Anticoagulation Length of ThErapy and Risk of New Adverse evenTs In Venous thromboEmbolism Study (ALTERNATIVE)

The Comparative Effectiveness of Warfarin and New Oral Anticoagulants for the Extended Treatment of Venous Thromboembolism

The proposed research seeks to provide insights on the contemporary epidemiology, treatment, and outcomes of VTE, including examining the uptake of new treatment strategies, the efficacy and safety of different anticoagulant options, and the impact of venous thromboembolism on patient-defined outcomes, such as quality-of-life, symptom burden, and treatment satisfaction. This information is crucial to helping clinicians and patients choose between various treatment options for venous thromboembolism in order to achieve the best possible balance between the risks, benefits, and impact on health.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism; Anticoagulants and Bleeding Disorders
• Intervention / Treatment: Drug: Oral Anticoagulant

Detailed Description

Venous thromboembolism (VTE) is a leading cause of cardiovascular death and continues to be a major public health issue in the United States. The cornerstone of current VTE treatment is anticoagulation, typically given for ≥ 3 months during the acute phase of thrombosis. Afterwards, extended-duration anticoagulation can be considered for selected higher-risk patients. Treatment options for VTE have expanded substantially in recent years, most notably through the availability of direct oral anticoagulants (DOACs). Yet there are many remaining gaps in the understanding of how to manage VTE to maximize net clinical benefit.

The long-range objective of this project is to reduce the morbidity and mortality associated with VTE in adults and evaluate contemporary treatment patterns and long-term outcomes after VTE. This initial phase of the study will assemble an observational cohort of adults with VTE diagnosed between 2010-2018. Study subjects will be identified from two integrated healthcare delivery systems (Kaiser Permanente Northern California and Kaiser Permanente Southern California) and followed until December, 2019. Data will be obtained from administrative and electronic health records, supplemented with a cross-sectional patient survey.

The first two aims will be to compare the rates of recurrent VTE and hemorrhage between (1) extended anticoagulation vs. no extended anticoagulation after VTE; and (2) DOAC vs. warfarin treatment of VTE. The third specific aim is to describe patient-defined outcomes in adults with VTE in the current treatment era. This will be accomplished by surveying subjects with VTE to collect data on generic and disease-specific quality-of-life as well as on anticoagulant treatment satisfaction. Combining clinical, outcome, and survey data with administrative data will create a contemporary cohort of VTE patients that can serve as a rich source of information for use in facilitating comparative effectiveness research addressing optimal VTE management within real-world practice settings.

• Study Type: Observational
• Enrollment (Actual): 39603

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Kaiser Permanente Northern California
    • Pasadena, California, United States, 91101
      • Kaiser Permanente Southern California

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

The source populations for the study will be adults diagnosed with acute venous thromboembolism who were enrolled in Kaiser Permanente Northern California or Kaiser Permanente Southern California, two large, integrated healthcare delivery systems in California.

Description

Inclusion Criteria:

• Adults (age ≥ 18 years) enrolled in Kaiser Permanente Northern California or Kaiser Permanente Southern California
• Index VTE event, defined as an incident clinical encounter (inpatient, emergency department, or outpatient) with a primary or secondary diagnosis of VTE during the time period January 1, 2010 to December 31, 2018
• Anticoagulant prescription (oral or parenteral) filled after index VTE discharge/encounter date
• Continuous outpatient anticoagulant therapy for ≥ 3 months from fill date of prescription
• Continuous pharmacy benefits and health plan membership for at least 12 months before the index VTE event date

Exclusion Criteria:

- Incomplete information on age and sex

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Extended anticoagulation; Patients with acute VTE treated with oral anticoagulants for > 3 months	Drug: Oral Anticoagulant; Oral anticoagulants used to treat or prevent venous thromboembolism; Other Names: warfarin, dabigatran, rivaroxaban, apixaban, edoxaban
No extended anticoagulation; Patients with acute VTE treated with oral anticoagulants for no longer than 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent venous thromboembolism	Recurrent VTE will be defined as a new VTE encounter that is occurs after the index VTE event date. The encounter must represent a new diagnosis or symptomatology that is attributable to VTE.	From the index VTE date until death, disenrollment from the health system, or the end of the planned outcome assessment (December 31, 2019)
Hospitalization for hemorrhage	Hospitalization for extracranial or intracranial hemorrhage	From the index VTE date until death, disenrollment from the health system, or the end of the planned outcome assessment (December 31, 2019)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	All-cause death	From the index VTE date until disenrollment from the health system or the end of the planned outcome assessment (December 31, 2019)
Health-related quality of life	Generic health-related quality of life, measured according to the 36 item Short Form Survey	years 2018 and 2019
Anticoagulant treatment satisfaction	Anti-Clot Treatment Satisfaction Scale	years 2018 and 2019

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Patient-Centered Outcomes Research Institute; Kaiser Permanente
• Investigators: Principal Investigator: Margaret C. Fang, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2010
• Primary Completion (ACTUAL): December 31, 2019
• Study Completion (ACTUAL): June 21, 2022

Study Registration Dates

• First Submitted: September 20, 2017
• First Submitted That Met QC Criteria: September 20, 2017
• First Posted (ACTUAL): September 25, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Embolism and Thrombosis; Hemostatic Disorders; Blood Coagulation Disorders; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Rivaroxaban; Dabigatran; Apixaban; Edoxaban; Warfarin; Anticoagulants
• Other Study ID Numbers: NOACs-1510-32651

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No