STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis

Ottawa Hospital Research Institute

Status and phase: Enrolling; Phase 4

Conditions: Thrombocytopenia; Cancer-associated Thrombosis

Treatments: Biological: Enoxaparin; Biological: Tinzaparin; Biological: Dalteparin

Study type: Interventional

Funder types: Other

Identifiers

NCT05255003

START Pilot

Details and patient eligibility

About

Patients with cancer are prone to have blood clots, which are usually treated with blood thinners. The main complication of blood thinners is bleeding. This is especially a concern when the number of platelets in the blood is lower than 50,000 per microliter. The role of platelets is to stop bleeding, so when the number of platelets is low, patients are at a higher risk of bleeding. Cancer patients are prone to have lower platelet numbers due to cancer therapies and/or cancer itself. It is not clear what the best treatment is for cancer patients who need blood thinners for a blood clot but have low platelet counts.

The investigators plan to do a small study called a pilot study to help plan for a larger study in such patients. In the pilot study, investigators will include 50 patients with cancer, low platelet counts, and a blood clot diagnosed within 4 weeks. Patients will be randomly assigned to one of the two treatment strategies: the full dose of blood thinners along with platelet transfusion or a reduced dose of blood thinners without platelet transfusion. The investigators will follow all patients for 90 days. If this pilot study is successful, it will help lead to a much larger trial, which will provide important information on the best treatment strategy in these patients.

Full description

The current proposal is for the pilot trial to assess feasibility of a full-scale RCT. To determine feasibility, the pilot and the full-scale trials will use the same recruitment strategy, inclusion/exclusion criteria, interventions, follow up duration, and measurement/adjudication of clinical outcomes. If the pilot trial finds that the full-scale trial is feasible, and no changes to the study design are indicated, the data from the pilot trial will be included in the full-scale trial, which will be efficient and reduce the recruitment time and costs of the full-scale trial.

The START trial is a multi-centre RCT with prospective, open-label, blind-evaluator (PROBE) design. Adult patients with acute cancer-associated thrombosis (diagnosed within 14 days) and thrombocytopenia (platelet count < 50,000/µL) secondary to cancer therapy or cancer itself will be randomized 1:1 to modified dose LMWH or higher dose LMWH with platelet transfusion support, to evaluate the superiority of a modified dose LMWH strategy in reducing clinically relevant bleeding events compared to full dose LMWH with platelet transfusion. The PROBE design is an efficient use of research funds while maintaining the benefits of randomization and blinded evaluation of endpoints.

Enrollment: 50 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adult patients (age ≥ 18) with active malignancy (malignancy diagnosed or treated within the previous 6 months, or progressive/relapsed);
2. Objectively confirmed VTE within last 14 days for which therapeutic anticoagulation is planned;
3. Thrombocytopenia with a platelet count < 50,000/uL from cancer therapy or malignancy itself;
4. Able to provide written informed consent

Exclusion criteria

1. Receipt of anticoagulant for index VTE with platelet count < 50,000/uL for > 72 hours;
2. Superficial vein thrombosis only;
3. Life expectancy < 1 month (as judged by the treating physicians);
4. Creatinine clearance < 30 ml/min;
5. Contraindication to LMWH such as a history of heparin induced thrombocytopenia;
6. Thrombocytopenia from other causes, such as thrombotic microangiopathy, immune thrombocytopenia, disseminated intravascular coagulation;
7. Previously documented history of refractoriness to platelet transfusion secondary to HLA antibodies;
8. Refusal of blood products;
9. Anticoagulation at any dose is deemed unsafe (i.e. active bleeding or bleeding disorders)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Modified dose LMWH without platelet transfusion support

Experimental group

Description:

Patients will be given modified dose LMWH as below based on the first platelet count of the day (daily in admitted patients or at least 2 times a week in outpatients), without empiric platelet transfusion: I. Platelet count 25-50,000/µL: 50% dose LMWH II. Platelet count \< 25,000/µL: hold anticoagulation

Treatment:

Biological: Tinzaparin

Biological: Enoxaparin

Biological: Dalteparin

Higher dose LMWH with platelet transfusion support

Active Comparator group

Description:

Patients assigned to higher dose LMWH (see below) will be given transfusion for 14 days when the first platelet count of the day falls below 50,000/uL (daily inpatient or at least 2 times a week in outpatients). Post-transfusion counts will not be routinely obtained unless clinically indicated I. Platelet count 25-50,000/µL: platelet transfusion + 100% dose LMWH II. Platelet count \< 25,000/µL: platelet transfusion + 50% dose LMWH After Day 14, patients will be transitioned to modified dose LMWH as the other arm without platelet transfusion. LMWH can include enoxaparin, dalteparin, or tinzaparin, with 100% as: * Enoxaparin - 1mg/kg subcutaneously twice daily * Dalteparin - 200 IU/kg subcutaneously daily for 1 month then 150 U/kg daily * Tinzaparin - 175 units/kg subcutaneously daily

Treatment:

Biological: Tinzaparin

Biological: Enoxaparin

Biological: Dalteparin