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

Completed

• Conditions: Venous Thromboembolism
• Interventions: Drug: Parenteral anticoagulant; Drug: Warfarin; Drug: Apixaban; Drug: Rivaroxaban; Drug: Dabigatran; Drug: Edoxaban

• Registration Number: NCT05022563
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-20
• Study First Submitted QC: 2021-08-20
• Study First Posted: 2021-08-26
• Study Start: 2021-08-31
• Primary Completion: 2021-09-30
• Study Completion: 2021-09-30
• Status Verified: 2022-09
• Results First Submitted: 2022-09-15
• Results First Submitted QC: 2022-09-15
• Last Update Submitted: 2022-09-15
• Results First Posted: 2023-08-03
• Last Update Posted: 2023-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55759

Inclusion Criteria

1. Incident VTE diagnosis in an inpatient or outpatient setting between 1 Mar 2013 and 30 Jun 2019
2. 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)
3. Aged ≥18 years at index date

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Parenteral anticoagulant only	Parenteral anticoagulant	LMWH, UFH
Warfarin-based	Warfarin	Warfarin only + parenteral anticoagulant bridged warfarin
NOAC-based	Apixaban	NOAC only + parenteral anticoagulant bridged NOAC NOAC: apixaban, rivaroxaban, dabigatran, edoxaban
NOAC-based	Edoxaban	NOAC only + parenteral anticoagulant bridged NOAC NOAC: apixaban, rivaroxaban, dabigatran, edoxaban
NOAC-based	Rivaroxaban	NOAC only + parenteral anticoagulant bridged NOAC NOAC: apixaban, rivaroxaban, dabigatran, edoxaban
NOAC-based	Dabigatran	NOAC only + parenteral anticoagulant bridged NOAC NOAC: apixaban, rivaroxaban, dabigatran, edoxaban

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Were Persistent on Index Anticoagulant Treatment for 6 Months	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)	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.
Number of Participants With Interruption in Index Anticoagulant Treatment	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)	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.
Time to Treatment Switch	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)	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.
Overall Index Anticoagulant Treatment Duration	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)	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.
Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Kidney Function Change	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)	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.
Time to Treatment Interruption	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)	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.
Number of Participants Who Switched to Another Anticoagulant Therapy	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)	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.
Number of Participants With Clinical Events Preceding Index Anticoagulant Treatment Interruption	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)	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.
Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Major Bleeding	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)	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.
Time to Treatment Discontinuation	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)	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.
Number of Participants Who Were Persistent on Index Anticoagulant Treatment for 3 Months	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)	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.
Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Complications of VTE	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)	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.
Number of Participants Who Completely Discontinued Index Anticoagulant Treatment	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)	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.
Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Thromboembolism	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)	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.
Number of Participants With Clinical Events Preceding Index Anticoagulant Treatment Discontinuation	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)	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.
Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Major Surgery	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)	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.
Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Cancer-related Event	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)	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.
Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Liver Function Change	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)	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.

Trial Locations

Locations (2)

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Sungkyunkwan University; 🇰🇷 Suwon-si, Korea, Republic of