ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
Purpose
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. ATHN Transcends is a cohort study to determine the safety, effectiveness, and practice of therapies used in the treatment of participants with congenital or acquired non-neoplastic blood disorders and connective tissue disorders with bleeding tendency. The study consists of 7 cohorts with additional study "arms" and "modules" branching off from the cohorts. 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. 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)
Conditions
- Hematologic Disorder
- Bleeding Disorder
- Connective Tissue Disorder
- Hemophilia
- Thrombosis
- Von Willebrand Diseases
- Thrombophilia
- Rare Bleeding Disorder
- Platelet Disorder
- Factor IX Deficiency
- Factor VIII Deficiency
- Thalassemia
- Sickle Cell Disease
Eligibility
- Eligible Ages
- All ages
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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: 1. PAI-1 deficiency 2. Factor I, II, V, VII, X, XI, XIII deficiencies 3. Combined FV and FVIII deficiency 4. Plasminogen deficiency 5. Decreased tissue plasminogen activator 6. 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
Study Design
- Phase
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
| Hemophilia | This cohort includes three Arms and five Modules: Previously Untreated Patients (PUPs) Arm ALTUVIIIO® Module INHIBIT Module Hemophilia Natural History Arm Hemlibra® Module Rebinyn® Module Hemophilia Gene Therapy Outcomes Arm HEMGENIX® Module | |
| Congenital Platelet Disorders | This cohort includes one Arm and Module: Congenital Platelet Disorders (CPD) Natural History Arm Glanzmann Thrombasthenia (GT) Module | |
| Von Willebrand Disease | No arms or modules | |
| Rare Disorders | No arms or modules | |
| Bleeding NOS | No arms or modules | |
| Thrombosis/Thrombophilia | No arms or modules | |
| Non-Neoplastic Hematologic Conditions | No arms or modules |
Recruiting Locations
New Orleans, Louisiana 70112
More Details
- Status
- Recruiting
- Sponsor
- American Thrombosis and Hemostasis Network
Detailed Description
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 Investigators Tammuella Chrisentery-Singleton, MD Ochsner Clinic Foundation American Thrombosis and Hemostasis Network Michael Recht, MD, PhD, MBA Yale University School of Medicine National Bleeding Disorders Foundation PUPs Arm: Co-Principal Investigators: 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 ALTUVIIO Module: Co-Principal Investigators Shannon Carpenter, MD, MS University of Missouri Kansas City School of Medicine Children's Mercy Hospital Co-Principal Investigator Courtney Thornburg, MD, MS University of California San Diego Rady Children's Hospital San Diego INHIBIT Module: Co-Principal Investigators: Nicoletta Machin DO, MS Assistant Professor, Division of Hematology/Oncology Hemophilia Center of Western Pennsylvania University of Pittsburgh Medical Center Margaret V. Ragni, MD, MPH Professor of Medicine and Clinical Translational Science Department of Medicine Division of Hematology/ Oncology University of Pittsburgh Medical Center Hemophilia Natural History Arm: Co-Principal Investigators: Tyler Buckner, MD, MSc Hemophilia and Thrombosis Center University of Colorado Anschutz Medical Campus Michael Recht, MD, PhD, MBA Yale University School of Medicine National Bleeding Disorders Foundation Rebinyn Module Co-Principal Investigators: Lauren Amos, MD Children's Mercy Hospital, Kansas City Guy Young, MD University of Southern California Children's Hospital Los Angeles Hemophilia Gene Therapy Outcomes Arm: Co-Principal Investigators: 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: Co-Principal Investigators: Robert F. Sidonio, Jr., MD, MSc Aflac Cancer and Blood Disorders Center, Hemophilia of Georgia Center for Bleeding and Clotting Disorders A Angela C. Weyand, MD C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor Congenital Platelet Disorders Natural History Arm: Principal Investigator Sanjay Ahuja, MD Rainbow Babies & Children's Hospital, Case Western Reserve University Glanzmann Thrombasthenia Module: Co-Principal Investigators: Divya Citla-Sridhar, MD University of Arkansas for Medical Sciences Arkansas Children's Hospital Meera Chitlur, MD Children's Hospital of Michigan Hemophilia Cohort This cohort includes three Arms and five Modules: Previously Untreated Patients (PUPs) Arm This is a pediatric focused Arm of PUPs with hemophilia A or B. ALTUVIIIO® Module The purpose is to investigate the safety and effectiveness of ALTUVIIIO® in PUPs with hemophilia A. INHIBIT Module This is an observational study assessing inhibitor formation in children with severe hemophilia A. Hemophilia Natural History Arm This Arm is investigating the safety, effectiveness, and practice of treatment for people with hemophilia. Hemlibra® Module All participants treated with Hemlibra® are eligible to participate. Rebinyn® Module The Rebinyn® Module is a prospective study in hemophilia B participants without inhibitors. Hemophilia Gene Therapy Outcomes Arm This Arm is investigating the safety and effectiveness of gene therapy in people with hemophilia. HEMGENIX® Module This is an observational study to characterize the effectiveness and safety of HEMGENIX® in participants with hemophilia B. Congenital Platelet Disorders (CPD) Natural History Arm: The CPD Arm is investigating the safety and efficacy of hemostatic therapies in the prevention or treatment of bleeding events in adult and pediatric participants with inherited congenital platelet disorders. Glanzmann Thrombasthenia (GT) Module: This Module is a study of bleeding symptoms, treatments, and treatment outcomes in patients with Glanzmann thrombasthenia. Von Willebrand Disease Cohort No arms or modules open at this time. Rare Disorders Cohort No arms or modules open at this time. Bleeding NOS No arms or modules open at this time. Thrombosis/Thrombophilia No arms or modules open at this time. Non-Neoplastic Hematologic Conditions No arms or modules open at this time.