Gynecologic Cancer, Venous Thromboembolism
Conditions
Brief summary
The study will evaluate the incidence of major bleeding (including clinically relevant non-major (CRNM) bleeding) events in women undergoing surgery for gynecologic cancer with apixaban 2.5 mg twice a day (BID) compared to current standard of care, subcutaneous enoxaparin 40 mg once a day (QD) for 28 days post surgery.
Detailed description
Apixaban (Eliquis) is an oral anticoagulant for the treatment and prevention of thromboembolic events. It is advantageous as there is no need to perform routine blood monitoring tests including, international normalized ratio (INR), partial thromboplastin time (PTT) and Factor Xa, to determine clotting in participants receiving treatment. Several studies have shown the efficacy of apixaban for the treatment and prevention of a venous thromboembolism (VTE). We anticipate that the same efficacy could be replicated in the prevention of VTE in women undergoing surgery for gynecologic cancer. An oral-anticoagulant for standard treatment for prevention of VTE outcomes following surgery could help improve the surgical mortalities associated with gynecologic oncology surgical patients, improve patient adherence for outpatient treatment, and reduce VTE surveillance and outcomes.
Interventions
DRUGOral apixaban
To evaluate the incidence of major bleeding (including CRNM bleeding) events in women undergoing surgery for gynecologic cancer with apixaban 2.5 mg BID compared to current standard of care, subcutaneous enoxaparin 40 mg QD for 28 days post surgery.
To evaluate the incidence of major bleeding (including CRNM bleeding) events in women undergoing surgery for gynecologic cancer with apixaban 2.5 mg BID compared to current standard of care, subcutaneous enoxaparin 40 mg QD for 28 days post surgery.
Sponsors
Bristol-Myers Squibb
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Suitable candidate for surgery (meets appropriate performance status, no significant cardiac/renal/hepatic dysfunction * Diagnosis of pelvic malignancy (suspected/confirmed ovarian, endometrial/uterine, cervical cancers, and vulvar cancers) undergoing surgical debulking, * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to surgery, * Women must not be breastfeeding, WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) apixaban plus 5 half-lives of study drug apixaban (2.5 days) plus 30 days (duration of ovulatory cycle) for a total of 32.5 days post-treatment completion.
Exclusion criteria
* Malignancy or mass that is non-gynecologic in origin (mass/tumor of origin other than reproductive organ such as rectal, abdominal, breast) * Positive pregnancy test on day of surgery, * Known history of Venous (Thromboembolism) VTE prior to diagnosis (DVT or Pulmonary Embolism (PE)) due to increased underlying risk of new event * Concomitant NSAIDS or other anticoagulant/antiplatelet therapy including Acetylsalicylic Acid (Aspirin) (ASA) \>81mg/day, * Selective serotonin re uptake inhibitor (SSRIs) and Serotonin-nor-epinephrine re uptake inhibitor (SNRIs) (common anti-depressant therapies), * Uncontrolled severe hypertension (systolic \>200 mmHg or diastolic \>120 mmHg), * With prosthetic heart valves, * Active bleeding condition (not limited to: thrombocytopenia, haemophilias, potential bleeding lesions, recent trauma or surgery, recent stroke, confirmed intracranial or intraspinal bleeding), * Known or documented bleeding disorders not limited to: anti-phospholipid syndrome, homozygotes for Factor V Leiden deficiency, antithrombin III deficiency, protein C deficiency, Protein S deficiency, hyperhomocysteinemia, systemic lupus erythematous, or Prothrombin G2020 gene mutation, * Significant renal disease as defined by creatinine clearance less than 30 mL/min, * Significant liver disease as defined as Aspartate Transaminase (AST) or Alanine Transaminase (ALT) twice than normal, * Concomitant use of dual strong inhibitors or inducers (CYP3A4, P-gp) * Protein C deficiency (increased risk of skin necrosis do those on injectable anticoagulation), * Documented allergy to apixaban and/or enoxaparin, * Patient's deemed otherwise clinically unfit for clinical trial per Investigator's discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incidence of Major Bleeding | Day 1 post-op/standard of care first medication dose to day 90 (+/-14 days) post-op/standard of care | The International Society on Thrombosis and Hemostasis criteria (ISTH) will be used to assess incidence of major bleeding. Participants were monitored for up to 90 days. This is the number of participants who have had at least one major bleeding incidence during the time of observation. |
| Number of Participants With Incidence of Clinically Relevant Non Major Bleeding Events | Day 1 post-op/standard of care first dose of medication to day 90 (+/- 14 days) post-op/standard of care | Participants were monitored for up to 90 days. This is the number of participants with bleeding events that did not meet the ISTH criteria but still required intervention. This is the number of participants who had at least one non-major bleeding event during the time of observation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incidence of Venous Thromboembolism (VTEs): Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) | Day 1 post-op/standard of care to day first dose of medication 90 (+/- 14 days) post-op/standard of care | Participants were monitored for up to 90 days. Both DVTs and PEs will be measured using the Wells criteria, ultrasound, and/or CT. This is the number of participants who had at least one DVT or PE during the time of observation. |
| Number of Participants Who Met Medication Adherence Rates | Day 1 post-op/standard of care first dose of medication to Day 28 (+/- 4 days) post-op/standard of care | Participants were monitored for up to 28 days. This was measured through self-report, patient diaries, and the return of all medication bottles/syringes. This was the number of participants that did not miss more than 2 days of study medication over 28 days (less than 4 pills or 2 injections missed). |
| Number of Participants With a Patient Satisfaction Assessment | On visit 4, which is 28 days (+/- 4 days) post-op/standard of care | Participants were monitored at the 28 (+/- 4) day post-op visit. This was measured through administering a participant satisfaction questionnaire ranging from strongly agree to strongly disagree.This is the number of participants that completed the questionnaire in response to agreeing it was difficult to remember to take the medication, agreeing that there was pain associated with the medication, and agreeing that the medication was easy to use. |
| Change in Quality of Life From Baseline to 28 Days Post-op | At baseline, and visit 4, which is 28 days (+/- 4 days) post-op/standard of care | This was measured through a validated health survey (SF-8™) provided by a healthcare company (Optum®), which measured overall physical and mental well-being, with responses ranging from none to very, not at all to extremely, etc. Change was calculated as the difference at baseline versus 28 days post op. The score was 0-100 and a higher score was considered a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Apixaban Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery
Oral apixaban: To evaluate the incidence of major bleeding (including CRNM bleeding) events in women undergoing surgery for gynecologic cancer with apixaban 2.5 mg BID compared to current standard of care, subcutaneous enoxaparin 40 mg QD for 28 days post surgery. | 204 |
| Subcutaneous Enoxaparin Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery.
Subcutaneous enoxaparin: To evaluate the incidence of major bleeding (including CRNM bleeding) events in women undergoing surgery for gynecologic cancer with apixaban 2.5 mg BID compared to current standard of care, subcutaneous enoxaparin 40 mg QD for 28 days post surgery. | 196 |
| Total | 400 |
Baseline characteristics
| Characteristic | Total | Oral Apixaban | Subcutaneous Enoxaparin |
|---|---|---|---|
| Age, Continuous | 58.0 years | 58.0 years | 58.5 years |
| Body-mass index | 27.0 kg/m^2 | 27.4 kg/m^2 | 26.5 kg/m^2 |
| Confirm Origin Benign | 77 Participants | 40 Participants | 37 Participants |
| Confirm Origin Cervical Cancer | 30 Participants | 12 Participants | 18 Participants |
| Confirm Origin Other | 11 Participants | 4 Participants | 7 Participants |
| Confirm Origin Ovarian/Fallopian Cancer | 141 Participants | 77 Participants | 64 Participants |
| Confirm Origin Uterine Cancer | 128 Participants | 65 Participants | 63 Participants |
| Confirm Origin Vulva/Vaginal Cancer | 13 Participants | 6 Participants | 7 Participants |
| Length of Surgery | 209 minutes | 204 minutes | 215.5 minutes |
| Race/Ethnicity, Customized Race/ethnic group African American | 11 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Race/ethnic group Asian | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race/ethnic group Hispanic | 61 Participants | 38 Participants | 23 Participants |
| Race/Ethnicity, Customized Race/ethnic group White Non-Hispanic | 322 Participants | 158 Participants | 164 Participants |
| Sex: Female, Male Female | 400 Participants | 204 Participants | 196 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Stage Benign | 77 Participants | 40 Participants | 37 Participants |
| Stage High stage (III/IV) | 158 Participants | 84 Participants | 74 Participants |
| Stage Low stage (I/II) | 165 Participants | 80 Participants | 85 Participants |
| Surgeries Bilateral/uni salpingo-oophorectomy(BSO)/USO | 91 Participants | 42 Participants | 49 Participants |
| Surgeries Bowel Resection | 37 Participants | 25 Participants | 12 Participants |
| Surgeries Lymph Node Dissection | 181 Participants | 93 Participants | 88 Participants |
| Surgeries Radical Hysterectomy | 42 Participants | 18 Participants | 24 Participants |
| Surgeries Removal of Omentum | 164 Participants | 82 Participants | 82 Participants |
| Surgeries Surgical Complication | 25 Participants | 15 Participants | 10 Participants |
| Surgeries total abdominal hysterectomy(TAH) with BSO/USO | 228 Participants | 116 Participants | 112 Participants |
| Surgeries total abdominal hysterectomy (w/out ovaries) | 8 Participants | 5 Participants | 3 Participants |
| Surgical Intervention Minimally Invasive | 83 Participants | 39 Participants | 44 Participants |
| Surgical Intervention Open | 317 Participants | 165 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 204 | 2 / 196 |
| other Total, other adverse events | 53 / 204 | 45 / 196 |
| serious Total, serious adverse events | 13 / 204 | 14 / 196 |
Outcome results
Primary
Number of Participants With Incidence of Clinically Relevant Non Major Bleeding Events
Participants were monitored for up to 90 days. This is the number of participants with bleeding events that did not meet the ISTH criteria but still required intervention. This is the number of participants who had at least one non-major bleeding event during the time of observation.
Time frame: Day 1 post-op/standard of care first dose of medication to day 90 (+/- 14 days) post-op/standard of care
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Apixaban | Number of Participants With Incidence of Clinically Relevant Non Major Bleeding Events | 12 Participants |
| Subcutaneous Enoxaparin | Number of Participants With Incidence of Clinically Relevant Non Major Bleeding Events | 19 Participants |
Primary
Number of Participants With Incidence of Major Bleeding
The International Society on Thrombosis and Hemostasis criteria (ISTH) will be used to assess incidence of major bleeding. Participants were monitored for up to 90 days. This is the number of participants who have had at least one major bleeding incidence during the time of observation.
Time frame: Day 1 post-op/standard of care first medication dose to day 90 (+/-14 days) post-op/standard of care
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Apixaban | Number of Participants With Incidence of Major Bleeding | 1 Participants |
| Subcutaneous Enoxaparin | Number of Participants With Incidence of Major Bleeding | 1 Participants |
Secondary
Change in Quality of Life From Baseline to 28 Days Post-op
This was measured through a validated health survey (SF-8™) provided by a healthcare company (Optum®), which measured overall physical and mental well-being, with responses ranging from none to very, not at all to extremely, etc. Change was calculated as the difference at baseline versus 28 days post op. The score was 0-100 and a higher score was considered a better outcome.
Time frame: At baseline, and visit 4, which is 28 days (+/- 4 days) post-op/standard of care
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oral Apixaban | Change in Quality of Life From Baseline to 28 Days Post-op | physical score-baseline | 50.7 score on a scale |
| Oral Apixaban | Change in Quality of Life From Baseline to 28 Days Post-op | physical score-visit 4 | 39.2 score on a scale |
| Oral Apixaban | Change in Quality of Life From Baseline to 28 Days Post-op | Physical change | -5.9 score on a scale |
| Oral Apixaban | Change in Quality of Life From Baseline to 28 Days Post-op | mental score-baseline | 50.7 score on a scale |
| Oral Apixaban | Change in Quality of Life From Baseline to 28 Days Post-op | mental score-visit 4 | 50.7 score on a scale |
| Oral Apixaban | Change in Quality of Life From Baseline to 28 Days Post-op | Mental change | 0.8 score on a scale |
| Subcutaneous Enoxaparin | Change in Quality of Life From Baseline to 28 Days Post-op | mental score-visit 4 | 49.3 score on a scale |
| Subcutaneous Enoxaparin | Change in Quality of Life From Baseline to 28 Days Post-op | physical score-baseline | 49.7 score on a scale |
| Subcutaneous Enoxaparin | Change in Quality of Life From Baseline to 28 Days Post-op | mental score-baseline | 49.7 score on a scale |
| Subcutaneous Enoxaparin | Change in Quality of Life From Baseline to 28 Days Post-op | physical score-visit 4 | 38.5 score on a scale |
| Subcutaneous Enoxaparin | Change in Quality of Life From Baseline to 28 Days Post-op | Mental change | 0.0 score on a scale |
| Subcutaneous Enoxaparin | Change in Quality of Life From Baseline to 28 Days Post-op | Physical change | -6.2 score on a scale |
Secondary
Number of Participants Who Met Medication Adherence Rates
Participants were monitored for up to 28 days. This was measured through self-report, patient diaries, and the return of all medication bottles/syringes. This was the number of participants that did not miss more than 2 days of study medication over 28 days (less than 4 pills or 2 injections missed).
Time frame: Day 1 post-op/standard of care first dose of medication to Day 28 (+/- 4 days) post-op/standard of care
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Apixaban | Number of Participants Who Met Medication Adherence Rates | 173 Participants |
| Subcutaneous Enoxaparin | Number of Participants Who Met Medication Adherence Rates | 164 Participants |
Secondary
Number of Participants With a Patient Satisfaction Assessment
Participants were monitored at the 28 (+/- 4) day post-op visit. This was measured through administering a participant satisfaction questionnaire ranging from strongly agree to strongly disagree.This is the number of participants that completed the questionnaire in response to agreeing it was difficult to remember to take the medication, agreeing that there was pain associated with the medication, and agreeing that the medication was easy to use.
Time frame: On visit 4, which is 28 days (+/- 4 days) post-op/standard of care
Population: One patient did not answer the pain associated with taking the medication category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Difficult remembering to take medication | Agree | 23 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Difficult remembering to take medication | Neutral | 16 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Difficult remembering to take medication | Disagree | 149 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Pain associated with taking the medication | Agree | 4 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Pain associated with taking the medication | Neutral | 10 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Pain associated with taking the medication | Disagree | 173 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Was medication easy to take | Agree | 186 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Was medication easy to take | Neutral | 2 Participants |
| Oral Apixaban | Number of Participants With a Patient Satisfaction Assessment | Was medication easy to take | Disagree | 0 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Was medication easy to take | Neutral | 21 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Difficult remembering to take medication | Agree | 23 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Pain associated with taking the medication | Disagree | 70 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Difficult remembering to take medication | Neutral | 15 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Difficult remembering to take medication | Disagree | 149 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Was medication easy to take | Agree | 110 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Pain associated with taking the medication | Agree | 92 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Was medication easy to take | Disagree | 56 Participants |
| Subcutaneous Enoxaparin | Number of Participants With a Patient Satisfaction Assessment | Pain associated with taking the medication | Neutral | 25 Participants |
Secondary
Number of Participants With Incidence of Venous Thromboembolism (VTEs): Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
Participants were monitored for up to 90 days. Both DVTs and PEs will be measured using the Wells criteria, ultrasound, and/or CT. This is the number of participants who had at least one DVT or PE during the time of observation.
Time frame: Day 1 post-op/standard of care to day first dose of medication 90 (+/- 14 days) post-op/standard of care
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Apixaban | Number of Participants With Incidence of Venous Thromboembolism (VTEs): Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) | 2 Participants |
| Subcutaneous Enoxaparin | Number of Participants With Incidence of Venous Thromboembolism (VTEs): Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) | 3 Participants |