Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer
CANVAS
2 other identifiers
interventional
811
1 country
151
Brief Summary
The overarching objective of the study is to determine the effectiveness of LMWH/ warfarin vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The intervention strategy is Direct Oral AntiCoagulants (DOAC) therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is low molecular weight heparin (LMWH) alone or with warfarin. The information gained will empower cancer patients and physicians to make more informed choices about anticoagulation strategies to manage VTE.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable cancer
Started Dec 2016
Longer than P75 for not_applicable cancer
151 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 11, 2016
CompletedFirst Posted
Study publicly available on registry
April 20, 2016
CompletedStudy Start
First participant enrolled
December 13, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
February 22, 2021
CompletedResults Posted
Study results publicly available
October 3, 2023
CompletedOctober 3, 2023
February 1, 2023
3.9 years
April 11, 2016
February 10, 2023
September 8, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Cumulative Non-Fatal VTE Recurrence at 6 Months (%)
To compare the effectiveness of anticoagulation with a DOAC (intervention) with LMWH/warfarin (comparator) for preventing VTE recurrence in patients with cancer based on cumulative VTE recurrence reported by patients or clinicians at 6 months. Only VTEs that were nonfatal were considered because of the challenges of attributing cause of death in cancer patients to tumor progression vs. VTE.
6 months
Secondary Outcomes (10)
Cumulative Rates of Major Bleeding
6 months
Health Related Quality of Life Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire
3 months
Burden of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire
3 months
Mortality Reported by Participants' Surrogates (Via Study-specific Questionnaire) or Clinicians (Via Study-specific Case Report Form)
6 months
Health Related Quality of Life Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire
6 months
- +5 more secondary outcomes
Study Arms (4)
Randomized Arm 1 (DOACs)
ACTIVE COMPARATORRandomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.
Randomized Arm 2 (LMWH)
ACTIVE COMPARATORRandomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.
Preference Cohort 1 (DOACs)
ACTIVE COMPARATORIf an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC).
Preference Cohort 2 (LMWH)
ACTIVE COMPARATORIf an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin.
Interventions
Anticoagulation therapy.
Anticoagulation therapy.
Anticoagulation therapy.
Anticoagulation therapy.
Anticoagulation therapy.
Anticoagulation therapy.
Anticoagulation therapy.
Anticoagulation therapy.
Eligibility Criteria
You may qualify if:
- Diagnosis of advanced solid tumor cancer, lymphoma, or myeloma (no time restrictions or limitations) -OR- diagnosis of early stage solid tumor cancer, lymphoma, or myeloma \<= 12 months prior to study enrollment
- Diagnosis of VTE \<= 30 days prior to study enrollment for which potential benefits of anticoagulation therapy to prevent recurrence of VTE are felt by the treating physician to exceed the potential harms
- Any anticoagulation drug/strategy may be used to treat the index VTE; protocol treatment will begin \<= 30days after the index VTE diagnosis date
- Treating physician intends to put participant on anticoagulation therapy for at least three months.
- Age \>= 18 years
- Platelet count is \>= 50,000/mm\^3 (\<= 7 days prior to enrollment)
- CrCl (Creatinine Clearance) is \>= 15 ml/min (\<= 7 days prior to enrollment)
You may not qualify if:
- Diagnosis of acute leukemia
- Has ever received or is scheduled to receive an Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)
- Patients who have ever received an Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) ARE eligible.
- Patients who are scheduled to receive an Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) are NOT eligible
- Ongoing, clinically significant bleeding (CTCAE grade 3 or 4)
- Ongoing therapy with a P-gp inhibitor (e.g., nelfinavir, indinavir, or saquinavir-protease inhibitors for HIV) as these drugs interact with the factor Xa inhibitors
- Therapy with any azole antifungals (e.g., itraconazole, ketaconazole, voriconazole) at the time of enrollment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (151)
South County Hematology
Chula Vista, California, 91911, United States
Sharp Rees-Stealy
Chula Vista, California, 91913, United States
Washington Hospital Healthcare System
Fremont, California, 94538, United States
Washington Hospital
Fremont, California, 94538, United States
VA Central California Fresno Medical Center
Fresno, California, 93073, United States
Cancer Center Oncology Medical Group
La Mesa, California, 91942, United States
Medical Oncology Associates- San Diego
San Diego, California, 92123, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
Sharp Rees-Stealy
San Diego, California, 92123, United States
UCSF Medical Center - Mission Bay
San Francisco, California, 94143, United States
Saint Joseph's Medical Center
Stockton, California, 95204, United States
Middlesex Hospital
Middletown, Connecticut, 06457, United States
The Stamford Hospital
Stamford, Connecticut, 06904, United States
Morton Plant Hospital
Clearwater, Florida, 33756, United States
Breast Cancer Center at Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Hollis Cancer Center
Lakeland, Florida, 33805, United States
Breast Cancer Center at Memorial Hospital West
Pembroke Pines, Florida, 33028, United States
Memorial Cancer Institute at Memorial Hospital West
Pembroke Pines, Florida, 33028, United States
Memorial Hospital West
Pembroke Pines, Florida, 33028, United States
The Center for Cancer Care-Duluth
Duluth, Georgia, 30096, United States
Gwinnett Medical Center
Lawrenceville, Georgia, 30046, United States
The Center for Cancer Care-Snellville
Snellville, Georgia, 30078, United States
Hawaii Cancer Care POB II
Honolulu, Hawaii, 96813, United States
Hawaii Oncology Inc POB I
Honolulu, Hawaii, 96813, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813, United States
Hawaii Cancer Care Liliha
Honolulu, Hawaii, 96817, United States
Hawaii Oncology Inc Kuakini
Honolulu, Hawaii, 96817, United States
Kootenai Health
Post Falls, Idaho, 83854, United States
University of Illinois
Chicago, Illinois, 60612, United States
Advocate Illinois Masonic Medical Center
Chicago, Illinois, 60657, United States
Carle on Vermillion
Danville, Illinois, 61938, United States
Carle - Effingham
Effingham, Illinois, 62401, United States
NorthShore University HealthSystem Evanston Hospital
Evanston, Illinois, 60201, United States
NorthShore University HealthSystem Glenbrook Hospital
Glenview, Illinois, 60026, United States
NorthShore University HealthSystem Highland Park Hospital
Highland Park, Illinois, 60035, United States
Carle - Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
NorthShore University HealthSystem Skokie ACC
Skokie, Illinois, 60076, United States
The Carle Foundation Hospital/Carle Cancer Center
Urbana, Illinois, 61801, United States
Franciscan St. Francis Health - Indianapolis
Indianapolis, Indiana, 46237, United States
Woodland Cancer Care Center
Michigan City, Indiana, 46360, United States
Franciscan St. Francis Health - Mooresville
Mooresville, Indiana, 46158, United States
Reid Health
Richmond, Indiana, 47374, United States
Memorial Hospital at South Bend
South Bend, Indiana, 46601, United States
Union Hospital
Terre Haute, Indiana, 47804, United States
Saint Elizabeth Medical Center South
Edgewood, Kentucky, 41017, United States
Saint Elizabeth Medical Center Fort Thomas
Fort Thomas, Kentucky, 41075, United States
Chandler Medical Center - University of Kentucky
Lexington, Kentucky, 40536, United States
James Graham Brown Cancer Center
Louisville, Kentucky, 40202, United States
Norton Hospital
Louisville, Kentucky, 40202, United States
University of Louisville Hospital
Louisville, Kentucky, 40202, United States
University of Louisville Physicians, PSC
Louisville, Kentucky, 40202, United States
University of Louisville, Division of Surgical Oncology
Louisville, Kentucky, 40202, United States
Eastern Maine Medical Center
Bangor, Maine, 04401, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889, United States
DF/BWCC at Milford Regional Medical Center
Boston, Massachusetts, 01757, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
St. Elizabeth's Medical Center
Brighton, Massachusetts, 02135, United States
Lowell General Hospital
Lowell, Massachusetts, 01854, United States
South Shore Hospital
South Weymouth, Massachusetts, 02190, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Green Bay Oncology, Ltd./St. Francis Hospital
Escanaba, Michigan, 49829, United States
Masonic Cancer Center University of Minnesota Medical Center
Minneapolis, Minnesota, 55455, United States
University of Minnesota Health: Clinics and Surgery Center
Minneapolis, Minnesota, 55455, United States
University of Minnesota Medical Center, Fairview
Minneapolis, Minnesota, 55455, United States
Siteman Cancer Center - St. Peters
City of Saint Peters, Missouri, 63376, United States
Veterans Administration/Harry S Truman Memorial Hospital
Columbia, Missouri, 65201, United States
Ellis Fischel Cancer Center University of Missouri Healthcare
Columbia, Missouri, 65212, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center - South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center - West County
St Louis, Missouri, 63141, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic
Billings, Montana, 59101, United States
Montana Cancer Consortium
Billings, Montana, 59102, United States
Bozeman Health
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Kalispell Regional Medical Center
Kalispell, Montana, 59901, United States
Community Medical Center
Missoula, Montana, 59804, United States
Nevada Cancer Specialists - Oakey
Las Vegas, Nevada, 89102, United States
Ann M Wierman MD LTD
Las Vegas, Nevada, 89128, United States
Nevada Cancer Specialists - Tenaya
Las Vegas, Nevada, 89128, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89148, United States
Nevada Cancer Specialists - Fort Apache
Las Vegas, Nevada, 89148, United States
Comprehensive Cancer Centers of Nevada - Central Valley
Las Vegas, Nevada, 89169, United States
New Hampshire Oncology - Hematology PA
Concord, New Hampshire, 03301, United States
New Hampshire Oncology-Hematology PA
Hooksett, New Hampshire, 03106, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Dana-Farber/New Hampshire Oncology Hematology
Londonderry, New Hampshire, 03053, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
SUNY Upstate Medical University
New York, New York, 13210, United States
Mission Hospital - Memorial Campus
Asheville, North Carolina, 28801, United States
Southeastern Medical Oncology Center
Clinton, North Carolina, 28328, United States
Duke University Health System
Durham, North Carolina, 27710, United States
Southeastern Medical Oncology Center
Goldsboro, North Carolina, 27534, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Southeastern Medical Oncology Center
Jacksonville, North Carolina, 28546, United States
Kenansville Medical Center
Kenansville, North Carolina, 28349, United States
Kinston Medical Specialists, P.A.
Kinston, North Carolina, 28501, United States
Lenoir Memorial Hospital
Kinston, North Carolina, 28501, United States
Onslow Medical Center
Richlands, North Carolina, 28574, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157, United States
Dayton Physicians LLC, Miami Valley South
Centerville, Ohio, 45459, United States
The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210, United States
Dayton Physicians LLC, Samaritan North
Dayton, Ohio, 45415, United States
Dayton Clincial Oncology Program
Dayton, Ohio, 45420, United States
Veteran Affairs Medical Center
Dayton, Ohio, 45428, United States
Wright Patterson Medical Center
Dayton, Ohio, 45433, United States
Dayton Physicians LLC, Atrium
Franklin, Ohio, 45005, United States
Dayton Physicians, Wayne
Greenville, Ohio, 45331, United States
Greater Dayton Cancer Center
Kettering, Ohio, 45409, United States
Kettering Medical Center
Kettering, Ohio, 45429, United States
Toledo Clinic Cancer Center - Maumee
Maumee, Ohio, 43537, United States
Toledo Clinic Cancer Center - Toledo
Toledo, Ohio, 43623, United States
Dayton Physicians LLC, Upper valley
Troy, Ohio, 45373, United States
WellSpan Health Ephrata Cancer Center
Ephrata, Pennsylvania, 17522, United States
WellSpan Health Adams Cancer Center
Gettysburg, Pennsylvania, 17325, United States
WellSpan Health Sechler Family Cancer Center
Lebanon, Pennsylvania, 17042, United States
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224, United States
WellSpan Health York Cancer Center
York, Pennsylvania, 17403, United States
Baylor Scott & White Research Institute
Dallas, Texas, 75204, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
Augusta Health Cancer Center
Fishersville, Virginia, 22939, United States
Fort Belvoir Community Hospital
Fort Belvoir, Virginia, 22060, United States
Bon Secours Cancer Institute Medical Oncology at Memorial Regional
Mechanicsville, Virginia, 23116, United States
Bon Secours Cancer Institute Medical Oncology at St. Francis
Midlothian, Virginia, 23114, United States
Bon Secours Cancer Institute Medical Oncology at St. Mary's
Richmond, Virginia, 23226, United States
MultiCare Regional Cancer Center - Auburn
Auburn, Washington, 98001, United States
MultiCare Regional Cancer Center - Gig Harbor Medical Park
Gig Harbor, Washington, 98335, United States
MultiCare Regional Cancer Center - Puyallup
Puyallup, Washington, 98372, United States
Multicare Institute for Research & Innovation
Tacoma, Washington, 98405, United States
MultiCare Regional Cancer Center - Tacoma
Tacoma, Washington, 98405, United States
Green Bay Oncology, Ltd./HSHS St. Vincent Hospital
Green Bay, Wisconsin, 54301, United States
HSHS St. Vincent Hospital
Green Bay, Wisconsin, 54301, United States
Green Bay Oncology, Ltd./HSHS St. Mary's Hospital Medical Center
Green Bay, Wisconsin, 54303, United States
HSHS St. Mary's Hospital Medical Center
Green Bay, Wisconsin, 54303, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
University of Wisconsin
Madison, Wisconsin, 53792, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Green Bay Oncology, Ltd./HSHS St. Clare Memorial Hospital
Oconto Falls, Wisconsin, 54154, United States
Green Bay Oncology, Ltd./Door County Memorial Hospital
Sturgeon Bay, Wisconsin, 54135, United States
Related Publications (2)
Schrag D, Uno H, Rosovsky R, Rutherford C, Sanfilippo K, Villano JL, Drescher M, Jayaram N, Holmes C, Feldman L, Zattra O, Farrar-Muir H, Cronin C, Basch E, Weiss A, Connors JM; CANVAS Investigators. Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial. JAMA. 2023 Jun 13;329(22):1924-1933. doi: 10.1001/jama.2023.7843.
PMID: 37266947DERIVEDRiaz IB, Fuentes HE, Naqvi SAA, He H, Sipra QR, Tafur AJ, Padranos L, Wysokinski WE, Marshall AL, Vandvik PO, Montori V, Bryce AH, Liu H, Badgett RG, Murad MH, McBane RD 2nd. Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living, Interactive Systematic Review and Network Meta-analysis. Mayo Clin Proc. 2022 Feb;97(2):308-324. doi: 10.1016/j.mayocp.2020.10.041. Epub 2021 Jun 22.
PMID: 34172290DERIVED
Related Links
- FDA Package Insert for Rivaroxaban (Xarelto)
- FDA Package Insert for Apixaban (Eliquis)
- FDA Package Insert for Edoxaban (Savaysa)
- FDA Package Insert for Dabigatran (Pradaxa)
- FDA Package Insert for Dalteparin (Fragmin)
- FDA Package Insert for Enoxaparin (Lovenox)
- FDA Package Insert for Fondaparinux (Arixtra)
- FDA Package Insert for Warfarin (Coumadin)
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This study has several limitations. First, participants and physicians were not blinded to treatment assignment. Second, because participants were randomized within 30 days of a new VTE diagnosis, some were treated with different therapy before randomization. Third, in patients with advanced-stage cancer, it was not possible to distinguish VTE from cancer as the cause of death. Fourth, the included population limits generalizability. Fifth, detailed medication diaries were not obtained.
Results Point of Contact
- Title
- Dr. Jean Connors
- Organization
- Dana-Farber Cancer Institute
Study Officials
- STUDY CHAIR
Deborah Schrag, MD MPH
Alliance Foundation Trials, LLC.
- STUDY CHAIR
Jean Connors, MD
Alliance Foundation Trials, LLC.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 11, 2016
First Posted
April 20, 2016
Study Start
December 13, 2016
Primary Completion
October 31, 2020
Study Completion
February 22, 2021
Last Updated
October 3, 2023
Results First Posted
October 3, 2023
Record last verified: 2023-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- within 6 months of publication of the manuscript, no end date
- Access Criteria
- following a formal request by an investigator to and approval from DFCI
Individual-level de-identified datasets will be made available to investigators working under an institution with a Federal Wide Assurance (FWA) who formally submit a request to the study chairs at the Dana-Farber Cancer Institute. Prior to the release of datasets, DFCI will ensure certain requirements, e.g., IRB approval and data use agreement, are in place. These datasets will be available within 6 months of publication of the manuscript and following a formal request by an investigator to and approval from DFCI.