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Oral Apixaban (Eliquis) Versus Enoxaparin (Lovenox) for Thromboprophylaxis in Women With Suspected Pelvic Malignancy

Phase 2
Completed
Conditions
Gynecologic Cancer
Venous Thromboembolism
Interventions
Registration Number
NCT02366871
Lead Sponsor
University of Colorado, Denver
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
400
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.
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Oral apixabanOral apixabanOral apixaban 2.5 mg tablet twice daily for 28 days post-surgery
Subcutaneous enoxaparinSubcutaneous enoxaparinSubcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Incidence of Clinically Relevant Non Major Bleeding EventsDay 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.

Number of Participants With Incidence of Major BleedingDay 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.

Secondary Outcome Measures
NameTimeMethod
Number of Participants Who Met Medication Adherence RatesDay 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 AssessmentOn 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-opAt 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.

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.

Trial Locations

Locations (2)

University of Southern California Keck School of Medicine

🇺🇸

Los Angeles, California, United States

University of Colorado Denver

🇺🇸

Aurora, Colorado, United States

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