NCT03288441

Management and Outcomes of Anti-thrombotic Medication Use in Thrombocytopenia

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

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 300 (estimated)
• Sponsor: Maastricht University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Hematologic Neoplasms
• Thrombocytopenia
• Anticoagulants
• Platelet Aggregation Inhibitors

Interventions

Type	Name	Description
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

Timeline

• Start date: 2018-03-20
• Primary completion: 2020-12-31
• Completion: 2021-12-31
• First posted: 2017-09-20
• Last updated: 2020-09-17

Locations

21 sites across 4 countries: United States, Israel, Italy, Netherlands