Clinical trial NCT03288441: Management and Outcomes of Anti-thrombotic Medication Use in Thrombocytopenia
Official title: Management Patterns of AntiThrombotics and Outcomes in Patients With Hematological Malignancy and ThrombocytopEnia: a Prospective Registry (MATTER Study)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hematologic Neoplasms
Thrombocytopenia
Anticoagulants
Platelet Aggregation Inhibitors
Keywords: Hematologic Neoplasms
Thrombocytopenia
Anticoagulants
Platelet Aggregation Inhibitors
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2017-09-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects treated at the inpatient or outpatient hematology departments at the participating centers

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.

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.

Eligibility 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)

Primary outcomes:
measure: Composite of major bleeding or thrombosis
timeFrame: 30 days (from study index) or until death (whichever first)
Secondary outcomes:
measure: Platelet transfusion related adverse effects
timeFrame: 30 days (from study index) or until death (whichever first)
measure: Clinically Relevant non-Major Bleeding
timeFrame: 30 days (from study index) or until death (whichever first)
measure: Number of platelet tranfusions
timeFrame: 30 days (from study index) or until death (whichever first)
measure: Number of RBC tranfusions
timeFrame: 30 days (from study index) or until death (whichever first)
measure: Death
timeFrame: 30 days (from study index)
measure: Change in antithrombotic management
timeFrame: 30 days (from study index) or until death (whichever first)
Other outcomes:
measure: peak anticoagulant intensity
timeFrame: 3 days after study index
measure: Whole blood coagulation
timeFrame: 3 days after study index
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University Hospital
state: Oregon
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petaẖ Tiqwa
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Alessandria
country: Italy
facility: Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo di Alessandria
city: Bergamo
country: Italy
facility: A.O. Papa Giovanni XXIII - S.I.M.T.
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Modena
country: Italy
facility: A.O.U. di Modena
city: Monza
country: Italy
facility: Ospedale San Gerardo di Monza
city: Palermo
country: Italy
facility: University Hospital Policlinico di Palermo
city: Roma
country: Italy
facility: A.O.U Policlinico Umberto I di Roma
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli
city: Roma
country: Italy
facility: Università degli studi di Roma "Tor Vergata"
city: Torino
country: Italy
facility: A.O.U. CITTA' della SALUTE e della SCIENZA di TORINO
city: Vicenza
country: Italy
facility: AZIENDA ULSS N. 8 BERICA di Vicenza
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centers
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center (MUMC+)
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: The Hague
country: Netherlands
facility: HagaZiekenhuis
Study officials:
affiliation: Rabin Medical Center, Petah Tikva, Israel
name: Avi Leader, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Center, Maastricht
name: Hugo ten Cate, MD, PhD
role: STUDY_CHAIR
affiliation: A.O. Papa Giovanni XXIII - S.I.M.T.
name: Anna Falanga, MD
role: STUDY_CHAIR
References: