Venous Thormboembolism
Conditions
Brief summary
Hospitalized patients with histologically or cytologically confirmed diagnosis of solid tumor malignancy, lymphoma, or multiple myeloma and who are at high risk for a venous thromboembolism will be randomized to standard dose versus intermediate dose enoxaparin.
Detailed description
In a phase II trial, high risk hospitalized cancer patients will be enrolled and randomized to standard dose enoxaparin versus intermediate dose (weight adjusted) enoxaparin thromboprophylaxis. Study subjects will be administered enoxaparin during hospitalization in a double-blinded manner. Following completion of 14 days, the study arms will be unblinded and lower extremity ultrasound performed on the standard dose enoxaparin arm in order to more accurately determine the overall cumulative incidence of thrombosis in this group.
Interventions
DRUGEnoxaparin
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have histologically or cytologically confirmed diagnosis of solid tumor malignancy, lymphoma or multiple myeloma. * Cancer diagnosis or received treatment (chemotherapy or radiotherapy) for malignancy within the previous 6 months * One or more Padua-based risk factor: * History of previous venous thromboembolic event (excluding superficial vein thrombosis) * Reduced mobility (ECOG performance status 3 or 4, see Appendix A) * Established hereditary thrombophilia (e.g. Factor V Leiden, G20210 prothrombin mutation, protein C or S deficiency, antithrombin deficiency). * Recent surgery within the last 30 days * Age ≥ 70 years * Congestive heart failure (NYHA class III or IV) * Complicated respiratory insufficiency (defined as an increased requirement for supplementary oxygen of at least 2L) * Acute myocardial infarction or ischemic stroke * Obesity (BMI ≥ 30) * Receiving hormonal agents (e.g. tamoxifen, estrogen, testosterone) * Acute infection (i.e. requiring antimicrobial therapy) * Age ≥ 18 years * Life expectancy of greater than 30 days * Platelet count ≥ 100,000/mcL * Creatinine \< 1.5 mg/dL or estimated creatinine clearance ≥ 50 mL/min/1.73 m2 * Ability to understand and the willingness to sign a written informed consent document * Weight between 50kg to 130 kg.
Exclusion criteria
* History of allergic reactions attributed to heparin or low molecular weight heparin * Active bleeding or otherwise considered high risk for hemorrhage (e.g. known acute gastrointestinal ulcer) * Any history of significant hemorrhage (requiring hospitalization or transfusion) within the last 6 months (excluding hemorrhage during operative procedure). * History of heparin induced Thrombocytopenia * Presence of coagulopathy (PT or PTT\> 1.2 x upper limit of normal) * Known diagnosis of disseminated intravascular coagulation * Currently receiving therapeutic anticoagulant therapy or dual antiplatelet therapy (eg. aspirin and clopidogrel) * Uncontrolled arterial hypertension (systolic blood pressure \> 200mmHg, diastolic \>110mmHg) * Active peptic ulcer disease * Bacterial Endocardititis * Received any type of Pharmacologic Thromboprophylaxis (e.g. low molecular weight heparin or heparin) for \>48 hours during current hospitalization * Known brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Venous Thromboembolic Events (VTE) in Standard Dose Enoxaparin Arm at 17 Days | 17 days only measured in Arm A (Standard dose enoxaparin) | To investigate the numbers of VTE in hospitalized cancer patients receiving standard dose |
| Number Participants With Major Hemorrhage | 14 days | Number of major hemorrhage in weight-adjusted enoxaparin arm and standard-dose enoxaparin arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Symptomatic Venous Thromboembolic Events (VTE) | 14 days | Comparing number of symptomatic VTE (data collected prior to unblinding) for the standard dose (Arm A) versus intermediate dose enoxaparin (Arm B). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A: Standard Dose Enoxaparin Participants will receive Enoxaparin 40 mg subcutaneously once daily. On study Enoxaparin will be administered for up 14 days during hospitalization.
After the day 14 assessment, treatment arms will be un-blinded in order to appropriately schedule a bilateral lower extremity ultrasound for participants enrolled onto Arm A at day 17.
Enoxaparin | 25 |
| B: Weight Adjusted Enoxaparin Participants will receive Enoxaparin at 1mg/kg subcutaneously once daily with maximum dose of 100 mg daily. Participants who weigh more than 100kg will be capped at 100mg.
On study Enoxaparin will be administered for up 14 days during hospitalization.
Enoxaparin | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | A: Standard Dose Enoxaparin | B: Weight Adjusted Enoxaparin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 16 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 19 Participants | 18 Participants | 37 Participants |
| Region of Enrollment United States | 23 Participants | 24 Participants | 47 Participants |
| Sex: Female, Male Female | 19 Participants | 11 Participants | 30 Participants |
| Sex: Female, Male Male | 4 Participants | 13 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 10 / 23 | 6 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 |
Outcome results
Primary
Number Participants With Major Hemorrhage
Number of major hemorrhage in weight-adjusted enoxaparin arm and standard-dose enoxaparin arm
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: Standard Dose Enoxaparin | Number Participants With Major Hemorrhage | 1 Participants |
| B: Weight Adjusted Enoxaparin | Number Participants With Major Hemorrhage | 0 Participants |
Primary
Total Number of Venous Thromboembolic Events (VTE) in Standard Dose Enoxaparin Arm at 17 Days
To investigate the numbers of VTE in hospitalized cancer patients receiving standard dose
Time frame: 17 days only measured in Arm A (Standard dose enoxaparin)
Population: All patients who were randomized to the standard dose of enoxaparin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A: Standard Dose Enoxaparin | Total Number of Venous Thromboembolic Events (VTE) in Standard Dose Enoxaparin Arm at 17 Days | 2 participants |
Secondary
Number of Symptomatic Venous Thromboembolic Events (VTE)
Comparing number of symptomatic VTE (data collected prior to unblinding) for the standard dose (Arm A) versus intermediate dose enoxaparin (Arm B).
Time frame: 14 days
Population: The analysis data set is comprised of evaluated patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A: Standard Dose Enoxaparin | Number of Symptomatic Venous Thromboembolic Events (VTE) | 0 Participants |
| B: Weight Adjusted Enoxaparin | Number of Symptomatic Venous Thromboembolic Events (VTE) | 0 Participants |