Clinical trial NCT02366871: Oral Apixaban (Eliquis) Versus Enoxaparin (Lovenox) for Thromboprophylaxis in Women With Suspected Pelvic Malignancy
Official title: The Safety of Oral Apixaban (Eliquis) Versus Subcutaneous Enoxaparin (Lovenox) for Thromboprophylaxis in Women With Suspected Pelvic Malignancy; a Prospective Randomized Open Blinded End-point (PROBE) Design
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gynecologic Cancer
Venous Thromboembolism
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2015-02-19
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Incidence of Major Bleeding
timeFrame: Day 1 post-op/standard of care first medication dose to day 90 (+/-14 days) post-op/standard of care
measure: Number of Participants With Incidence of Clinically Relevant Non Major Bleeding Events
timeFrame: Day 1 post-op/standard of care first dose of medication to day 90 (+/- 14 days) post-op/standard of care
Secondary outcomes:
measure: Number of Participants With Incidence of Venous Thromboembolism (VTEs): Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
timeFrame: Day 1 post-op/standard of care to day first dose of medication 90 (+/- 14 days) post-op/standard of care
measure: Number of Participants Who Met Medication Adherence Rates
timeFrame: Day 1 post-op/standard of care first dose of medication to Day 28 (+/- 4 days) post-op/standard of care
measure: Number of Participants With a Patient Satisfaction Assessment
timeFrame: On visit 4, which is 28 days (+/- 4 days) post-op/standard of care
measure: Change in Quality of Life From Baseline to 28 Days Post-op
timeFrame: At baseline, and visit 4, which is 28 days (+/- 4 days) post-op/standard of care
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Keck School of Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Saketh Guntupalli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ross ME, Glickman A, Brennecke A, Tayebnejad A, Guntupalli SR. Adherence to postoperative thromboprophylactic medication among gynecologic oncology patients: A subanalysis. Gynecol Oncol. 2020 Sep;158(3):754-759. doi: 10.1016/j.ygyno.2020.06.505. Epub 2020 Jul 6.
citation: Guntupalli SR, Brennecke A, Behbakht K, Tayebnejad A, Breed CA, Babayan LM, Cheng G, Ramzan AA, Wheeler LJ, Corr BR, Lefkowits C, Sheeder J, Matsuo K, Flink D. Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e207410. doi: 10.1001/jamanetworkopen.2020.7410.