Management and Outcomes of Anti-thrombotic Medication Use in Thrombocytopenia

NCT ID: NCT03288441

Last Updated: 2020-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-03-20

Study Completion Date

2021-12-31

Brief Summary

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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.

Detailed Description

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* Thrombocyte-level cohorts Patients will be divided into two groups based on the platelet level at study index .

1. Thrombocytopenic Cohort: Patients with morning platelet count below 50\*109/L at study index. This is the main study cohort for all analyses
2. Non-thrombocytopenic Cohort: Patients whose morning platelet count is ≥ 50\*109/L at study index will be considered as a reference group, and not included in the primary analysis.
* Analysis of outcomes:

By definition, there will be an intervention at the time of study index (baseline), meaning that even if no change is made, it will be considered an intervention. Each patient may have multiple exposures/interventions over the study.

Therefore, in a time dependent analysis, each outcome will be linked to the exposure/intervention at study index.

Each exposure/intervention will be linked with the platelet level on the day of the intervention.

#Competing Events:

The following events (in addition to death) will be considered competing events and will be considered as such in the statistical analyses of the outcomes:

1. The composite primary outcome
2. change in the antithrombotic regimen after study index
3. diagnosis of HIT or TTP
4. a change in the hematological malignancy treatment regimen. Study follow-up will continue after these events, and study data will continue to be recorded until censorship for end of study period or death.

* Detecting selection bias:

Patients fulfilling the inclusion criteria but not included in the study, will be detected by reviewing the medical records of the hematology institute, weekly. The baseline characteristics and reason for not including these patients will be recorded retrospectively in the "not-included cohort". The baseline characteristics of this cohort will be compared with the study cohort to ascertain whether selection bias exists.

Conditions

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Hematologic Neoplasms Thrombocytopenia Anticoagulants Platelet Aggregation Inhibitors

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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)

Hold

Intervention Type DRUG

Hold antithrombotic therapy

Change antithrombotic Drug

Intervention Type DRUG

Change in type of antithrombotic therapy

Change platelet transfusion threshold

Intervention Type BIOLOGICAL

Increase or reduce platelet transfusion threshold

Full dose antithrombotics

Intervention Type DRUG

Continue full dose antithrombotic therapy

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)

Hold

Intervention Type DRUG

Hold antithrombotic therapy

Prophylactic dose antithrombotic

Intervention Type DRUG

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

Change antithrombotic Drug

Intervention Type DRUG

Change in type of antithrombotic therapy

Change platelet transfusion threshold

Intervention Type BIOLOGICAL

Increase or reduce platelet transfusion threshold

Full dose antithrombotics

Intervention Type DRUG

Continue full dose antithrombotic therapy

Mechanical measures

Intervention Type DEVICE

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

Intermediate dose antithrombotic

Intervention Type DRUG

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

Interventions

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Hold

Hold antithrombotic therapy

Intervention Type DRUG

Prophylactic dose antithrombotic

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

Intervention Type DRUG

Change antithrombotic Drug

Change in type of antithrombotic therapy

Intervention Type DRUG

Change platelet transfusion threshold

Increase or reduce platelet transfusion threshold

Intervention Type BIOLOGICAL

Full dose antithrombotics

Continue full dose antithrombotic therapy

Intervention Type DRUG

Mechanical measures

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

Intervention Type DEVICE

Intermediate dose antithrombotic

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Maastricht University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Avi Leader, MD

Role: PRINCIPAL_INVESTIGATOR

Rabin Medical Center, Petah Tikva, Israel

Hugo ten Cate, MD, PhD

Role: STUDY_CHAIR

Maastricht University Medical Center, Maastricht

Anna Falanga, MD

Role: STUDY_CHAIR

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

Locations

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Oregon Health & Science University Hospital

Portland, Oregon, United States

Site Status TERMINATED

Rambam Health Care Campus

Haifa, , Israel

Site Status RECRUITING

Meir Medical Center

Kfar Saba, , Israel

Site Status RECRUITING

Rabin Medical Center

Petah Tikva, , Israel

Site Status RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status RECRUITING

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

Alessandria, , Italy

Site Status RECRUITING

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

Bergamo, , Italy

Site Status RECRUITING

ASST degli Spedali Civili di Brescia

Brescia, , Italy

Site Status RECRUITING

A.O.U. di Modena

Modena, , Italy

Site Status NOT_YET_RECRUITING

Ospedale San Gerardo di Monza

Monza, , Italy

Site Status RECRUITING

University Hospital Policlinico di Palermo

Palermo, , Italy

Site Status RECRUITING

A.O.U Policlinico Umberto I di Roma

Roma, , Italy

Site Status RECRUITING

Fondazione Policlinico Universitario A. Gemelli

Roma, , Italy

Site Status RECRUITING

Università degli studi di Roma "Tor Vergata"

Roma, , Italy

Site Status RECRUITING

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

Torino, , Italy

Site Status RECRUITING

AZIENDA ULSS N. 8 BERICA di Vicenza

Vicenza, , Italy

Site Status NOT_YET_RECRUITING

Amsterdam University Medical Centers

Amsterdam, , Netherlands

Site Status RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status RECRUITING

Maastricht University Medical Center (MUMC+)

Maastricht, , Netherlands

Site Status RECRUITING

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status RECRUITING

HagaZiekenhuis

The Hague, , Netherlands

Site Status WITHDRAWN

Countries

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United States Israel Italy Netherlands

Central Contacts

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Avi Leader, MD

Role: CONTACT

+972-3-9377906

Hugo ten Cate, MD, PhD

Role: CONTACT

Facility Contacts

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Yona Nadir, MD, PhD

Role: primary

Debbie Steiner, MHA

Role: backup

+972-4-8543592

Orly Avnery, MD

Role: primary

+972-9-7471755

Galia Spectre, MD, PhD

Role: primary

+972-3-9377906

Ron Ram, MD

Role: primary

+972-3-697-3577

Dr. Roberto Santi

Role: primary

+39 (0)131 206111

Anna Falanga, MD

Role: primary

+39-035.267.8597

Alessandro Rambaldi, MD

Role: backup

Dr. Giuseppe Rossi

Role: primary

+39 (0)30 399 8870

Dr. Marco Marietta

Role: primary

+39 (0)59 422 2111

Andrea Carrer

Role: primary

Sergio Siragusa, MD

Role: primary

Mariasanta Napolitano

Role: backup

+39-91 655 1111

Dr. Antonio Chistolini

Role: primary

+39 06 49971

Prof. Valerio De Stefano

Role: primary

+39 06 30151

Maria Ilaria Del Principe

Role: primary

Eloise Beggiato, MD

Role: primary

+39-11 633 1633

Dr. Marco Ruggeri

Role: primary

+39 (0)444 753111

Harry R Büller, MD, PhD

Role: primary

Eva N Hamulyák, MD

Role: backup

+31 20 5667516

Karina Meijer, MD, PhD

Role: primary

Tessa Elling, MD

Role: backup

+31 6 31623491

Avi Leader, MD

Role: primary

+31-43-3874780

Mandy Lauw, MD, PhD

Role: primary

Other Identifiers

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METC 17-4-061

Identifier Type: -

Identifier Source: org_study_id

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