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

Обзор

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 2 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 30 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 for these patients.

Подробное описание

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.

Вмешательства

• Биопрепарат Enoxaparin
  I. Platelet count 25-50,000/µL: 0.5mg/kg subcutaneously twice daily II. Platelet count \< 25,000/µL: hold anticoagulation
• Биопрепарат Dalteparin
  I. Platelet count 25-50,000/µL: 100 IU/kg subcutaneously daily for the first month of an acute VTE then 75 U/kg II. Platelet count \< 25,000/µL: hold anticoagulation
• Биопрепарат Tinzaparin
  I. Platelet count 25-50,000/µL: 87.5 units/kg subcutaneously daily II. Platelet count \< 25,000/µL: hold anticoagulation

Первичные конечные точки

• Feasibility - The average number of patients recruited per month [Срок оценки: 18 months]

Вторичные конечные точки (12)

• Feasibility - Proportion of eligible patients who provide consent [Срок оценки: 18 months]
• Feasibility - Reasons for non-participation in eligible patients [Срок оценки: 18 months]
• Feasibility - Number of patients who complete study procedures by adhering to protocol [Срок оценки: 18 months]
• Feasibility - Rates of withdrawal [Срок оценки: 18 months]
• Feasibility - Loss to follow-up [Срок оценки: 18 months]
• Feasibility - Crossover between treatment arms [Срок оценки: 18 months]
• Clinical Outcome - Rate of clinically relevant bleeding (composite of major bleeding and clinically relevant non-major bleeding events) [Срок оценки: 18 months]
• Clinical Outcome - Rate of symptomatic or incidentally detected recurrent or new major VTE [Срок оценки: 18 months]
• Clinical Outcome - PE-related death [Срок оценки: 18 months]
• Clinical Outcome - Composite of recurrent VTE and major bleeding events [Срок оценки: 18 months]
• Clinical Outcome - Non-major VTE (distal upper or lower extremity DVT, superficial upper or lower extremity vein thrombosis) [Срок оценки: 18 months]
• Clinical Outcome - Duration of thrombocytopenia (days of platelet count < 50,000/uL) per patient [Срок оценки: 18 months]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 4 центра

• University of Alberta — Edmonton
• The Ottawa Hospital — Ottawa
• Niagara Health - St. Catharines Site — Saint Catharines
• Windsor Regional Hospital — Windsor

Идентификаторы

NCT: NCT05255003 · START Pilot

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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