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Management and Outcomes of Anti-thrombotic Medication Use in Thrombocytopenia (MATTER)

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ClinicalTrials.gov Identifier: NCT03288441
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : November 26, 2018
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center

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.


Condition or disease Intervention/treatment
Hematologic Neoplasms Thrombocytopenia Anticoagulants Platelet Aggregation Inhibitors Drug: Hold Drug: Prophylactic dose antithrombotic Drug: Change antithrombotic Drug Biological: Change platelet transfusion threshold Drug: Full dose antithrombotics Device: Mechanical measures Drug: Intermediate dose antithrombotic

Detailed Description:
  • 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.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 6 Months
Official Title: Management Patterns of AntiThrombotics and Outcomes in Patients With Hematological Malignancy and ThrombocytopEnia: a Prospective Registry (MATTER Study)
Actual Study Start Date : March 20, 2018
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Group/Cohort Intervention/treatment
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: Hold
Hold antithrombotic therapy

Drug: Change antithrombotic Drug
Change in type of antithrombotic therapy

Biological: Change platelet transfusion threshold
Increase or reduce platelet transfusion threshold

Drug: Full dose antithrombotics
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)

Drug: Hold
Hold antithrombotic therapy

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

Drug: Change antithrombotic Drug
Change in type of antithrombotic therapy

Biological: Change platelet transfusion threshold
Increase or reduce platelet transfusion threshold

Drug: Full dose antithrombotics
Continue full dose antithrombotic therapy

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

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




Primary Outcome Measures :
  1. Composite of major bleeding or thrombosis [ Time Frame: 30 days (from study index) or until death (whichever first) ]
    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.


Secondary Outcome Measures :
  1. Platelet transfusion related adverse effects [ Time Frame: 30 days (from study index) or until death (whichever first) ]
    Number of adverse effects (all types and individually grouped) related to platelet/plasma transfusion, occurring within 24 hours of transfusion

  2. Clinically Relevant non-Major Bleeding [ Time Frame: 30 days (from study index) or until death (whichever first) ]
    Defined according to the ISTH criteria published in the journal of thrombosis and Hemostasis by Kaatz et al in 2015

  3. Number of platelet tranfusions [ Time Frame: 30 days (from study index) or until death (whichever first) ]
    Number of platelet transfusions

  4. Number of RBC tranfusions [ Time Frame: 30 days (from study index) or until death (whichever first) ]
    Number of red blood cell transfusions

  5. Death [ Time Frame: 30 days (from study index) ]
    death from any cause

  6. Change in antithrombotic management [ Time Frame: 30 days (from study index) or until death (whichever first) ]
    Change in dose/type of antiplatelet or anticoagulant medication OR change in platelet threshold, AFTER the initial intervention which was recorded at study index.


Other Outcome Measures:
  1. peak anticoagulant intensity [ Time Frame: 3 days after study index ]
    anti-Xa, Hemoclot, INR, aPTT will be measured at peak, depending on the anticoagulant drug. Patients will be classified as having sub-therapeutic, therapeutic, supra-therapeutic treatment levels, based upon the reference range at the central laboratory. Only relevant for patients with anticoagulation undergoing dose change.

  2. Whole blood coagulation [ Time Frame: 3 days after study index ]
    Measured by rotational thromboelastometry (ROTEM) drawn at study index


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.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects treated at the inpatient or outpatient hematology departments at the participating centers
Criteria

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)

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): NCT03288441


Contacts
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Contact: Avi Leader, MD +972-3-9377906 avileader@yahoo.com
Contact: Hugo ten Cate, MD, PhD h.tencate@maastrichtuniversity.nl

Locations
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United States, Oregon
Oregon Health & Science University Hospital Recruiting
Portland, Oregon, United States, 97239
Contact: Bethany Samuelson, MD    503-494-8311    samuelsb@ohsu.edu   
Israel
Rambam Health Care Campus Not yet recruiting
Haifa, Israel
Contact: Yona Nadir, MD, PhD         
Contact: Debbie Steiner, MHA    +972-4-8543592    d_steiner@rambam.health.gov.il   
Meir Medical Center Recruiting
Kfar Saba, Israel, 4428164
Contact: Orly Avnery, MD    +972-9-7471755    avneryho@clalit.org.il   
Rabin Medical Center Recruiting
Petaẖ Tiqwa, Israel
Contact: Galia Spectre, MD, PhD    +972-3-9377906    galiasp1@clalit.org.il   
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Contact: Ron Ram, MD    +972-3-697-3577    ronr@tlvmc.gov.il   
Italy
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo di Alessandria Not yet recruiting
Alessandria, Italy, 15121
Contact: Dr. Roberto Santi    +39 (0)131 206111    dr.rsanti@gmail.com   
A.O. Papa Giovanni XXIII - S.I.M.T. Recruiting
Bergamo, Italy, 24127
Contact: Anna Falanga, MD    +39-035.267.8597    annafalanga@icthic.com   
Contact: Alessandro Rambaldi, MD       arambaldi@asst-pg23.it   
ASST degli Spedali Civili di Brescia Recruiting
Brescia, Italy, 25123
Contact: Dr. Giuseppe Rossi    +39 (0)30 399 8870    giuseppe.rossi@asst-spedalicivili.it   
A.O.U. di Modena Not yet recruiting
Modena, Italy, 41125
Contact: Dr. Marco Marietta    +39 (0)59 422 2111    marco.marietta1@gmail.com   
University Hospital Policlinico di Palermo Recruiting
Palermo, Italy
Contact: Sergio Siragusa, MD         
Contact: Mariasanta Napolitano    +39-91 655 1111    mariasanta.napolitano@unipa.it   
A.O.U Policlinico Umberto I di Roma Recruiting
Roma, Italy, 00161
Contact: Dr. Antonio Chistolini    +39 06 49971    chistolini@bce.uniroma1.it   
Fondazione Policlinico Universitario A. Gemelli Recruiting
Roma, Italy, 00168
Contact: Prof. Valerio De Stefano    +39 06 30151    valerio.destefano@unicatt.it   
A.O.U. CITTA' della SALUTE e della SCIENZA di TORINO Not yet recruiting
Torino, Italy
Contact: Eloise Beggiato, MD    +39-11 633 1633    ebeggiato@cittadellasalute.to.it   
AZIENDA ULSS N. 8 BERICA di Vicenza Not yet recruiting
Vicenza, Italy, 36100
Contact: Dr. Marco Ruggeri    +39 (0)444 753111    marco.ruggeri@ulssvicenza.it   
Netherlands
Amsterdam University Medical Centers Not yet recruiting
Amsterdam, Netherlands
Contact: Harry R Büller, MD, PhD       h.r.buller@amc.uva.nl   
Contact: Eva N Hamulyák, MD    +31 20 5667516    e.n.hamulyak@amc.uva.nl   
University Medical Center Groningen Not yet recruiting
Groningen, Netherlands
Contact: Karina Meijer, MD, PhD       k.meijer@umcg.nl   
Contact: Jasper van Miert, MD    +31 6 31623491    j.h.a.van.miert@umcg.nl   
Maastricht University Medical Center (MUMC+) Recruiting
Maastricht, Netherlands, 6229 HX
Contact: Avi Leader, MD    +31-43-3874780    avileader@yahoo.com   
HagaZiekenhuis Not yet recruiting
The Hague, Netherlands, 2545 AA
Contact: Paula Ypma, MD    0702102655    p.ypma@hagaziekenhuis.nl   
Sponsors and Collaborators
Maastricht University Medical Center
Investigators
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Principal Investigator: Avi Leader, MD Rabin Medical Center, Petah Tikva, Israel
Study Chair: Hugo ten Cate, MD, PhD Maastricht University Medical Center, Maastricht
Study Chair: Anna Falanga, MD A.O. Papa Giovanni XXIII - S.I.M.T.

Additional Information:

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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT03288441     History of Changes
Other Study ID Numbers: METC 17-4-061
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maastricht University Medical Center:
Hematologic Neoplasms
Thrombocytopenia
Anticoagulants
Platelet Aggregation Inhibitors

Additional relevant MeSH terms:
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Thrombocytopenia
Hematologic Neoplasms
Blood Platelet Disorders
Hematologic Diseases
Neoplasms by Site
Neoplasms
Anticoagulants
Platelet Aggregation Inhibitors