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Data Registry of Auto Immune Hemolytic Anemia (DRAIHA)

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ClinicalTrials.gov Identifier: NCT04024202
Recruitment Status : Recruiting
First Posted : July 18, 2019
Last Update Posted : July 18, 2019
Sponsor:
Collaborators:
Leiden University Medical Center
Radboud University
UMC Utrecht
Maastricht University Medical Center
Erasmus Medical Center
Haga Hospital
Isala
Jeroen Bosch Ziekenhuis
St. Antonius Hospital
Onze Lieve Vrouwe Gasthuis
Spaarne Gasthuis
Amsterdam University Medical Center
Sanquin Plasma Products BV
Information provided by (Responsible Party):
Sanquin Research & Blood Bank Divisions

Brief Summary:

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

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Study Type : Observational
Estimated Enrollment : 720 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine


Group/Cohort
Patients
  1. Patients with a positive DAT, a positive eluate and signs of hemolysis
  2. Patients with a positive DAT with complement only, negative eluate, but with hemolysis
Blood donors
Blood donors with a positive direct antiglobulin test and a positive eluate and/or clinically relevant cold auto-antibodies



Primary Outcome Measures :
  1. 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).

  2. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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


  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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
Blood samples from patients (older than 16 years) and blood donors (older than 18 years) and urine samples from the first 20 included patients in each of the participating hospitals, will be collected for experimental diagnostic testing at inclusion (T0) and after 1-1,5 year (T1) of follow-up.


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Ages Eligible for Study:   3 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients, from the age of 3 months, with a positive DAT a positive eluate and signs of hemolysis and patients with a positive DAT for complement only with a negative eluate but with signs of hemolysis, and blood donors with a positive DAT and a positive eluate and/or clinically relevant cold autoantibodies.
Criteria

Inclusion Criteria:

  • Sufficient comprehension of the Dutch language
  • Signed informed consent by patient and/or parent/caretaker or donor
  • Patients older than 3 months
  • Patients with a positive DAT, a positive eluate and signs of hemolysis*
  • Patients with a positive DAT with complement only, negative eluate, but with signs of hemolysis
  • Donors with a (repeatedly) positive DAT and a positive eluate and/or clinically relevant cold auto-antibodies

Exclusion Criteria:

  • Prior inclusion in the DRAIHA study

Information from the National Library of Medicine

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


Contacts
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Contact: M. Jalink, MD +31205123373 m.jalink@sanquin.nl
Contact: Masja De Haas, Prof. MD PhD +31205123373 m.dehaas@sanquin.nl

Locations
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Netherlands
AMC Not yet recruiting
Amsterdam-Zuidoost, Netherlands
UMC Radboud Recruiting
Nijmegen, Netherlands
Sponsors and Collaborators
Sanquin Research & Blood Bank Divisions
Leiden University Medical Center
Radboud University
UMC Utrecht
Maastricht University Medical Center
Erasmus Medical Center
Haga Hospital
Isala
Jeroen Bosch Ziekenhuis
St. Antonius Hospital
Onze Lieve Vrouwe Gasthuis
Spaarne Gasthuis
Amsterdam University Medical Center
Sanquin Plasma Products BV
Investigators
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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

Publications:

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Responsible Party: Sanquin Research & Blood Bank Divisions
ClinicalTrials.gov Identifier: NCT04024202     History of Changes
Other Study ID Numbers: PPOC 15-27
First Posted: July 18, 2019    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hemolysis
Hematologic Diseases
Pathologic Processes
Autoimmune Diseases
Immune System Diseases