Summary

Location
at San Diego, California and other locations
Dates
study started
completion around
Principal Investigator
by Annette Von Drygalski, MD

Description

Summary

In parallel with the growth of American Thrombosis and Hemostasis Network's (ATHN) clinical studies, the number of new therapies for all congenital and acquired hematologic conditions, not just those for bleeding and clotting disorders, is increasing significantly. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have yet to demonstrate long-term safety and effectiveness beyond the pivotal trials that led to their approval. In addition, results from well-controlled, pivotal studies often cannot be replicated once a therapy has been approved for general use.(1,2,3,4) In 2019 alone, the United States Food and Drug Administration (FDA) has issued approvals for twenty-four new therapies for congenital and acquired hematologic conditions.(5) In addition, almost 10,000 new studies for hematologic diseases are currently registered on www.clinicaltrials.gov.(6) With this increase in potential new therapies on the horizon, it is imperative that clinicians and clinical researchers in the field of non-neoplastic hematology have a uniform, secure, unbiased, and enduring method to collect long-term safety and efficacy data. As emphasized in a recently published review, accurate, uniform and quality national data collection is critical in clinical research, particularly for longitudinal cohort studies covering a lifetime of biologic risk.(7)

The overarching objective of this longitudinal, observational study is to characterize the safety, effectiveness and practice of treatments for all people with congenital and acquired hematologic disorders in the US.

Official Title

ATHN Transcends: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment in People With Non-Neoplastic Hematologic Disorders

Details

This is a longitudinal, natural history observational cohort study being conducted at approximately 150 ATHN-affiliated sites. Participants will be followed for a minimum of 15 years. Harmonized data elements will be collected at the time of enrollment, quarterly, annually, and ad hoc. Base data will be collected for all participants. Specific data will be collected for participants enrolled in cohort-specific Arms and Modules.

Each participant will be assigned to a single cohort: Hemophilia, Von Willebrand Disease, Congenital Platelet Disorders, Rare Disorders, Bleeding Not Otherwise Specified (NOS), Thrombosis/Thrombophilia, or Non-Neoplastic Hematologic Conditions.

Study Arms and study Modules may be developed to provision disease and/or disease specific insights related to stakeholders, including but not limited to pharmaceutical companies, ATHN, and Hemophilia Treatment Centers (HTCs). Arms may branch off into product-specific data collection via Modules to be collected during the study, in conjunction with planned study assessments.

ATHN Transcends Principal Investigator: Michael Recht, MD, PhD, MBA American Thrombosis and Hemostasis Network Yale University School of Medicine

Arm Co-Principal Investigators:

PUPs Arm:

Shannon Carpenter, MD, MS University of Missouri Kansas City School of Medicine Children's Mercy Hospital Courtney Thornburg, MD, MS University of California San Diego Rady Children's Hospital San Diego

Hemophilia Natural History Arm:

Tyler Buckner, MD, MSc Hemophilia and Thrombosis Center University of Colorado Anschutz Medical Campus Michael Recht, MD, PhD, MBA American Thrombosis and Hemostasis Network

Hemophilia Gene Therapy Outcomes Arm:

Janice M. Staber, MD Iowa Hemophilia and Thrombosis Center University of Iowa Stead Family Children's Hospital Ulrike M. Reiss, MD Hemophilia Treatment Center St. Jude's Children's Research Hospital

Severe VWD Natural History Arm:

Robert F. Sidonio, Jr., MD, MSc Aflac Cancer and Blood Disorders Center, Hemophilia of Georgia Center for Bleeding and Clotting Disorders Angela C. Weyand, MD C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor

Keywords

Hematologic Disorder, Bleeding Disorder, Connective Tissue Disorder, Hemophilia, Thrombosis, Von Willebrand Diseases, Thrombophilia, Rare Bleeding Disorder, Platelet Disorder, Hemostatic Disorders, Blood Coagulation Disorders, Hemorrhagic Disorders, Hematologic Diseases, Blood Platelet Disorders, Connective Tissue Diseases, Hemorrhage, Congenital Platelet Disorders, Rare Disorders, Thrombosis/Thrombophilia

Eligibility

Participants who meet the following inclusion criteria and none of the exclusion criteria are eligible for enrollment in the base study:

Inclusion Criteria:

  1. Any age
  2. Having a congenital or acquired non-neoplastic hematologic disorder; or
  3. Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or
  4. Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score.

Exclusion Criteria:

  1. Does not qualify for inclusion in a cohort
  2. Unable to give informed consent or assent
  3. Unwilling to perform study procedures

Cohort Participant Selection

Each participant is to be enrolled in the cohort for which they qualify as defined below.

Hemophilia Cohort

Inclusion Criteria:

Participants who meet any of the following inclusion criteria are eligible for enrollment into this cohort:

  1. Factor VIII or factor IX activity < 50%, without another explanation for low clotting factor other than congenital hemophilia or being a known carrier for congenital hemophilia; OR
  2. Being a known carrier for congenital hemophilia with a factor VIII or factor IX activity greater than or equal to 50% with or without a bleeding phenotype as indicated by an age-adjusted abnormal ISTH Bleeding Assessment Tool score; OR
  3. Known congenital hemophilia that have a factor level >50% after receiving vector; OR
  4. Acquired hemophilia

Exclusion Criteria:

None

Von Willebrand Disease Cohort

Inclusion Criteria:

Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:

  1. Meeting the definition of VWD or low VWF per most recent international guidelines

Exclusion Criteria:

None

Congenital Platelet DisorderS Cohort

Inclusion Criteria:

Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:

  1. Abnormalities of platelet function
    1. Glanzmann thrombasthenia (GPIIb or GPIIIa)
    2. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)
  2. Abnormalities of platelet granules
  3. Abnormalities of platelet signal transduction
  4. Abnormalities of platelet secretion
  5. Collagen Receptor Defect
  6. ADP Receptor Defect
  7. Thromboxane Receptor Defect
  8. Giant Platelet Disorder
  9. Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related)

Exclusion Criteria:

Platelet disorders secondary to medications or other substances

Rare Disorders Cohort

Inclusion Criteria:

Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:

  1. Have an established Rare Coagulation Disorder (RCD) diagnosis of one of the following:
  2. PAI-1 deficiency
  3. Factor I, II, V, VII, X, XI, XIII deficiencies
  4. Combined FV and FVIII deficiency
  5. Plasminogen deficiency
  6. Decreased tissue plasminogen activator
  7. Afibrinogenemia/hypofibrinogenemia/dysfibrinogenemia

Exclusion Criteria:

None

Bleeding NOS Cohort

Inclusion Criteria:

Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:

  1. Have a bleeding phenotype as indicated by an age-adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; OR
  2. Connective tissue disorder with bleeding tendency as indicated by an age-adjusted abnormal ISTH Bleeding Assessment Tool score

Exclusion Criteria:

None

Thrombosis/Thrombophilia Cohort

Inclusion Criteria

Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:

  1. Have a prior history of arterial or venous thrombosis
  2. Patients with a known congenital or acquired thrombophilia with or without a thrombosis a. Common congenital thrombophilias:: i. Protein C deficiency ii. Protein S deficiency iii. Antithrombin deficiency iv. Factor V Leiden v. Prothrombin gene mutation b. Rare genetic factors i. Hyperhomocysteinemia c. Indeterminate genetic factors i. Elevated factor VIII ii. Elevated factor IX iii. Elevated factor XI iv. Elevated lipoprotein (a) d. Acquired thrombophilias i. Lupus anticoagulant ii. Anti-cardiolipin antibodies/Beta2 glycoprotein antibodies iii. Antiphospholipid syndrome

Exclusion Criteria

  1. Acquired thrombophilia secondary to medications (birth control pills or hormone replacement therapy, overweight or obesity, smoking, cancer, pregnancy, surgery, injury, prolonged inactivity/bedrest, heart failure, inflammatory bowel disease, or kidney disease

Non-Neoplastic Hematologic Conditions Cohort

Inclusion Criteria

Participants who meet the following inclusion criteria are eligible for enrollment into this cohort:

  1. Having any congenital or acquired non-neoplastic hematologic disorder not included in any other cohort

Exclusion Criteria

None

Locations

  • Hemophilia & Thrombosis Treatment Center at UC San Diego Health accepting new patients
    San Diego California 92121 United States
  • Rady Children's Hospital San Diego accepting new patients
    San Diego California 92123 United States

Lead Scientist at UCSD

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
American Thrombosis and Hemostasis Network
ID
NCT04398628
Study Type
Observational
Participants
Expecting 3000 study participants
Last Updated