Management and Outcomes of Anti-thrombotic Medication Use in Thrombocytopenia

Thrombocytopenia Clinical Trial

— MATTER  

Official title:

Management Patterns of AntiThrombotics and Outcomes in Patients With Hematological Malignancy and ThrombocytopEnia: a Prospective Registry (MATTER Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03288441
• Other study ID #: METC 17-4-061
• Status: Recruiting
• Start date: March 20, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2020
• Source: Maastricht University Medical Center
• Contact: Avi Leader, MD
• Phone: +972-3-9377906
• Email: avileader[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Anticoagulants
• Hematologic Neoplasms
• Platelet Aggregation Inhibitors
• Thrombocytopenia

Intervention

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

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Peta? Tiqwa
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo di Alessandria	Alessandria
Italy	A.O. Papa Giovanni XXIII - S.I.M.T.	Bergamo
Italy	ASST degli Spedali Civili di Brescia	Brescia
Italy	A.O.U. di Modena	Modena
Italy	Ospedale San Gerardo di Monza	Monza
Italy	University Hospital Policlinico di Palermo	Palermo
Italy	A.O.U Policlinico Umberto I di Roma	Roma
Italy	Fondazione Policlinico Universitario A. Gemelli	Roma
Italy	Università degli studi di Roma "Tor Vergata"	Roma
Italy	A.O.U. CITTA' della SALUTE e della SCIENZA di TORINO	Torino
Italy	AZIENDA ULSS N. 8 BERICA di Vicenza	Vicenza
Netherlands	Amsterdam University Medical Centers	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Maastricht University Medical Center (MUMC+)	Maastricht
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	HagaZiekenhuis	The Hague
United States	Oregon Health & Science University Hospital	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Countries where clinical trial is conducted

United States,  Israel,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	peak anticoagulant intensity	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.	3 days after study index
Other	Whole blood coagulation	Measured by rotational thromboelastometry (ROTEM) drawn at study index	3 days after study index
Primary	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	Platelet transfusion related adverse effects	Number of adverse effects (all types and individually grouped) related to platelet/plasma transfusion, occurring within 24 hours of transfusion	30 days (from study index) or until death (whichever first)
Secondary	Clinically Relevant non-Major Bleeding	Defined according to the ISTH criteria published in the journal of thrombosis and Hemostasis by Kaatz et al in 2015	30 days (from study index) or until death (whichever first)
Secondary	Number of platelet tranfusions	Number of platelet transfusions	30 days (from study index) or until death (whichever first)
Secondary	Number of RBC tranfusions	Number of red blood cell transfusions	30 days (from study index) or until death (whichever first)
Secondary	Death	death from any cause	30 days (from study index)
Secondary	Change in antithrombotic management	Change in dose/type of antiplatelet or anticoagulant medication OR change in platelet threshold, AFTER the initial intervention which was recorded at study index.	30 days (from study index) or until death (whichever first)