NCT03288441

Brief Summary

Background: Antithrombotic therapy in the context of treatment related thrombocytopenia (i.e. low levels of platelets) is not uncommon. Guidelines are based upon a paucity of retrospective data and focus on the scenario of cancer associated venous thrombosis and low molecular weight heparin treatment. Even less is known regarding direct oral anticoagulants, antiplatelet therapy, or anticoagulation prescribed for other indications. Aims: The study aims are to evaluate how physicians manage anticoagulant and antiplatelet medication in patients with hematological malignancy and thrombocytopenia, and to assess the frequency of bleeding and thrombosis. Additional aims are to assess how management changes affect drug activity and blood clotting (coagulation), and to evaluate the use of platelet transfusions. Design: The investigators plan a multinational prospective registry of patients admitted to the inpatient hematology department or outpatient clinic at one of the study centers. Patients with hematological malignancies, platelets below 50 X 109/L, and anticoagulant and/or antiplatelet medication will be studied. Patients will be enrolled when the combination of antiplatelet/anticoagulant medication and thrombocytopenia is first detected. Patients will be followed until 30 days after the baseline study visit (which occurs 30 days after enrollment or when platelets \< 50\*109/L, whichever come first) or death. Patients will be indexed at the time of baseline visit. Patients will be excluded from study analysis if one of the following events occurs before study index: Withdrawal of consent, death, clinically-relevant non-major bleeding or the composite primary outcome. Risk factors for bleeding and thrombosis will be recorded at baseline. Parameters from routine blood tests will be recorded throughout the study. During the study major bleeding events and thrombosis will be recorded. Investigational blood tests assessing coagulation and drug activity will be drawn at baseline (=study index). Throughout the study all management decisions regarding antithrombotic therapy, including platelet and red blood cell transfusion, will be recorded. This is an observational study and management will be solely at the discretion of the physician. Analysis: The investigators will first look at the frequency of either bleeding or thrombosis according to the type of management strategy and evaluate the platelet threshold at which a given management strategy is employed. At the next stage, in selected subgroups, the optimal management strategy with respect to bleeding/thrombotic risk, will be determined.

Trial Health

47
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2018

Typical duration for all trials

Geographic Reach
4 countries

21 active sites

Status
unknown

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

First Submitted

Initial submission to the registry

September 7, 2017

Completed
13 days until next milestone

First Posted

Study publicly available on registry

September 20, 2017

Completed
6 months until next milestone

Study Start

First participant enrolled

March 20, 2018

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2021

Completed
Last Updated

September 17, 2020

Status Verified

September 1, 2020

Enrollment Period

2.8 years

First QC Date

September 7, 2017

Last Update Submit

September 16, 2020

Conditions

Keywords

Hematologic NeoplasmsThrombocytopeniaAnticoagulantsPlatelet Aggregation Inhibitors

Outcome Measures

Primary Outcomes (1)

  • Composite of major bleeding or thrombosis

    1\) ISTH-defined Major bleeding events defined as: Fatal bleeding; bleeding into a critical organ; clinically overt bleeding associated with a decrease in hemoglobin level of more than 2 g/dL or leading to the transfusion of two or more units of blood OR: 2) Thrombosis defined as: Any symptomatic deep or superficial venous or arterial thromboembolism demonstrated on objective imaging/laboratory tests. Ischemic strokes with no immediate imaging signs will also be considered events, provided this was diagnosed by a neurologist and that the patient had objective neurological signs.

    30 days (from study index) or until death (whichever first)

Secondary Outcomes (6)

  • Platelet transfusion related adverse effects

    30 days (from study index) or until death (whichever first)

  • Clinically Relevant non-Major Bleeding

    30 days (from study index) or until death (whichever first)

  • Number of platelet tranfusions

    30 days (from study index) or until death (whichever first)

  • Number of RBC tranfusions

    30 days (from study index) or until death (whichever first)

  • Death

    30 days (from study index)

  • +1 more secondary outcomes

Other Outcomes (2)

  • peak anticoagulant intensity

    3 days after study index

  • Whole blood coagulation

    3 days after study index

Study Arms (2)

antiplatelet only

Patients receiving antiplatelet medication, but not anticoagulation. Antiplatelet drugs include any class, dose or duration of any platelet aggregation inhibitor. This refers to the antithrombotic regimen when the current thrombocytopenia, or risk thereof (i.e. "predicted"), was first identified (even if the treatment is subsequently stopped)

Drug: HoldDrug: Change antithrombotic DrugBiological: Change platelet transfusion thresholdDrug: Full dose antithrombotics

anticoagulant-based

Patients receiving only anticoagulants or both anticoagulant and antiplatelet medication combined. This includes any class, dose or duration of any antiplatelet or anticoagulant drug. This refers to the antithrombotic regimen when the current thrombocytopenia, or risk thereof (i.e. "predicted"), was first identified (even if the treatment is subsequently stopped)

Drug: HoldDrug: Prophylactic dose antithromboticDrug: Change antithrombotic DrugBiological: Change platelet transfusion thresholdDrug: Full dose antithromboticsDevice: Mechanical measuresDrug: Intermediate dose antithrombotic

Interventions

HoldDRUG

Hold antithrombotic therapy

anticoagulant-basedantiplatelet only

Reduction in antithrombotic medication dose to prophylactic dose (without changing type)

anticoagulant-based

Change in type of antithrombotic therapy

anticoagulant-basedantiplatelet only

Increase or reduce platelet transfusion threshold

anticoagulant-basedantiplatelet only

Continue full dose antithrombotic therapy

anticoagulant-basedantiplatelet only

Mechanical measures to reduce thrombotic risk including: IVC filter insertion, Intermittent Pneumatic Compression (IPC), Removal of Central venous catheter

anticoagulant-based

Reduction in antithrombotic medication dose to prophylactic dose (without changing type). Intermediate dose in between prophylactic and full dose

anticoagulant-based

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Subjects treated at the inpatient or outpatient hematology departments at the participating centers

You may qualify if:

  • Any hematological malignancy with or without active treatment (including autologous or allogeneic stem cell transplantation), irrespective of the treatment line and disease status.
  • Disease-related and/or current/predicted treatment-related thrombocytopenia (\<50 X 109/L) of any duration.
  • Current antiplatelet and/or anticoagulant treatment of any duration and for any indication. This treatment may have been started before or after diagnosis of the hematological malignancy and thrombocytopenia.
  • "Current" refers to the time when the current thrombocytopenia, or risk thereof (i.e. "predicted"), was first identified (even if the treatment is subsequently stopped)

You may not qualify if:

  • Previous thrombocytopenia (\<50 X 109/L) while using the current antithrombotic regimen.
  • Current diagnosis of heparin induced thrombocytopenia (HIT) or thrombotic thrombocytopenia purpura (TTP)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Oregon Health & Science University Hospital

Portland, Oregon, 97239, United States

TERMINATED

Rambam Health Care Campus

Haifa, Israel

RECRUITING

Meir Medical Center

Kfar Saba, 4428164, Israel

RECRUITING

Rabin Medical Center

Petah Tikva, Israel

RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

RECRUITING

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo di Alessandria

Alessandria, 15121, Italy

RECRUITING

A.O. Papa Giovanni XXIII - S.I.M.T.

Bergamo, 24127, Italy

RECRUITING

ASST degli Spedali Civili di Brescia

Brescia, 25123, Italy

RECRUITING

A.O.U. di Modena

Modena, 41125, Italy

NOT YET RECRUITING

Ospedale San Gerardo di Monza

Monza, Italy

RECRUITING

University Hospital Policlinico di Palermo

Palermo, Italy

RECRUITING

A.O.U Policlinico Umberto I di Roma

Roma, 00161, Italy

RECRUITING

Fondazione Policlinico Universitario A. Gemelli

Roma, 00168, Italy

RECRUITING

Università degli studi di Roma "Tor Vergata"

Roma, Italy

RECRUITING

A.O.U. CITTA' della SALUTE e della SCIENZA di TORINO

Torino, Italy

RECRUITING

AZIENDA ULSS N. 8 BERICA di Vicenza

Vicenza, 36100, Italy

NOT YET RECRUITING

Amsterdam University Medical Centers

Amsterdam, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Maastricht University Medical Center (MUMC+)

Maastricht, 6229 HX, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, Netherlands

RECRUITING

HagaZiekenhuis

The Hague, 2545 AA, Netherlands

WITHDRAWN

Biospecimen

Retention: SAMPLES WITHOUT DNA

After measuring the activity of anticoagulant drugs from the plasma when doses are modified, remaining plasma will be retained for 5 years.

MeSH Terms

Conditions

Hematologic NeoplasmsThrombocytopenia

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBlood Platelet DisordersCytopenia

Study Officials

  • Avi Leader, MD

    Rabin Medical Center, Petah Tikva, Israel

    PRINCIPAL INVESTIGATOR
  • Hugo ten Cate, MD, PhD

    Maastricht University Medical Center, Maastricht

    STUDY CHAIR
  • Anna Falanga, MD

    A.O. Papa Giovanni XXIII - S.I.M.T.

    STUDY CHAIR

Central Study Contacts

Hugo ten Cate, MD, PhD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
6 Months
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 7, 2017

First Posted

September 20, 2017

Study Start

March 20, 2018

Primary Completion

December 31, 2020

Study Completion

December 31, 2021

Last Updated

September 17, 2020

Record last verified: 2020-09

Locations