NCT01257269

Brief Summary

Hereditary thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) is a rare disorder characterized by thrombocytopenia as a result of platelet consumption, microangiopathic hemolytic anemia, occlusion of the microvasculature with von Willebrand factor-platelet-thrombic and ischemic end organ damage. The underlying patho-mechanism is a severe congenital ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) deficiency which is the result of compound heterozygous or homozygous ADAMTS13 gene mutations. Although considered a monogenic disorder the clinical presentation in Upshaw-Schulman syndrome patients varies considerably without an apparent genotype-phenotype correlation. In 2006 we have initiated a registry for patients with Upshaw-Schulman syndrome and their family members to identify possible triggers of acute bouts of TTP, to document individual clinical courses and treatment requirements as well as possible side effects of long standing plasma substitution, e.g. alloantibody formation or viral infections.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
450

participants targeted

Target at P75+ for all trials

Timeline
53mo left

Started Oct 2006

Longer than P75 for all trials

Geographic Reach
7 countries

7 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress82%
Oct 2006Oct 2030

Study Start

First participant enrolled

October 1, 2006

Completed
4.2 years until next milestone

First Submitted

Initial submission to the registry

December 6, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 9, 2010

Completed
19.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2030

Last Updated

October 11, 2023

Status Verified

October 1, 2023

Enrollment Period

24 years

First QC Date

December 6, 2010

Last Update Submit

October 10, 2023

Conditions

Thrombotic Thrombocytopenic PurpuraCongenital Thrombotic Thrombocytopenic PurpuraFamilial Thrombotic Thrombocytopenic PurpuraThrombotic Thrombocytopenic Purpura, CongenitalUpshaw-Schulman Syndrome

Keywords

Thrombotic thrombocytopenic purpuraADAMTS13Von Willebrand factorVon Willebrand factor cleaving proteaseThrombocytopeniaHemolytic anemia

Outcome Measures

Primary Outcomes (1)

  • Clinical presentation and disease course in hereditary TTP

    every year until death

Secondary Outcomes (5)

  • Identification of disease-modifying factors, including genotype-phenotype correlation

    every year until death

  • Treatment requirements in hereditary TTP patients

    every year until death

  • Documentation of potential adversary effects of (long-term) plasma treatment

    every year until death

  • Mortality of hereditary TTP

    every year until death

  • Clinical course in family members

    every year until death

Study Arms (2)

1

Patients with confirmed hereditary TTP due to congenital ADAMTS13 deficiency

Other: Observation

2

Family members of patients with confirmed hereditary TTP

Other: Observation

Interventions

ObservationOTHER

No interventions planned: treatment of patients at the discretion of the treating/responsible physician

12

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients with either confirmed or with suspected hereditary TTP and their family members are eligible for enrollment

You may qualify if:

  • Severe ADAMTS13 deficiency ( ≤ 10% activity) and no ADAMTS 13 inhibitor on two or more occasions at least one month apart
  • Being a family member of a confirmed or suspected patient
  • Molecular analysis of ADAMTS13 gene with one or more mutations and/or positive infusion trial (full recovered ADAMTS13 activity after infused fresh frozen plasma (FFP) with a plasma half-life of 2-4 days)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

University of Oklahoma Health Sciences Center, Department of Medicine, PO Box 26901

Oklahoma City, Oklahoma, 73126-0901, United States

RECRUITING

Medical University of Vienna, Department of Medicine 1, Div. Hematology and Hemostasis Waehringer Guertel 18-20

Vienna, A-1090, Austria

RECRUITING

Institute of Hematology and Blood Transfusion, Coagulation Laboratory, U nemocnice 1

Prague, CZ-12820, Czechia

RECRUITING

University Medical Center Hamburg-Eppendorf, Department of Pediatric Hematology and Oncology, Martinistr 52

Hamburg, D-20246, Germany

NOT YET RECRUITING

Nara Medical University, Department of Blood Transfusion Medicine, Shijyo-cho 840

Kashihara, Nara, 634-8522, Japan

RECRUITING

Trondheim University St Olavs Hospital, Department of Hematology, PO Box 3250 Sluppen

Trondheim, NO-7006, Norway

RECRUITING

University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital and the University of Bern, Inselspital

Bern, 3010, Switzerland

RECRUITING

Related Publications (5)

  • Tarasco E, Butikofer L, Friedman KD, George JN, Hrachovinova I, Knobl PN, Matsumoto M, von Krogh AS, Aebi-Huber I, Cermakova Z, Gorska-Kosicka M, Jalowiec KA, Largiader CR, Prohaszka Z, Sinkovits G, Windyga J, Lammle B, Kremer Hovinga JA. Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura. Blood. 2021 Jun 24;137(25):3563-3575. doi: 10.1182/blood.2020009801.

    PMID: 33649760DERIVED

  • van Dorland HA, Taleghani MM, Sakai K, Friedman KD, George JN, Hrachovinova I, Knobl PN, von Krogh AS, Schneppenheim R, Aebi-Huber I, Butikofer L, Largiader CR, Cermakova Z, Kokame K, Miyata T, Yagi H, Terrell DR, Vesely SK, Matsumoto M, Lammle B, Fujimura Y, Kremer Hovinga JA; Hereditary TTP Registry. The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: key findings at enrollment until 2017. Haematologica. 2019 Oct;104(10):2107-2115. doi: 10.3324/haematol.2019.216796. Epub 2019 Feb 21.

    PMID: 30792199DERIVED

  • Fan X, Kremer Hovinga JA, Shirotani-Ikejima H, Eura Y, Hirai H, Honda S, Kokame K, Taleghani MM, von Krogh AS, Yoshida Y, Fujimura Y, Lammle B, Miyata T. Genetic variations in complement factors in patients with congenital thrombotic thrombocytopenic purpura with renal insufficiency. Int J Hematol. 2016 Mar;103(3):283-91. doi: 10.1007/s12185-015-1933-7. Epub 2016 Feb 1.

    PMID: 26830967DERIVED

  • Lammle B. VWF and complement. Blood. 2015 Feb 5;125(6):896-8. doi: 10.1182/blood-2014-12-612556. No abstract available.

    PMID: 25655456DERIVED

  • Mansouri Taleghani M, von Krogh AS, Fujimura Y, George JN, Hrachovinova I, Knobl PN, Quist-Paulsen P, Schneppenheim R, Lammle B, Kremer Hovinga JA. Hereditary thrombotic thrombocytopenic purpura and the hereditary TTP registry. Hamostaseologie. 2013 May 29;33(2):138-43. doi: 10.5482/HAMO-13-04-0026.

    PMID: 23715103DERIVED

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood and plasma

MeSH Terms

Conditions

Purpura, Thrombotic ThrombocytopenicThrombocytopeniaAnemia, Hemolytic

Interventions

Observation

Condition Hierarchy (Ancestors)

Purpura, ThrombocytopenicPurpuraBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesThrombotic MicroangiopathiesBlood Platelet DisordersCytopeniaThrombophiliaHemorrhagePathologic ProcessesPathological Conditions, Signs and SymptomsSkin ManifestationsSigns and SymptomsAnemia

Intervention Hierarchy (Ancestors)

MethodsInvestigative Techniques

Study Officials

  • Johanna A Kremer Hovinga, MD

    University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital and the University of Bern, Inselspital

    STUDY CHAIR

  • Bernhard Lämmle, M.D.

    University Medical Center, Center for Thrombosis and Hemostasis, Mainz, Germany

    STUDY CHAIR

  • Yoshihiro Fujimura, M.D.

    Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan

    STUDY CHAIR

  • Ingrid Hrachovinova, Ph.D.

    Institute of Hematology and Blood Transfusion, Coagulation Laboratory, Prague, Czech Republic

    STUDY CHAIR

  • Petter Quist-Paulsen, M.D., Ph.D.

    Department of Hematology, St Olavs Hospital, 7006 Trondheim, Norway

    STUDY CHAIR

  • Reinhard Schneppenheim, M.D., Ph.D.

    Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    STUDY CHAIR

  • James N. George, MD

    University of Oklahoma Health Sciences Center, Department of Medicine, United States of America

    STUDY CHAIR

  • Paul N Knoebl, MD

    Medical University of Vienna, Div. Hematology and Hemostasis, Austria

    STUDY CHAIR

Central Study Contacts

Johanna A Kremer Hovinga, MD

CONTACT

+41 31 632 02 65johanna.kremer@insel.ch

Marissa Schraner, Ph.D.

CONTACT

+41 31 632 56 90marissa.schraner@insel.ch

Study Design

Study Type
observational
Observational Model
CASE ONLY
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 6, 2010

First Posted

December 9, 2010

Study Start

October 1, 2006

Primary Completion (Estimated)

October 1, 2030

Study Completion (Estimated)

October 1, 2030

Last Updated

October 11, 2023

Record last verified: 2023-10

Locations

JP(1)AU(1)CH(1)CZ(1)US(1)DE(1)NO(1)