCI) score and frailty.

Condition or disease
Atrial Fibrillation

Detailed Description:

Apixaban is an antithrombotic agent that directly inhibits factor Xa, and which has obtained market authorization in the indication "prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA), age ≥75 years, hypertension, diabetes mellitus, and symptomatic heart failure (NYHA ≥ class II)." Among other direct oral anti-coagulants (DOACs) only apixaban has shown a triple beneficial profile (on stroke/systemic embolisms, major bleedings, and all-cause mortality) supported by data from pivotal randomized clinical trials (RCTs). This differentiation has been consistently found in multiple real-world data (RWD) studies including the NAXOS study in France5 and the ARISTOPHANES study in US particularly in terms of incidence of major bleedings for apixaban vs. others DOACs or vitamin K antagonists (VKAs). Although such data can be generalized to different populations, healthcare professionals in Belgium and healthcare authorities have been frequently requesting local scientific data to support the effectiveness and safety outcomes in patients treated by apixaban in local Belgium settings. This scientific data gap is particularly evident for routine care data allowing to understand the apixaban use patterns in the Belgian poly-medicated, frail and new patients starting an apixaban treatment. The PROVECT study aims to address this particular local data gap and its results may help to guide practical clinical decisions .

Study Design

• Study Type: Observational
• Actual Enrollment: 0 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: A Retrospective, Multicenter Study to Assess Effectiveness and Safety Outcome in Patients With Non-valvular Atrial Fibrillation (NVAF) Treated by Apixaban Using Harmonized and Federated Hospital Electronic Health Records (EHRs) in Belgium (PROVECT Study).
• Estimated Study Start Date: October 1, 2021
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2022

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Event Rate of Stroke/Systemic Embolism Requiring Hospitalization: Apixaban treated patients [ Time Frame: Up to 60 months ]
   StroStroke/SE will be identified using hospital EHR which had a stroke/SE diagnosis code as the first listed ICD-10-CM diagnosis code. (Codes list defined) Stroke/SE will be classified into 3 categories: ischemic stroke, hemorrhage stroke, and SE. Time to stroke will be defined as the number of days from the index date to the occurrence of the first stroke/SE requiring hospitalization
2. Event Rate of Major Bleeding Requiring Hospitalization: Apixaban treated patients [ Time Frame: Up to 60 months ]
   Major bleeding will be identified using hospital EHR which had a bleeding diagnosis code as the first listed ICD-10-CM diagnosis or procedure code (Code list defined). Time to major bleeding will be defined as the number of days from the index date to the occurrence of the first major bleeding event requiring hospitalization
3. Event Rate of Gastrointestinal (GI) Bleeding Requiring Hospitalization: Apixaban treated patients [ Time Frame: Up to 60 months ]
   Event rate was defined as number of events divided by 100 participant-years for first occurrence of GI bleeding events after index date was reported. GI bleeding requiring hospitalization was identified using hospital claims which had a GI bleeding ICD code (Code list defined). Index date = the first prescription date of study drugs during intake duration.
4. Event Rate of Intracranial Hemorrhage Requiring Hospitalization: Apixaban treated patients [ Time Frame: Up to 60 months ]
   Event rate was defined as number of events divided by 100 participant-years for first occurrence of intracranial hemorrhage events after index date was reported. Intracranial hemorrhage requiring hospitalization was identified using hospital claims which had an intracranial haemorrhage ICD code (Code list defined) and brain CT or MRI codes. Index date = the first prescription date of study drugs during intake duration
5. Event Rate of Other Bleeding Requiring Hospitalization: Apixaban treated patients [ Time Frame: Up to 60 months ]
   Event rate was defined as number of events divided by 100 participant-years for first occurrence of other bleeding events after index date was reported. Other bleeding requiring hospitalization was identified using hospital claims which had other bleeding ICD code (Code list defined). Index date = the first prescription date of study drugs during intake duration.
6. Mortality rates [ Time Frame: Up to 60 months ]
   Patients who died during a hospitalization during the follow-up period will be labelled by binary indicators.

Secondary Outcome Measures :

1. Rate of discontinuation [ Time Frame: Up to 60 months ]
   Discontinuation is defined as the first day of a period of at least 30 consecutive days (grace period) in which 0 days' supply for the index OAC is detected. Sensitivity analysis with 60-day grace period will be included. The date of discontinuation will be the end date of the last filled prescription before the treatment gap. The mean and median (days) duration of treatment before discontinuation will be calculated.
2. Time-to-discontinuation [ Time Frame: Up to 60 months ]
   Time to discontinuation will be defined as the number of days from the date of index apixaban prescription to the date of discontinuation.
3. Hospital Length of Stay (LOS) [ Time Frame: Up to 60 months ]
   Length of stay will be defined as the number of days a patient received care during an inpatient stay. LOS will be a continuous and categorical variable.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The study is an observational retrospective cohort generated from the Belgian hospitals EHRs. The cohort will consist in anticoagulant (AC)-naive patients (patients that did not receive other oral AC 6 months prior to the apixaban treatment initiation) and AC-experienced patients (patients treated by AC before the inclusion date) diagnosed with non-valvular AF.

The study will cover the period from 01/01/2015 to 31/12/2019 (i.e. maximum of 5 years follow up, noting that all patients will not have this follow up).

Criteria

Inclusion Criteria:

• is 18 years or older at the index date.
• had ≥1 apixaban prescription during the study period from January 1st, 2015 to December 31, 2019.
• had ≥1 medical diagnosis for Atrial Fibrillation, AF (International Classification of Diseases, 10th Revision, Clinical Modification [ICD-10-CM]10 diagnosis codes I48.0, I48.1X, I48.11, I48.19, I48.2X, I48.20, I48.21, I48.9X, I48.91, I49.1) any time before or on index date
• had >1 encounter (visits, prescriptions, etc) within the EHRs.

Exclusion Criteria:

• Medical EHRs indicating a diagnosis code indicative of rheumatic mitral valvular heart disease, mitral valve stenosis (ICD-10-CM diagnosis codes I05.x, I06.x, I07.x, I08.x, I34.x, I35.x, I36.x, I37.x, I38.x, I39.x, I37.x, Q23.x) during the 12-month baseline period,
• Medical EHRs indicating a diagnosis code of VTE (DVT: ICD-10-CM codes: I80.xx, I81.xx, I82.xx, I82.40x, I82.41x, I82.42x, I82.43x, I82.44x, I82.49x, I82.4Yx, I82.4Zx, I82.5xx, I82.51x, I82.52x, I82.53x, I82.54x, I82.55x, I82.56x, I82.59x, I82.5Yx, I82.5Zx, I82.62x, I82.72x, O22.0x, O22.2x, O22.3x; or PE: ICD-10-CM codes I26.01, I26.02, I26.09, I26.90, I26.92, I26.93, I26.94, I26.99) during the 12-month baseline period,
• Medical EHRs indicating a diagnosis (ICD-10-CM) or procedure code (International Classification of Diseases, 10th Revision, Procedure Coding System [ICD-10-PCS]10) of transient AF, or cardiac surgery: Heart valve replacement/transplant: 02YA0Zxx, 02RF0xx, 02RJ0xx, 02RG0xx, 02RH0xx, Z95.2, Z95.3, Z95.4; Pericarditis: I00, I01, I02, I24.1, I30.x, I31.x, I32*coding first the associated cause/etiology; Hyperthyroidism and Thyrotoxicity: E05.0, E05.1, E05.2, E05.3, E05.4, E05.8, E05.9) during the 12-month baseline period;
• Medical EHRs indicating pregnancy during the study period (ICD-10-CM diagnosis codes O00-O9A, Z31, Z32, Z33, Z34, Z36, Z37, Z38, O20-O29, ICD-10 CPS code 109xxx, 10Axxx, 10Dxxx, 10Exxx, 10Hxxx, 10Pxxx, 10Sxxx);
• Medical EHRs indicating diagnosis or procedure for hip/knee replacement surgery within 6 weeks prior to index date (0SR90xx, 0SRA0xx, 0SRB0xx, 0SRC0xx, 0SRD0xx, 0SRE0xx, 0SQ0xx, 0SQB0xx, 0SQB0xx, 0SQB0xx)
• Patients with a prescription for >1 anticoagulants at index date.

Contacts and Locations

Locations

Belgium

Pfizer Site

Brussels, Belgium

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05116267
• Other Study ID Numbers: B0661166; PROVECT Study ( Other Identifier: Alias Study Number )
• First Posted: November 10, 2021
• Last Update Posted: May 17, 2023
• Last Verified: May 2023

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:

Non-valvular atrial fibrillation; Belgium; Apixaban; NVAF

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes