Upper Extremity Deep Vein Thrombosis, Central Venous Catheter Thrombosis, Cancer
Conditions
Keywords
Upper Extremity Deep Vein Thrombosis, Thromboprophylaxis, Cancer, Randomized Trial
Brief summary
Purpose of the Pilot Trial: To determine the feasibility of conducting a multicentre randomized open label controlled trial evaluating the use of prophylactic dose rivaroxaban to prevent central venous catheter (CVC) associated venous thromboembolism (VTE) among cancer patients. Hypothesis: treatment with low dose rivaroxaban (10mg) will reduce the incidence of upper extremity venous thrombosis in a high risk population with cancer and CVC.
Detailed description
Design: This is a pilot interventional study to be conducted at 2 Canadian Centres. The Ottawa Hospital and Juravinski Hospital. It is an open label randomized controlled trial. Consenting participants, meeting eligibility criteria will be randomized at the time of enrollment to one of two groups. Rivaroxaban 10mg by mouth daily x 90 (+/- 3) days OR Standard of Care Participants in the treatment arm will have study drug dispensed at Day 1 and take medication for 90 days or until CVC is removed. Follow up visits (in person or phone) will occur at Day 30 (+/- 3 days) and Day 90 (+/- 3 days). Overall, participants will be followed for 3 months. Adverse events will be collected for the first 90 days. Outcomes The primary feasibility outcome for the pilot study is the number of participants recruited per centre per month. We will obtain baseline details of the patient's type, location and treatment of cancer, comorbidities and medications. Secondary feasibility outcomes of the pilot study will include, consent rates, loss to follow up, adherence to therapy defining 80% or greater medication taken as having good adherence to study drug, proportion of screened patients who meet eligibility criteria.
Interventions
Rivaroxaban 10mg po daily x 90 (+/- 3 days)
Sponsors
Queen Elizabeth II Health Sciences Centre
University of Alberta
Hamilton Health Sciences Corporation
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Randomized Pilot Trial comparing two groups - Rivaroxaban 10mg po daily for 90 days vs standard of care (usual treatment)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Patients 18 years of age or older with a new or existing diagnosis of cancer with a CVC inserted within the last 72 hours.
Exclusion criteria
1. CVC in place for \>72 hours 2. Patient requires anticoagulation for other indication 3. Concomitant use of dual antiplatelet therapy 4. Prior VTE 5. Major bleeding event in the last 6 weeks 6. Patient on concomitant medication with known interaction with rivaroxaban (eg. CYP3A4 inhibitor) 7. Pregnancy (documentation of use of effective contraception if sexually active or negative B-Hcg required) 8. Known renal failure, based on Creatinine clearance \<30 mL/min (Cockcroft-Gault) (in the previous 3 months) 9. Documented severe liver disease (eg. acute clinical hepatitis, chronic active hepatitis, cirrhosis or ALT \>3ULN) ( in the previous 3 months) 10. Known thrombocytopenia \< 50x 109/L (in the previous 3 months) 11. Allergy to rivaroxaban 12. Life expectancy \<6 months 13. History of condition at increased bleeding risk including, but not limited to: 1. Major surgical procedure or trauma within 30 days before the randomization visit 2. Clinically significant gastrointestinal bleeding within 6 months before the randomization visit 3. History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding 4. Chronic hemorrhagic disorder 5. Known intracranial neoplasm, arteriovenous malformation, or aneurysm 6. Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg 14. Primary malignancy diagnosis of basal cell or squamous cell carcinoma of the skin or acute leukemia or myelodysplastic syndrome 15. Geographic inaccessibility 16. Refused or unable to obtain consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Feasibility Outcome - Number of Participants Recruited Per Month | 12 months | A convenience sample size of 100 patients was chosen to allow reporting of the average monthly recruitment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Feasibility Outcomes - Percentage of Participants With Good Adherence to Therapy | 90 days | Good adherence defined as 80% or greater study medication taken in patients randomized to receive Rivaroxaban thromboprophylaxis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Thrombotic Complication | 90 days | Thrombotic complication was defined as a combination of major venous thromboembolism (VTE); any symptomatic or incidentally detected proximal deep vein thrombosis (DVT) of the lower or upper limbs, any nonfatal symptomatic or incidental pulmonary embolism (PE), and pulmonary embolism-related death) and any other deep (ie, distal, splanchnic, or cerebral) or superficial venous thrombosis. |
| Number of Participants With CVC-Related Complication | 90 days | Central venous catheter (CVC) occlusion was defined as an obstruction of the CVC lumen that prevents or limits the ability to flush, withdraw blood, and/or administer solutions or medications |
| Number of Participants With Major Bleeding | 90 days | Defined by the International Society on Thrombosis and Haemostasis (ISTH) as overt bleeding associated with a decrease in the hemoglobin level of ≥2 g/dL, which led to transfusion of two or more units of packed red blood cells, occurred in a critical site, or contributed to death. |
| Number of Participants With Clinically Relevant Non-Major Bleed | 90 days | Clinically relevant non-major bleeding, as per the standardized definition by the ISTH, is any signs or symptoms of hemorrhage not meeting criteria for major bleeding but associated with medical intervention, unscheduled in-person contact with a healthcare professional or need for hospitalization or increased level of care. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban Thromboprophylaxis Rivaroxaban 10 mg po daily for 90 days(+/- 3 days). After the Day - 90 follow up, the study treatment will be discontinued and subsequent treatment will be at the discretion of the attending physician.
Rivaroxaban 10 MG: Rivaroxaban 10mg po daily x 90 (+/- 3 days) | 52 |
| Standard of Care No rivaroxaban prophylaxis. Management will be at the discretion of the attending physician. | 53 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 0 |
| Overall Study | Elective Surgery | 1 | 0 |
| Overall Study | End of chemotherapy removal of peripherally inserted central venous catheter | 5 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Rivaroxaban Thromboprophylaxis | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 11.9 | 61.6 years STANDARD_DEVIATION 12.7 | 60.8 years STANDARD_DEVIATION 12.3 |
| Cancer type Breast | 15 Participants | 14 Participants | 29 Participants |
| Cancer type Colorectal | 15 Participants | 16 Participants | 31 Participants |
| Cancer type Gynecological | 6 Participants | 5 Participants | 11 Participants |
| Cancer type Other | 8 Participants | 9 Participants | 17 Participants |
| Cancer type Pancreas | 3 Participants | 7 Participants | 10 Participants |
| Cancer type Stomach | 5 Participants | 2 Participants | 7 Participants |
| Central Venous Catheter Type PICC | 40 Participants | 42 Participants | 82 Participants |
| Central Venous Catheter Type Port-a-Cath | 12 Participants | 11 Participants | 23 Participants |
| Metastatic disease | 14 Participants | 19 Participants | 33 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 50 Participants | 49 Participants | 99 Participants |
| Sex: Female, Male Female | 36 Participants | 36 Participants | 72 Participants |
| Sex: Female, Male Male | 16 Participants | 17 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 53 |
| other Total, other adverse events | 16 / 52 | 12 / 53 |
| serious Total, serious adverse events | 11 / 52 | 10 / 53 |
Outcome results
Primary
Primary Feasibility Outcome - Number of Participants Recruited Per Month
A convenience sample size of 100 patients was chosen to allow reporting of the average monthly recruitment.
Time frame: 12 months
Population: Total number of participants enrolled per site over a 12 month recruitment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Site 1 | Primary Feasibility Outcome - Number of Participants Recruited Per Month | 7.5 Average enrolment rate/month/site |
| Site 2 | Primary Feasibility Outcome - Number of Participants Recruited Per Month | 2.0 Average enrolment rate/month/site |
Secondary
Secondary Feasibility Outcomes - Percentage of Participants With Good Adherence to Therapy
Good adherence defined as 80% or greater study medication taken in patients randomized to receive Rivaroxaban thromboprophylaxis.
Time frame: 90 days
Population: Data not collected for participants in the Standard of Care arm since they did not receive study medication and management was left to the discretion of the attending physician.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Site 1 | Secondary Feasibility Outcomes - Percentage of Participants With Good Adherence to Therapy | 96.7 percentage of participants |
Other Pre-specified
Number of Participants With Clinically Relevant Non-Major Bleed
Clinically relevant non-major bleeding, as per the standardized definition by the ISTH, is any signs or symptoms of hemorrhage not meeting criteria for major bleeding but associated with medical intervention, unscheduled in-person contact with a healthcare professional or need for hospitalization or increased level of care.
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Site 1 | Number of Participants With Clinically Relevant Non-Major Bleed | 2 Participants |
| Site 2 | Number of Participants With Clinically Relevant Non-Major Bleed | 2 Participants |
Other Pre-specified
Number of Participants With CVC-Related Complication
Central venous catheter (CVC) occlusion was defined as an obstruction of the CVC lumen that prevents or limits the ability to flush, withdraw blood, and/or administer solutions or medications
Time frame: 90 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Site 1 | Number of Participants With CVC-Related Complication | CVC positional occlusion | 0 Participants |
| Site 1 | Number of Participants With CVC-Related Complication | CVC migration | 0 Participants |
| Site 1 | Number of Participants With CVC-Related Complication | CVC occlusion | 0 Participants |
| Site 1 | Number of Participants With CVC-Related Complication | CVC-associated infection | 0 Participants |
| Site 2 | Number of Participants With CVC-Related Complication | CVC occlusion | 1 Participants |
| Site 2 | Number of Participants With CVC-Related Complication | CVC-associated infection | 2 Participants |
| Site 2 | Number of Participants With CVC-Related Complication | CVC migration | 1 Participants |
| Site 2 | Number of Participants With CVC-Related Complication | CVC positional occlusion | 1 Participants |
Other Pre-specified
Number of Participants With Major Bleeding
Defined by the International Society on Thrombosis and Haemostasis (ISTH) as overt bleeding associated with a decrease in the hemoglobin level of ≥2 g/dL, which led to transfusion of two or more units of packed red blood cells, occurred in a critical site, or contributed to death.
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Site 1 | Number of Participants With Major Bleeding | 1 Participants |
| Site 2 | Number of Participants With Major Bleeding | 0 Participants |
Other Pre-specified
Number of Participants With Thrombotic Complication
Thrombotic complication was defined as a combination of major venous thromboembolism (VTE); any symptomatic or incidentally detected proximal deep vein thrombosis (DVT) of the lower or upper limbs, any nonfatal symptomatic or incidental pulmonary embolism (PE), and pulmonary embolism-related death) and any other deep (ie, distal, splanchnic, or cerebral) or superficial venous thrombosis.
Time frame: 90 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Site 1 | Number of Participants With Thrombotic Complication | Major VTE - Upper extremity | 2 Participants |
| Site 1 | Number of Participants With Thrombotic Complication | Other thrombotic event - splanchnic vein thrombosis | 1 Participants |
| Site 1 | Number of Participants With Thrombotic Complication | Major VTE | 2 Participants |
| Site 1 | Number of Participants With Thrombotic Complication | Other thrombotic event - superficial vein thrombosis | 0 Participants |
| Site 1 | Number of Participants With Thrombotic Complication | Major VTE - PE | 0 Participants |
| Site 2 | Number of Participants With Thrombotic Complication | Other thrombotic event - superficial vein thrombosis | 1 Participants |
| Site 2 | Number of Participants With Thrombotic Complication | Major VTE | 3 Participants |
| Site 2 | Number of Participants With Thrombotic Complication | Major VTE - Upper extremity | 2 Participants |
| Site 2 | Number of Participants With Thrombotic Complication | Major VTE - PE | 1 Participants |
| Site 2 | Number of Participants With Thrombotic Complication | Other thrombotic event - splanchnic vein thrombosis | 1 Participants |