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

Primary Purpose

Gynecologic Cancer, Venous Thromboembolism

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Oral apixaban
Subcutaneous enoxaparin
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Gynecologic Cancer

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of Southern California Keck School of Medicine
  • University of Colorado Denver

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Oral apixaban

Subcutaneous enoxaparin

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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).
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.
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.

Full Information

First Posted
February 2, 2015
Last Updated
March 17, 2020
Sponsor
University of Colorado, Denver
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02366871
Brief Title
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

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
April 28, 2015 (Actual)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gynecologic Cancer, Venous Thromboembolism

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
400 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral apixaban
Arm Type
Experimental
Arm Description
Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery
Arm Title
Subcutaneous enoxaparin
Arm Type
Active Comparator
Arm Description
Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery.
Intervention Type
Drug
Intervention Name(s)
Oral apixaban
Other Intervention Name(s)
Eliquis
Intervention Description
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
Intervention Name(s)
Subcutaneous enoxaparin
Other Intervention Name(s)
Lovenox
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Incidence of Major Bleeding
Description
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
Title
Number of Participants With Incidence of Clinically Relevant Non Major Bleeding Events
Description
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
Secondary Outcome Measure Information:
Title
Number of Participants With Incidence of Venous Thromboembolism (VTEs): Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
Description
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
Title
Number of Participants Who Met Medication Adherence Rates
Description
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
Title
Number of Participants With a Patient Satisfaction Assessment
Description
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
Title
Change in Quality of Life From Baseline to 28 Days Post-op
Description
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saketh Guntupalli, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California Keck School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Facility Name
University of Colorado Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32641236
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.
Results Reference
derived
PubMed Identifier
32589230
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.
Results Reference
derived

Learn more about this trial

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

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