Clinical trial NCT05255003: STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
Official title: STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cancer-associated Thrombosis
Thrombocytopenia
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2022-02-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Feasibility - The average number of patients recruited per month
timeFrame: 18 months
Secondary outcomes:
measure: Feasibility - Proportion of eligible patients who provide consent
timeFrame: 18 months
measure: Feasibility - Reasons for non-participation in eligible patients
timeFrame: 18 months
measure: Feasibility - Number of patients who complete study procedures by adhering to protocol
timeFrame: 18 months
measure: Feasibility - Rates of withdrawal
timeFrame: 18 months
measure: Feasibility - Loss to follow-up
timeFrame: 18 months
measure: Feasibility - Crossover between treatment arms
timeFrame: 18 months
measure: Clinical Outcome - Rate of clinically relevant bleeding (composite of major bleeding and clinically relevant non-major bleeding events)
timeFrame: 18 months
measure: Clinical Outcome - Rate of symptomatic or incidentally detected recurrent or new major VTE
timeFrame: 18 months
measure: Clinical Outcome - PE-related death
timeFrame: 18 months
measure: Clinical Outcome - Composite of recurrent VTE and major bleeding events
timeFrame: 18 months
measure: Clinical Outcome - Non-major VTE (distal upper or lower extremity DVT, superficial upper or lower extremity vein thrombosis)
timeFrame: 18 months
measure: Clinical Outcome - Duration of thrombocytopenia (days of platelet count < 50,000/uL) per patient
timeFrame: 18 months
measure: Clinical Outcome - Number of transfused units and adverse platelet transfusion reactions
timeFrame: 18 months
measure: Clinical Outcome - Overall mortality
timeFrame: 18 months
measure: Clinical Outcome - Health-related quality of life using EuroQoL-EQ-5D-5L questionnaire
timeFrame: 18 months
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hospital
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Tzu-Fei Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Hospital Research Institute
name: Marc Carrier, MD
role: PRINCIPAL_INVESTIGATOR
References: