Data Registry of Auto Immune Hemolytic Anemia (DRAIHA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04024202|
Recruitment Status : Recruiting
First Posted : July 18, 2019
Last Update Posted : July 18, 2019
In autoimmune hemolytic anemia (AIHA) auto-antibodies directed against red blood cells (RBCs) lead to increased RBC clearance (hemolysis). This can result in a potentially life-threatening anemia. AIHA is a rare disease with an incidence of 1-3 per 100,000 individuals. An unsolved difficulty in diagnosis of AIHA is the laboratory test accuracy. The current 'golden standard' for AIHA is the direct antiglobulin test (DAT). The DAT detects autoantibody- and/or complement-opsonized RBCs. The DAT has insufficient test characteristics since it remains falsely negative in approximate 5-10% of patients with AIHA, whereas a falsely positive DAT can be found in 8% of hospitalized individuals. Also apparently healthy blood donors can have a positive DAT. The consequences of DAT positivity are not well known and may point to early, asymptomatic disease, or to another disease associated with formation of RBC autoantibodies, such as a malignancy or (systemic) autoimmune disease. Currently, there are no guidelines to follow-up DAT positive donors.
A second unsolved difficulty is the choice of treatment in AIHA. Hemolysis can be stopped or at least attenuated with corticosteroids, aiming to inhibit autoantibody production and/or RBC destruction. Many patients do not respond adequately to corticosteroid treatment or develop severe side effects.
Currently, it is advised to avoid RBC transfusions since these may lead to aggravation of hemolysis and RBC alloantibody formation. But in case symptomatic anemia occurs, RBC transfusions need to be given. An evidence-based transfusion strategy for AIHA patients is needed to warrant safe transfusion in this complex patient group.
To design optimal diagnostic testing and (supportive) treatment algorithms, the investigators will study a group well-characterized patients with AIHA and blood donors without AIHA, via a prospective centralized clinical data collection and evaluation of new laboratory tests. With this data the knowledge of the AIHA pathophysiology and to evaluate diagnostic testing in correlation with clinical features and treatment outcome can be improved.
|Condition or disease|
|Autoimmune Hemolytic Anemia|
|Study Type :||Observational|
|Estimated Enrollment :||720 participants|
|Official Title:||The DRAIHA Study: Data Registry of AutoImmune Hemolytic Anemia, to Improve Diagnostic Testing for the Development of Personalized Treatment Protocols in AIHA Patients|
|Actual Study Start Date :||July 12, 2019|
|Estimated Primary Completion Date :||December 1, 2024|
|Estimated Study Completion Date :||December 1, 2024|
Blood donors with a positive direct antiglobulin test and a positive eluate and/or clinically relevant cold auto-antibodies
- Immunological characteristics of autoantibodies in autoimmune hemolytic anemia (AIHA) patients - laboratory tests. [ Time Frame: 12-18 months ]Documentation of characteristics of autoantibodies (e.g. isotype, subtype, titer, thermal amplitude).
- Assessment of hemolysis before and after therapy, reported per class of auto-immune hemolytic anemia. - laboratory tests [ Time Frame: 12-18 months ]Documentation of hemolysis parameters (hemoglobin level (g/dL), reticulocytes (%), haptoglobin (mg/dL), bilirubin (μmol/L) and LDH(U/L)) before and after each type of therapy. AIHA classification as IgG/IgA only, IgG/IgA with complement activation or complement activation only.
- Incidence of underlying disease that causes or is associated with AIHA. [ Time Frame: 12-18 months ]Documentation of physician-reported underlying disease that caused AIHA (e.g. autoimmune and/or lymphoproliferative disease, infection, medication).
- Type of treatment prescribed as first-line, second-line or further-line treatment for AIHA. [ Time Frame: 12-18 months ]The percentage of patients receiving first, second or further-line treatment for AIHA will be calculated.
- Hematological response after each treatment line (CR, CR-u, PR and NR) [ Time Frame: 12-18 months ]
Percentage of patients with CR, CR-u, PR and NR after each treatment line. Hematological response will be classified as CR (complete remission), CR-u (CR- undetermined), PR (partial response) and NR (no response).
CR: normal hemoglobin, no signs of hemolysis (normal haptoglobin, normal amount of reticulocytes, bilirubin, LDH), no treatment and transfusion independence during the last 4 weeks.
CR-u: as CR, but hemoglobin, reticulocytes, LDH and/or bilirubin are deviating through another reason (e.g. underlying malignant disease).
PR: 1. Hemoglobin > 10g/dL, no signs of hemolysis, transfusion independent, but a continuous treatment with low dose prednisone (< 10 mg/day) or other immunosuppressive therapy is necessary. 2. Compensated hemolytic anemia with an stable hemoglobin >10g/dL, transfusion independent, maximal dose of prednisone < 10mg/day or other continuous immunosuppressive therapy or EPO.
NR: no PR reached
- Relapse-free survival, defined as the time since the achievement of complete or partial remission until relapse of AIHA or dead from any cause. [ Time Frame: 12-18 month ]Relapse-free survival will be calculated as the time since the achievement of complete or partial remission until relapse of AIHA or dead from any cause. Median RFS and 95% CI will be calculated.
- Documentation of adverse events during the treatment of AIHA. [ Time Frame: 12-18 month ]Documentation of adverse events during the treatment of AIHA indicated according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE) Publish Date: May 28, 2009
- Assessment of hemolysis parameters after red blood cell transfusion. [ Time Frame: 1 and 7 days after transfusion ]Documentation of hemolysis parameters (hemoglobin level (g/dL), reticulocytes (%), haptoglobin (mg/dL), bilirubin (μmol/L) and LDH (U/L)) before red blood cell transfusion.
- Change in the incidence of auto- and alloantibodies after red blood cell transfusion. [ Time Frame: 12-18 months ]Compare the incidence of auto- and alloantibodies before and after red blood cell transfusion.
- Characteristics of autoantibodies of DAT positive blood donors. [ Time Frame: 12-18 months ]Documentation of characteristics of autoantibodies (e.g. isotype, subtype, titer, thermal amplitude) of DAT positive blood donors.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04024202
|Contact: M. Jalink, MDfirstname.lastname@example.org|
|Contact: Masja De Haas, Prof. MD PhDemail@example.com|
|AMC||Not yet recruiting|
|Principal Investigator:||M. De Haas, Prof. MD PhD||Center for Clinical Transfusion Research (CCTR), Sanquin, The Netherlands|
|Principal Investigator:||S.S Zeerleder, Prof. MD PhD||University Hospital, University of Bern, Switzerland and Department for BioMedical Research, University of Bern, Switzerland|