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

NCT ID: NCT02366871

Last Updated: 2020-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-28
• Study Completion Date: 2019-06-30

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.

Conditions

Gynecologic Cancer; Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Oral apixaban

Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery

Group Type: EXPERIMENTAL

Oral apixaban

Intervention Type: DRUG

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.

Subcutaneous enoxaparin

Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery.

Group Type: ACTIVE_COMPARATOR

Subcutaneous enoxaparin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Eliquis; Lovenox

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saketh Guntupalli, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Southern California Keck School of Medicine

Los Angeles, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32641236 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32589230 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

15-0187.cc

Identifier Type: -

Identifier Source: org_study_id