Treatment Patterns and Bleeding Risk of Anticoagulants in Patients With Venous Thromboembolism in Korea

NCT05022563 | Completed Results FDA Drug

• 2 other identifiers: X9001305VTE HIRA Study
• Study Type: observational
• Target: 55,759
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a retrospective, observational, nationwide population-based cohort study utilizing the South Korea's Health Insurance and Review Assessment Service (HIRA) database. The aims of this study are to describe the sociodemographic and clinical characteristics of patients with venous thromboembolism according to their anticoagulant treatment (parenteral anticoagulants, warfarin, or non-vitamin K antagonist oral anticoagulants), to describe the treatment patterns related to anticoagulants, and to examine the risk of major bleeding according to the specific type of oral anticoagulants. The study will be conducted in two phases: Phase I for descriptive study and Phase II for comparative study.

Conditions

Venous Thromboembolism

Keywords

Venous thromboembolism; anticoagulant; treatment pattern; bleed

Outcome Measures

Primary Outcomes (18)

• Number of Participants With Interruption in Index Anticoagulant Treatment

  Treatment interruption was defined as when a participant had a gap with no new treatment within 30 days of the estimated end of supply of index treatment, but subsequently restarted the index treatment after this period of 30 days. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event.

  From index date up to treatment interruption, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Time to Treatment Interruption

  Treatment interruption was defined as when a participant had a gap with no new treatment within 30 days of the estimated end of supply of index treatment, but subsequently restarted the index treatment after this period of 30 days. The time to treatment interruption was defined as the period from the index date to the date of treatment interruption. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event.

  From index date up to treatment interruption, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants Who Switched to Another Anticoagulant Therapy

  Treatment switching was defined as a prescription of another anticoagulant therapy that was started after the treatment initiation of the index anticoagulant treatment and within 30 days after the estimated end of supply of the index anticoagulant drug (exposure to the new anticoagulant treatment must last for at least 30 days to be considered as a treatment switch). The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event.

  From index date up to treatment switch, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Time to Treatment Switch

  Treatment switching was defined as a prescription of another anticoagulant therapy that was started after the treatment initiation of the index anticoagulant treatment and within 30 days after the estimated end of supply of the index anticoagulant drug (exposure to the new anticoagulant treatment must last for at least 30 days to be considered as a treatment switch). The time to treatment switch was defined as the period from the index date to the date of treatment switch. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event.

  From index date up to treatment switch, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants Who Completely Discontinued Index Anticoagulant Treatment

  Treatment discontinuation (complete discontinuation; no reinitiation) was defined as when a participant who ended their first continuous treatment episode with the index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event.

  From index date up to treatment discontinuation, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Time to Treatment Discontinuation

  Treatment discontinuation (complete discontinuation; no reinitiation) was defined as when a participant who ended their first continuous treatment episode with the index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. The time to treatment discontinuation was defined as the period from the index date to the date of treatment discontinuation. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event.

  From index date up to treatment discontinuation, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Overall Index Anticoagulant Treatment Duration

  Overall anticoagulant treatment duration was defined as the time period from the index date to the earliest of treatment interruption, switch, or discontinuation. Treatment interruption: when a participant had a gap with no new treatment within 30 days of estimated end of supply of index treatment, but subsequently restarted index treatment after this period of 30 days. Treatment switching: a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Treatment discontinuation: when a participant who ended their first continuous treatment episode with index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event.

  From index date up to the earliest of treatment interruption, switch, or discontinuation; during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants Who Were Persistent on Index Anticoagulant Treatment for 3 Months

  Participants were considered to be persistent on index anticoagulant treatment if a participant had evidence of a repeat prescription within 30 days of the end of their prescription and does not experience any of the events that included treatment interruption (participant had a gap with no new treatment within 30 days of estimated end of supply of index treatment, but subsequently restarted index treatment after 30 days), switch (prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug), or discontinuation (participant ended their first continuous treatment episode with index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time). Index date: date of first prescription for anticoagulants within 30 days after the index VTE event.

  Within 3 months of index date, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants Who Were Persistent on Index Anticoagulant Treatment for 6 Months

  Participants were considered to be persistent on index anticoagulant treatment if a participant had evidence of a repeat prescription within 30 days of the end of their prescription and does not experience any of the events that included treatment interruption (participant had a gap with no new treatment within 30 days of estimated end of supply of index treatment, but subsequently restarted index treatment after 30 days), switch (prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug), or discontinuation (participant ended their first continuous treatment episode with index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time). Index date: date of first prescription for anticoagulants within 30 days after the index VTE event.

  Within 6 months of index date, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Index Anticoagulant Treatment Interruption

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment interruption. Treatment interruption was defined as when a participant had a gap with no new treatment within 30 days of the estimated end of supply of index treatment, but subsequently restarted the index treatment after this period of 30 days. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event.

  Within 30 days before treatment interruption during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Major Bleeding

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event "major bleeding" are reported.

  Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Complications of VTE

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event "complications of VTE" are reported.

  Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Thromboembolism

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event "thromboembolism" are reported.

  Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Major Surgery

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event "major surgery" are reported.

  Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Cancer-related Event

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event "cancer-related event" are reported among participants without active cancer. Data not collected and reported for participants with active because all participants already had cancer.

  Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Kidney Function Change

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event "kidney function change" are reported.

  Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Liver Function Change

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event "liver function change" are reported.

  Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

• Number of Participants With Clinical Events Preceding Index Anticoagulant Treatment Discontinuation

  Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment discontinuation. Treatment discontinuation (complete discontinuation; no reinitiation) was defined as when a participant who ended their first continuous treatment episode with the index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event.

  Within 30 days before treatment discontinuation during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study)

Study Arms (3)

Parenteral anticoagulant only

LMWH, UFH

Drug: Parenteral anticoagulant

Warfarin-based

Warfarin only + parenteral anticoagulant bridged warfarin

Drug: Warfarin

NOAC-based

NOAC only + parenteral anticoagulant bridged NOAC NOAC: apixaban, rivaroxaban, dabigatran, edoxaban

Drug: Apixaban; Drug: Rivaroxaban; Drug: Dabigatran; Drug: Edoxaban

Interventions

Parenteral anticoagulant DRUG

Parenteral anticoagulant only

Parenteral anticoagulant only

Warfarin DRUG

Warfarin-based

Warfarin-based

Apixaban DRUG

Apixaban

NOAC-based

Rivaroxaban DRUG

Rivaroxaban

NOAC-based

Dabigatran DRUG

Dabigatran

NOAC-based

Edoxaban DRUG

Edoxaban

NOAC-based

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients diagnosed with venous thromboembolism from the South Korea's Health Insurance Review and Assessment Service (HIRA) database between Mar 1, 2013 and Jun 30, 2019

You may qualify if:

• Incident VTE diagnosis in an inpatient or outpatient setting between 1 Mar 2013 and 30 Jun 2019
• Received anticoagulation therapy (all medication codes for anticoagulants approved for VTE in Korea; UFH, LMWH, warfarin, and NOACs) within 30 days of their VTE diagnosis (the index date will be defined as the date of treatment initiation with anticoagulants)
• Aged ≥18 years at index date

You may not qualify if:

• Had a record of VTE diagnosis within the 12-month period prior to the index VTE encounter.
• Diagnosed with atrial fibrillation/flutter, mechanical heart valve replacement or mitral stenosis anytime prior to index date
• Had a record of Inferior Vena Cava filter anytime prior to index date
• Received anticoagulatory therapy within the 12-month period prior to index VTE encounter
• Prescribed two different anticoagulants on the same index date
• Had a record of pregnancy within the 9-month period prior to index date
• Had a record of active cancer within the past 6 months of period prior to index date

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Sungkyunkwan University

Suwon, South Korea

Location

Related Links

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

MeSH Terms

Conditions

Venous Thromboembolism; Hemorrhage

Interventions

Warfarin; apixaban; Rivaroxaban; Dabigatran; edoxaban

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Pyridines; Benzimidazoles

Limitations and Caveats

Phase 2 was not conducted due to insufficient statistical power that would lead to small and imbalanced sample sizes in comparison groups.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 26, 2021
• Study Start: August 31, 2021
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: August 3, 2023
• Results First Posted: August 3, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)