Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer

NCT ID: NCT02744092

Last Updated: 2023-10-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

811 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-13

Study Completion Date

2021-02-22

Brief Summary

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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.

Detailed Description

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Venous blood clots affect nearly a million Americans each year. Venous clots in the legs are called deep venous thrombosis (DVT) and are dangerous because they travel to the lungs where they cause blockages known as pulmonary emboli (PE). DVT and PE are called venous thromboemboli (VTE). Cancer is a risk factor with nearly 200,000 VTEs in cancer patients each year. The purpose of VTE treatment is to prevent the initial clot from spreading and to prevent new clots from forming. This is accomplished by thinning the blood, or anticoagulation. Without anticoagulation, VTEs recur and are often fatal.

Recently, the FDA has approved 4 new Direct Oral AntiCoagulants (DOACs) for preventing VTE recurrence. Few cancer patients were included in the efficacy trials, and practice guidelines fall silent on whether switching to DOAC therapy is advisable. To fill this knowledge gap, the Alliance Foundation Trials LLC, a research network of academic and community practices across the US, is conducting a pragmatic randomized effectiveness trial.

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 investigators will conduct a trial of 811 cancer patients followed for 6 months. The intervention strategy is DOAC therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is LMWH alone or with warfarin. Within each arm, patients can choose the agent they prefer based on side effects, drug interactions, and practical issues such as co-pays. The trial compares these two strategies in terms of treatment: 1) benefits based on VTE recurrence; 2) harms based on bleeding rates; 3) burdens based on patients' reports of their experiences; and 4) mortality rates.

The investigators hypothesize that the benefits, harms and burdens of DOAC treatment will be non-inferior to, or better than, usual care with LMWH/ warfarin among cancer patients. The information gained will empower cancer patients and physicians to make more informed choices about anticoagulation strategies to manage VTE.

Conditions

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Cancer Venous Thromboembolism Deep Vein Thrombosis (DVT) Pulmonary Embolism (PE) Blood Clot

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Randomized Arm 1 (DOACs)

Randomized 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.

Group Type ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type DRUG

Anticoagulation therapy.

Apixaban

Intervention Type DRUG

Anticoagulation therapy.

Edoxaban

Intervention Type DRUG

Anticoagulation therapy.

Dabigatran

Intervention Type DRUG

Anticoagulation therapy.

Randomized Arm 2 (LMWH)

Randomized 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.

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type DRUG

Anticoagulation therapy.

Dalteparin

Intervention Type DRUG

Anticoagulation therapy.

Enoxaparin

Intervention Type DRUG

Anticoagulation therapy.

Fondaparinux

Intervention Type DRUG

Anticoagulation therapy.

Preference Cohort 1 (DOACs)

If 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).

Group Type ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type DRUG

Anticoagulation therapy.

Apixaban

Intervention Type DRUG

Anticoagulation therapy.

Edoxaban

Intervention Type DRUG

Anticoagulation therapy.

Dabigatran

Intervention Type DRUG

Anticoagulation therapy.

Preference Cohort 2 (LMWH)

If 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.

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type DRUG

Anticoagulation therapy.

Dalteparin

Intervention Type DRUG

Anticoagulation therapy.

Enoxaparin

Intervention Type DRUG

Anticoagulation therapy.

Fondaparinux

Intervention Type DRUG

Anticoagulation therapy.

Interventions

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Rivaroxaban

Anticoagulation therapy.

Intervention Type DRUG

Apixaban

Anticoagulation therapy.

Intervention Type DRUG

Edoxaban

Anticoagulation therapy.

Intervention Type DRUG

Dabigatran

Anticoagulation therapy.

Intervention Type DRUG

Warfarin

Anticoagulation therapy.

Intervention Type DRUG

Dalteparin

Anticoagulation therapy.

Intervention Type DRUG

Enoxaparin

Anticoagulation therapy.

Intervention Type DRUG

Fondaparinux

Anticoagulation therapy.

Intervention Type DRUG

Other Intervention Names

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Xarelto Eliquis Savaysa Pradaxa Coumadin Fragmin Lovenox Arixtra

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

Alliance Foundation Trials, LLC.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Deborah Schrag, MD MPH

Role: STUDY_CHAIR

Alliance Foundation Trials, LLC.

Jean Connors, MD

Role: STUDY_CHAIR

Alliance Foundation Trials, LLC.

Locations

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South County Hematology

Chula Vista, California, United States

Site Status

Sharp Rees-Stealy

Chula Vista, California, United States

Site Status

Washington Hospital Healthcare System

Fremont, California, United States

Site Status

Washington Hospital

Fremont, California, United States

Site Status

VA Central California Fresno Medical Center

Fresno, California, United States

Site Status

Cancer Center Oncology Medical Group

La Mesa, California, United States

Site Status

Medical Oncology Associates- San Diego

San Diego, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

Sharp Rees-Stealy

San Diego, California, United States

Site Status

UCSF Medical Center - Mission Bay

San Francisco, California, United States

Site Status

Saint Joseph's Medical Center

Stockton, California, United States

Site Status

Middlesex Hospital

Middletown, Connecticut, United States

Site Status

The Stamford Hospital

Stamford, Connecticut, United States

Site Status

Morton Plant Hospital

Clearwater, Florida, United States

Site Status

Breast Cancer Center at Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

Memorial Regional Hospital

Hollywood, Florida, United States

Site Status

Hollis Cancer Center

Lakeland, Florida, United States

Site Status

Breast Cancer Center at Memorial Hospital West

Pembroke Pines, Florida, United States

Site Status

Memorial Cancer Institute at Memorial Hospital West

Pembroke Pines, Florida, United States

Site Status

Memorial Hospital West

Pembroke Pines, Florida, United States

Site Status

The Center for Cancer Care-Duluth

Duluth, Georgia, United States

Site Status

Gwinnett Medical Center

Lawrenceville, Georgia, United States

Site Status

The Center for Cancer Care-Snellville

Snellville, Georgia, United States

Site Status

Hawaii Cancer Care POB II

Honolulu, Hawaii, United States

Site Status

Hawaii Oncology Inc POB I

Honolulu, Hawaii, United States

Site Status

Queen's Medical Center

Honolulu, Hawaii, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Hawaii Cancer Care Liliha

Honolulu, Hawaii, United States

Site Status

Hawaii Oncology Inc Kuakini

Honolulu, Hawaii, United States

Site Status

Kootenai Health

Post Falls, Idaho, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

Advocate Illinois Masonic Medical Center

Chicago, Illinois, United States

Site Status

Carle on Vermillion

Danville, Illinois, United States

Site Status

Carle - Effingham

Effingham, Illinois, United States

Site Status

NorthShore University HealthSystem Evanston Hospital

Evanston, Illinois, United States

Site Status

NorthShore University HealthSystem Glenbrook Hospital

Glenview, Illinois, United States

Site Status

NorthShore University HealthSystem Highland Park Hospital

Highland Park, Illinois, United States

Site Status

Carle - Mattoon/Charleston

Mattoon, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

NorthShore University HealthSystem Skokie ACC

Skokie, Illinois, United States

Site Status

The Carle Foundation Hospital/Carle Cancer Center

Urbana, Illinois, United States

Site Status

Franciscan St. Francis Health - Indianapolis

Indianapolis, Indiana, United States

Site Status

Woodland Cancer Care Center

Michigan City, Indiana, United States

Site Status

Franciscan St. Francis Health - Mooresville

Mooresville, Indiana, United States

Site Status

Reid Health

Richmond, Indiana, United States

Site Status

Memorial Hospital at South Bend

South Bend, Indiana, United States

Site Status

Union Hospital

Terre Haute, Indiana, United States

Site Status

Saint Elizabeth Medical Center South

Edgewood, Kentucky, United States

Site Status

Saint Elizabeth Medical Center Fort Thomas

Fort Thomas, Kentucky, United States

Site Status

Chandler Medical Center - University of Kentucky

Lexington, Kentucky, United States

Site Status

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Site Status

Norton Hospital

Louisville, Kentucky, United States

Site Status

University of Louisville Hospital

Louisville, Kentucky, United States

Site Status

University of Louisville Physicians, PSC

Louisville, Kentucky, United States

Site Status

University of Louisville, Division of Surgical Oncology

Louisville, Kentucky, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

DF/BWCC at Milford Regional Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

St. Elizabeth's Medical Center

Brighton, Massachusetts, United States

Site Status

Lowell General Hospital

Lowell, Massachusetts, United States

Site Status

South Shore Hospital

South Weymouth, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Green Bay Oncology, Ltd./St. Francis Hospital

Escanaba, Michigan, United States

Site Status

Masonic Cancer Center University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Health: Clinics and Surgery Center

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Site Status

Siteman Cancer Center - St. Peters

City of Saint Peters, Missouri, United States

Site Status

Veterans Administration/Harry S Truman Memorial Hospital

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center University of Missouri Healthcare

Columbia, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Siteman Cancer Center - South County

St Louis, Missouri, United States

Site Status

Siteman Cancer Center - West County

St Louis, Missouri, United States

Site Status

Community Hospital of Anaconda

Anaconda, Montana, United States

Site Status

Billings Clinic

Billings, Montana, United States

Site Status

Montana Cancer Consortium

Billings, Montana, United States

Site Status

Bozeman Health

Bozeman, Montana, United States

Site Status

Benefis Sletten Cancer Institute

Great Falls, Montana, United States

Site Status

Kalispell Regional Medical Center

Kalispell, Montana, United States

Site Status

Community Medical Center

Missoula, Montana, United States

Site Status

Nevada Cancer Specialists - Oakey

Las Vegas, Nevada, United States

Site Status

Ann M Wierman MD LTD

Las Vegas, Nevada, United States

Site Status

Nevada Cancer Specialists - Tenaya

Las Vegas, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Nevada Cancer Specialists - Fort Apache

Las Vegas, Nevada, United States

Site Status

Comprehensive Cancer Centers of Nevada - Central Valley

Las Vegas, Nevada, United States

Site Status

New Hampshire Oncology - Hematology PA

Concord, New Hampshire, United States

Site Status

New Hampshire Oncology-Hematology PA

Hooksett, New Hampshire, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Dana-Farber/New Hampshire Oncology Hematology

Londonderry, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

SUNY Upstate Medical University

New York, New York, United States

Site Status

Mission Hospital - Memorial Campus

Asheville, North Carolina, United States

Site Status

Southeastern Medical Oncology Center

Clinton, North Carolina, United States

Site Status

Duke University Health System

Durham, North Carolina, United States

Site Status

Southeastern Medical Oncology Center

Goldsboro, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Southeastern Medical Oncology Center

Jacksonville, North Carolina, United States

Site Status

Kenansville Medical Center

Kenansville, North Carolina, United States

Site Status

Kinston Medical Specialists, P.A.

Kinston, North Carolina, United States

Site Status

Lenoir Memorial Hospital

Kinston, North Carolina, United States

Site Status

Onslow Medical Center

Richlands, North Carolina, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

Dayton Physicians LLC, Miami Valley South

Centerville, Ohio, United States

Site Status

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status

Dayton Physicians LLC, Samaritan North

Dayton, Ohio, United States

Site Status

Dayton Clincial Oncology Program

Dayton, Ohio, United States

Site Status

Veteran Affairs Medical Center

Dayton, Ohio, United States

Site Status

Wright Patterson Medical Center

Dayton, Ohio, United States

Site Status

Dayton Physicians LLC, Atrium

Franklin, Ohio, United States

Site Status

Dayton Physicians, Wayne

Greenville, Ohio, United States

Site Status

Greater Dayton Cancer Center

Kettering, Ohio, United States

Site Status

Kettering Medical Center

Kettering, Ohio, United States

Site Status

Toledo Clinic Cancer Center - Maumee

Maumee, Ohio, United States

Site Status

Toledo Clinic Cancer Center - Toledo

Toledo, Ohio, United States

Site Status

Dayton Physicians LLC, Upper valley

Troy, Ohio, United States

Site Status

WellSpan Health Ephrata Cancer Center

Ephrata, Pennsylvania, United States

Site Status

WellSpan Health Adams Cancer Center

Gettysburg, Pennsylvania, United States

Site Status

WellSpan Health Sechler Family Cancer Center

Lebanon, Pennsylvania, United States

Site Status

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

WellSpan Health York Cancer Center

York, Pennsylvania, United States

Site Status

Baylor Scott & White Research Institute

Dallas, Texas, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status

Augusta Health Cancer Center

Fishersville, Virginia, United States

Site Status

Fort Belvoir Community Hospital

Fort Belvoir, Virginia, United States

Site Status

Bon Secours Cancer Institute Medical Oncology at Memorial Regional

Mechanicsville, Virginia, United States

Site Status

Bon Secours Cancer Institute Medical Oncology at St. Francis

Midlothian, Virginia, United States

Site Status

Bon Secours Cancer Institute Medical Oncology at St. Mary's

Richmond, Virginia, United States

Site Status

MultiCare Regional Cancer Center - Auburn

Auburn, Washington, United States

Site Status

MultiCare Regional Cancer Center - Gig Harbor Medical Park

Gig Harbor, Washington, United States

Site Status

MultiCare Regional Cancer Center - Puyallup

Puyallup, Washington, United States

Site Status

Multicare Institute for Research & Innovation

Tacoma, Washington, United States

Site Status

MultiCare Regional Cancer Center - Tacoma

Tacoma, Washington, United States

Site Status

Green Bay Oncology, Ltd./HSHS St. Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

HSHS St. Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

Green Bay Oncology, Ltd./HSHS St. Mary's Hospital Medical Center

Green Bay, Wisconsin, United States

Site Status

HSHS St. Mary's Hospital Medical Center

Green Bay, Wisconsin, United States

Site Status

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Green Bay Oncology, Ltd./HSHS St. Clare Memorial Hospital

Oconto Falls, Wisconsin, United States

Site Status

Green Bay Oncology, Ltd./Door County Memorial Hospital

Sturgeon Bay, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 37266947 (View on PubMed)

Riaz 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.

Reference Type DERIVED
PMID: 34172290 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Study Documents

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Document Type: Study Protocol

Email the study team at [email protected].

View Document

Related Links

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Other Identifiers

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CER-1503-29805

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AFT-28

Identifier Type: -

Identifier Source: org_study_id

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