Oral Apixaban (Eliquis) Versus Enoxaparin (Lovenox) for T... | NCT02366871

Status Module

Name	Class
Bristol-Myers Squibb	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

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

Eligibility Module

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

Name	Affiliation	Role
Saketh Guntupalli, MD	University of Colorado, Denver	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California Keck School of Medicine		Los Angeles	California	90089	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32641236	Derived	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.
32589230	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery Oral apixaban: To 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 QD for 28 days post surgery.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
ICF	No	No	Yes	Informed Consent Form	Jan 30, 2019	Jan 29, 2020

Arm/Group Information

ID	Title	Description
BG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.
BG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000204 BG001196 BG002400

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	BG00058.0(21.0 to 87.0) BG00158.5(18.0 to 89.0) BG00258.0(18.0 to 89.0)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000204 BG001196 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race/ethnic group

Title	Measurements
White Non-Hispanic	BG000158 BG001164 BG002

Surgical Intervention

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Open	BG000165 BG001152 BG002

Surgeries

Count of Participants

Participants

Title

Denominators

Categories

total abdominal hysterectomy(TAH) with BSO/USO

Title	Measurements
	BG000116 BG001112 BG002

Length of Surgery

Median

Inter-Quartile Range

minutes

Title

Denominators

Categories

Title	Measurements
	BG000204(31 to 600) BG001215.5(17 to 743) BG002

Confirm Origin

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Uterine Cancer	BG00065 BG00163 BG002

Stage

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Low stage (I/II)	BG00080 BG00185 BG002

Body-mass index

Median

Inter-Quartile Range

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00027.4(11.0 to 50.5) BG00126.5(15.8 to 57.2) BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.
OG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.

Units	Counts
Participants	OG000204 OG001196

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0011

Primary

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.
OG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.

Secondary

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.
OG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.

Secondary

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).

Posted

Count of Participants

Participants

Day 1 post-op/standard of care first dose of medication to Day 28 (+/- 4 days) post-op/standard of care

ID	Title	Description
OG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.
OG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.

Secondary

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.

One patient did not answer the "pain associated with taking the medication" category.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.
OG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.

Secondary

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.

Posted

Median

Inter-Quartile Range

score on a scale

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

ID	Title	Description
OG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.
OG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Oral Apixaban	Oral apixaban 2.5 mg tablet twice daily for 28 days post-surgery 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.	2	204	13	204	53	204
EG001	Subcutaneous Enoxaparin	Subcutaneous enoxaparin 40mg once daily (QD) for 28 days post-surgery. 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.	2	196	14	196	45	196

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Admitted for abdominal pain and emesis	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected204 at risk EG0011 affected196 at risk
Admitted for ileus	Surgical and medical procedures	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0010 affected196 at risk
Admitted for wound Infection	Surgical and medical procedures	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0013 affected196 at risk
Admitted for neutropenic fever from chemotherapy	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0011 affected196 at risk
Admitted for pneumonia	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected204 at risk EG0012 affected196 at risk
Admitted for excess kidney fluid and stent placement	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected204 at risk EG0011 affected196 at risk
Admitted for Nausea/emesis from chemotherapy	General disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected204 at risk EG0010 affected196 at risk
Admitted for dehydration	General disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected204 at risk EG0012 affected196 at risk
Admitted for clostridium difficile	Gastrointestinal disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected204 at risk EG0011 affected196 at risk
Admitted for small bowel obstruction	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0012 affected196 at risk
Admitted for pelvic infection	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0010 affected196 at risk
Admitted for wound closure	General disorders	CTCAE (4.0)	Systematic Assessment	EG0000 affected204 at risk EG0011 affected196 at risk
Admitted for vaginal cuff bleeding from open vessel from surgery stitches	Surgical and medical procedures	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0010 affected196 at risk
Admitted for nausea and stomach flu	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0010 affected196 at risk
Admitted for ongoing UTI/sepsis - resolved	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0010 affected196 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hematoma	Blood and lymphatic system disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0015 affected196 at risk
Wound infection	Surgical and medical procedures	CTCAE (4.0)	Systematic Assessment	EG0007 affected204 at risk EG00110 affected196 at risk
Dizziness	General disorders	CTCAE (4.0)	Systematic Assessment	EG00010 affected204 at risk EG0011 affected196 at risk
Suspected allergic reaction	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0011 affected196 at risk
Arthralgia	General disorders	CTCAE (4.0)	Systematic Assessment	EG0007 affected204 at risk EG0012 affected196 at risk
Bruising	General disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected204 at risk EG00111 affected196 at risk
Skin rash/cellulitis	General disorders	CTCAE (4.0)	Systematic Assessment	EG0001 affected204 at risk EG0012 affected196 at risk
Vaginal spotting/discharge/bleeding	General disorders	CTCAE (4.0)	Systematic Assessment	EG0004 affected204 at risk EG0011 affected196 at risk
Epistaxis	General disorders	CTCAE (4.0)	Systematic Assessment	EG0003 affected204 at risk EG0012 affected196 at risk
Abscess/discharge from incision	General disorders	CTCAE (4.0)	Systematic Assessment	EG0002 affected204 at risk EG0010 affected196 at risk
Headache	General disorders	CTCAE (4.0)	Systematic Assessment	EG0007 affected204 at risk EG0015 affected196 at risk
Hospitalized in 28 days	General disorders	CTCAE (4.0)	Systematic Assessment	EG0006 affected204 at risk EG0015 affected196 at risk

ID	Term
D013923	Thromboembolism
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Term
D006495	Heparin, Low-Molecular-Weight
D006493	Heparin
D006025	Glycosaminoglycans
D011134	Polysaccharides
D002241	Carbohydrates