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

Primary Purpose

Cancer-associated Thrombosis, Thrombocytopenia

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Enoxaparin
Dalteparin
Tinzaparin
Sponsored by
Ottawa Hospital Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer-associated Thrombosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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 30 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. Life expectancy < 3 months (as judged by the treating physicians);
  3. Creatinine clearance < 30 ml/min;
  4. Contraindication to LMWH such as a history of heparin induced thrombocytopenia;
  5. Thrombocytopenia from other causes, such as thrombotic microangiopathy, immune thrombocytopenia, disseminated intravascular coagulation;
  6. Previously documented history of refractoriness to platelet transfusion secondary to HLA antibodies;
  7. Refusal of blood products;
  8. Anticoagulation at any dose is deemed unsafe (i.e. active bleeding or bleeding disorders)

Sites / Locations

  • The Ottawa HospitalRecruiting
  • Windsor Regional HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Modified dose LMWH without platelet transfusion support

Higher dose LMWH with platelet transfusion support

Arm 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

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

Outcomes

Primary Outcome Measures

Feasibility - The average number of patients recruited per month
The average number of patients recruited per month

Secondary Outcome Measures

Feasibility - Proportion of eligible patients who provide consent
Number of consenting participants from the number of eligible patients
Feasibility - Reasons for non-participation in eligible patients
Reasons for non-participation in eligible patients
Feasibility - Number of patients who complete study procedures by adhering to protocol
Number of participants adhering to the protocol (such as anticoagulation, transfusion, platelet count monitoring according to the protocol)
Feasibility - Rates of withdrawal
Number of participants withdrawing from study
Feasibility - Loss to follow-up
Number of participants lost to follow-up
Feasibility - Crossover between treatment arms
Number of participants crossing over between treatment arms
Clinical Outcome - Rate of clinically relevant bleeding (composite of major bleeding and clinically relevant non-major bleeding events)
Rate of clinically relevant bleeding (composite of major bleeding and clinically relevant non-major bleeding events)
Clinical Outcome - Rate of symptomatic or incidentally detected recurrent or new major VTE
Rate of symptomatic or incidentally detected recurrent or new major VTE
Clinical Outcome - PE-related death
PE-related death
Clinical Outcome - Composite of recurrent VTE and major bleeding events
Composite of recurrent VTE and major bleeding events
Clinical Outcome - Non-major VTE (distal upper or lower extremity DVT, superficial upper or lower extremity vein thrombosis)
Number of non-major VTE (distal upper or lower extremity DVT, superficial upper or lower extremity vein thrombosis)
Clinical Outcome - Duration of thrombocytopenia (days of platelet count < 50,000/uL) per patient
Duration of thrombocytopenia (days of platelet count < 50,000/uL) per patient
Clinical Outcome - Number of transfused units and adverse platelet transfusion reactions
Number of transfused units and adverse platelet transfusion reactions
Clinical Outcome - Overall mortality
Overall mortality
Clinical Outcome - Health-related quality of life using EuroQoL-EQ-5D-5L questionnaire
Health-related quality of life using EuroQoL-EQ-5D-5L questionnaire

Full Information

First Posted
February 6, 2022
Last Updated
May 30, 2023
Sponsor
Ottawa Hospital Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05255003
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 29, 2022 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer-associated Thrombosis, Thrombocytopenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Modified dose LMWH without platelet transfusion support
Arm Type
Experimental
Arm 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
Arm Title
Higher dose LMWH with platelet transfusion support
Arm Type
Active Comparator
Arm 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
Intervention Type
Biological
Intervention Name(s)
Enoxaparin
Other Intervention Name(s)
Lovenox
Intervention Description
I. Platelet count 25-50,000/µL: 0.5mg/kg subcutaneously twice daily II. Platelet count < 25,000/µL: hold anticoagulation
Intervention Type
Biological
Intervention Name(s)
Dalteparin
Other Intervention Name(s)
Fragmin
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Tinzaparin
Other Intervention Name(s)
Innohep
Intervention Description
I. Platelet count 25-50,000/µL: 87.5 units/kg subcutaneously daily II. Platelet count < 25,000/µL: hold anticoagulation
Primary Outcome Measure Information:
Title
Feasibility - The average number of patients recruited per month
Description
The average number of patients recruited per month
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Feasibility - Proportion of eligible patients who provide consent
Description
Number of consenting participants from the number of eligible patients
Time Frame
18 months
Title
Feasibility - Reasons for non-participation in eligible patients
Description
Reasons for non-participation in eligible patients
Time Frame
18 months
Title
Feasibility - Number of patients who complete study procedures by adhering to protocol
Description
Number of participants adhering to the protocol (such as anticoagulation, transfusion, platelet count monitoring according to the protocol)
Time Frame
18 months
Title
Feasibility - Rates of withdrawal
Description
Number of participants withdrawing from study
Time Frame
18 months
Title
Feasibility - Loss to follow-up
Description
Number of participants lost to follow-up
Time Frame
18 months
Title
Feasibility - Crossover between treatment arms
Description
Number of participants crossing over between treatment arms
Time Frame
18 months
Title
Clinical Outcome - Rate of clinically relevant bleeding (composite of major bleeding and clinically relevant non-major bleeding events)
Description
Rate of clinically relevant bleeding (composite of major bleeding and clinically relevant non-major bleeding events)
Time Frame
18 months
Title
Clinical Outcome - Rate of symptomatic or incidentally detected recurrent or new major VTE
Description
Rate of symptomatic or incidentally detected recurrent or new major VTE
Time Frame
18 months
Title
Clinical Outcome - PE-related death
Description
PE-related death
Time Frame
18 months
Title
Clinical Outcome - Composite of recurrent VTE and major bleeding events
Description
Composite of recurrent VTE and major bleeding events
Time Frame
18 months
Title
Clinical Outcome - Non-major VTE (distal upper or lower extremity DVT, superficial upper or lower extremity vein thrombosis)
Description
Number of non-major VTE (distal upper or lower extremity DVT, superficial upper or lower extremity vein thrombosis)
Time Frame
18 months
Title
Clinical Outcome - Duration of thrombocytopenia (days of platelet count < 50,000/uL) per patient
Description
Duration of thrombocytopenia (days of platelet count < 50,000/uL) per patient
Time Frame
18 months
Title
Clinical Outcome - Number of transfused units and adverse platelet transfusion reactions
Description
Number of transfused units and adverse platelet transfusion reactions
Time Frame
18 months
Title
Clinical Outcome - Overall mortality
Description
Overall mortality
Time Frame
18 months
Title
Clinical Outcome - Health-related quality of life using EuroQoL-EQ-5D-5L questionnaire
Description
Health-related quality of life using EuroQoL-EQ-5D-5L questionnaire
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer Brinkhurst
Phone
+16137378899
Ext
71068
Email
jbrinkhurst@ohri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tzu-Fei Wang, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marc Carrier, MD
Organizational Affiliation
Ottawa Hospital Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Multicentre Trial Coordinator
Phone
6137378899
Ext
71068
Email
jbrinkhurst@ohri.ca
First Name & Middle Initial & Last Name & Degree
Tzu-Fei Wang, MD
Facility Name
Windsor Regional Hospital
City
Windsor
State/Province
Ontario
ZIP/Postal Code
N8W 1L9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Cervi, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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