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

NCT02366871 | Completed Phase 2 Results DMC

• 1 other identifier: 15-0187.cc
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 2

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.

Conditions

Gynecologic Cancer; Venous Thromboembolism

Outcome Measures

Primary Outcomes (2)

• 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.

  Day 1 post-op/standard of care first medication dose to day 90 (+/-14 days) post-op/standard of care

• 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.

  Day 1 post-op/standard of care first dose of medication to day 90 (+/- 14 days) post-op/standard of care

Secondary Outcomes (4)

• 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

• 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

• Number of Participants With a Patient Satisfaction Assessment

  On visit 4, which is 28 days (+/- 4 days) post-op/standard of care

• 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

Study Arms (2)

Oral apixaban

EXPERIMENTAL

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

Drug: Oral apixaban

Subcutaneous enoxaparin

ACTIVE COMPARATOR

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

Drug: Subcutaneous enoxaparin

Interventions

Oral apixaban 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.

Also known as: Eliquis

Oral apixaban

Subcutaneous enoxaparin 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.

Also known as: Lovenox

Subcutaneous enoxaparin

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

University of Southern California Keck School of Medicine

Los Angeles, California, 90089, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (2)

• 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.

  PMID: 32641236 DERIVED

• 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.

  PMID: 32589230 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism

Interventions

apixaban; Enoxaparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Dr. Saketh Guntupalli
• Organization: University of Colorado, Anschutz Medical Campus

saketh.guntupalli@cuanschutz.edu

303-724-2033

Study Officials

• Saketh Guntupalli, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2015
• First Posted: February 19, 2015
• Study Start: April 28, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: March 31, 2020
• Results First Posted: March 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)