Apixaban or Dalteparin in Reducing Blood Clots in Patients With Cancer Related Venous Thromboembolism

• Sponsor: Academic and Community Cancer Research United (Other)
• Overall Status: Completed
• CT.gov ID: NCT02585713
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 300
• Locations: 18
• Arms: 2
• Actual Duration (Months): 49.1
• Patients Per Site: 16.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This randomized phase III trial studies the side effects of and compares apixaban and dalteparin in reducing blood clots in patients with cancer-related venous thromboembolism. Venous thromboembolism is a condition in which a blood clot forms in a vein and then breaks off and moves through the bloodstream. Patients with cancer are at increased risk for venous thromboembolism. Apixaban and dalteparin are drugs used to prevent blood clots from forming or to treat blood clots that have formed. It is not yet known whether apixaban or dalteparin is more effective in reducing blood clots in patients with cancer related venous thromboembolism.

ADAM-VTE

Condition or Disease	Intervention/Treatment	Phase
Cerebral Vein Thrombosis; Deep Vein Thrombosis; Gonadal Thrombosis; Hepatic Thrombosis; Malignant Neoplasm; Mesenteric Thrombosis; Metastatic Malignant Neoplasm; Portal Vein Thrombosis; Pulmonary Embolism; Renal Vein Thrombosis; Splenic Thrombosis; Venous Thromboembolism	Drug: Apixaban; Drug: Dalteparin; Other: Questionnaire Administration	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. Any episode of major bleeding including fatal bleeding.

SECONDARY OBJECTIVES:

1. Venous thromboembolism (VTE) recurrence including deep vein thrombosis (DVT), pulmonary embolism (PE), fatal PE, or arterial thromboembolism.

2. Any episode of major bleeding including fatal bleeding or any episode of clinically relevant non-major bleeding.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive apixaban 10 mg orally (PO) twice daily (BID) on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.

ARM II: Patients receive dalteparin 200 international units (IU)/kg/day subcutaneously (SC) once daily (QD) on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.

After completion of study treatment, patients are followed up at 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Phase III, Randomized, Open Label Study Evaluating the Safety of Apixaban in Subjects With Cancer Related Venous Thromboembolism
• Actual Study Start Date: Nov 20, 2015
• Actual Primary Completion Date: Apr 2, 2018
• Actual Study Completion Date: Dec 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (apixaban) Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.	Drug: Apixaban; Given PO; Other Names: BMS-562247 BMS-562247-01 Eliquis ; Other: Questionnaire Administration; Ancillary studies
Experimental: Arm II (dalteparin) Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.	Drug: Dalteparin; Given SC; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. 6 Month Bleeding Rate [Up to 6 months]

   The rate (percentage) of patients experiencing major bleeding at 6 months from treatment initiation and its associated 95% confidence interval was estimated separately by treatment arm using a cumulative incidence function, treating death without bleeding as a competing risk.

Secondary Outcome Measures

1. Composite Bleeding Rate: Major Bleed or a Clinically Relevant Non-major Bleed [Up to 6 months]

   A similar analysis as described for the primary safety analysis will be used. The rate (percentage) of patients experiencing major bleeding or a clinically relevant non-major bleed at 6 months from treatment initiation and its associated 95% confidence interval was estimated separately by treatment arm using a cumulative incidence function, treating death without bleeding as a competing risk.

2. Time to the First Event of the Composite Deep Vein Thrombosis (DVT)/Pulmonary Embolism (PE) [Up to 3 months post-treatment]

   Analyzed using the same methods described above for the primary endpoint.Time to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) is defined as the time from randomization to the date the patient experienced the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed acute lower extremity or upper extremity (jugular, innominate, subclavian, axillary, brachial) DVT, PE, splanchnic (hepatic, portal, splenic, mesenteric, renal, gonadal), or cerebral vein thrombosis

• Active cancer defined as metastatic disease and/or any evidence of cancer on cross-sectional or positron emission tomography (PET) imaging, cancer related surgery, chemotherapy or radiation therapy within the past 6 months; note: non-melanoma skin cancer does not meet the cancer requirement

• Life expectancy >= 60 days

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

• Obtained =< 30 days prior to randomization: Platelet count >= 50,000/mm^3

• Obtained =< 30 days prior to randomization: Alanine aminotransferase (ALT) or aspartate transaminase (AST) =< 3 x upper limit of normal (ULN)

• Obtained =< 30 days prior to randomization: International normalized ratio (INR) =< 1.6 (if not taking anticoagulant therapy)

• Obtained =< 30 days prior to randomization: Calculated creatinine clearance must be >= 30 ml/min using the Cockcroft-Gault formula

• Negative serum or urine pregnancy test done =< 24 hours prior to randomization, for women of childbearing potential only; note: a women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal; menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes

• Ability to complete questionnaire(s) by themselves or with assistance

• Ability to provide informed written consent

• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• Note: women of child bearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 33 days after finishing the last dose

• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 93 days after finishing the last dose

• Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however they must still undergo pregnancy testing as described in this section

• Note: investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception; highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly

• At a minimum, subjects must agree to the use of one method of highly effective contraception as listed below:

• HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

• Male condoms with spermicide

• Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subject?s WOCBP partner

• Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug

• IUDs, such as ParaGard

• Tubal ligation

• Vasectomy

• Complete abstinence

• Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs; female subjects must continue to have pregnancy tests; acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence

• Treatment with an anticoagulant for more than 7 days for the current blood clot, prior to randomization

• Active bleeding

• Severe hypersensitivity reaction to apixaban, dalteparin, heparin or pork products (e.g., anaphylactic reactions)

• Use of the following CYP3A4 inducers: rifampin, rifabutin, carbamazepine, efavirenz, phenobarbital, phenytoin, fosphenytoin, primidone, and St. John?s wort)

• Thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) that will be continued on study

• Severe liver disease (known cirrhosis Childs Pugh class B or C), or active hepatitis

• Use of a Factor Xa inhibitor (e.g. apixaban, rivaroxaban, or edoxaban) =< 3 months prior to randomization

• Treatment of a thromboembolic event =< 6 months prior to randomization

• Documented venous thromboembolism while on therapeutic anticoagulation (?anticoagulation failure?)

• Mechanical heart valve

• Documented hemorrhagic tendencies

• Bacterial endocarditis

• History of heparin induced thrombocytopenia

• Any of the following conditions:

• Intracranial bleeding =< 6 months prior to randomization

• Intraocular bleeding =< 6 months prior to randomization

• Gastrointestinal bleeding and/or endoscopically proven ulcer =< 6 months prior to randomization

• Head trauma or major trauma =<1 month prior to randomization

• Neurosurgery =< 2 weeks prior to randomization

• Major surgery =< 1 week prior to randomization

• Overt major bleeding at the time of randomization

• Gross hematuria at the time of randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
3	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
4	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
5	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
6	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
7	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
8	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
11	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
12	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
13	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire	United States	03106
14	FirstHealth of the Carolinas-Moore Regional Hosiptal	Pinehurst	North Carolina	United States	28374
15	Columbus NCI Community Oncology Research Program	Columbus	Ohio	United States	43215
16	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
17	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
18	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701

Sponsors and Collaborators

• Academic and Community Cancer Research United
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Robert McBane, Academic and Community Cancer Research United

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 1, 2017

More Information

Publications

None provided.

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT02585713
• Other Study ID Numbers: RU221501I; NCI-2015-01573; CV185-444; RU221501I
• First Posted: Oct 23, 2015
• Last Update Posted: Aug 4, 2020
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Neoplasms; Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Venous Thrombosis; Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight; Apixaban

Study Results

Participant Flow

Arm/Group Title	Arm A (Apixaban)	Arm B (Dalteparin)
Arm/Group Description	Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.	Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.
Period Title: Overall Study
STARTED	150	150
COMPLETED	145	142
NOT COMPLETED	5	8

Baseline Characteristics

Arm/Group Title	Arm A (Apixaban)	Arm B (Dalteparin)	Total
Arm/Group Description	Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.	Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.	Total of all reporting groups
Overall Participants	150	150	300
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.4 (11.3)	64.0 (10.8)	64.2 (11.0)
Sex: Female, Male (Count of Participants)
Female	78 52%	77 51.3%	155 51.7%
Male	72 48%	73 48.7%	145 48.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	1 0.3%
Asian	2 1.3%	0 0%	2 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 4%	11 7.3%	17 5.7%
White	140 93.3%	138 92%	278 92.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.7%	1 0.7%	2 0.7%
ECOG Performance Status (Count of Participants)
0	60 40%	62 41.3%	122 40.7%
1	70 46.7%	76 50.7%	146 48.7%
2	20 13.3%	12 8%	32 10.7%

Outcome Measures

1. Primary Outcome

Title	6 Month Bleeding Rate
Description	The rate (percentage) of patients experiencing major bleeding at 6 months from treatment initiation and its associated 95% confidence interval was estimated separately by treatment arm using a cumulative incidence function, treating death without bleeding as a competing risk.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Primary Analysis Population

Arm/Group Title	Arm A (Apixaban)	Arm B (Dalteparin)
Arm/Group Description	Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.	Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.
Measure Participants	145	142
Number (95% Confidence Interval) [percentage of patients]	0	2.1

2. Secondary Outcome

Title	Composite Bleeding Rate: Major Bleed or a Clinically Relevant Non-major Bleed
Description	A similar analysis as described for the primary safety analysis will be used. The rate (percentage) of patients experiencing major bleeding or a clinically relevant non-major bleed at 6 months from treatment initiation and its associated 95% confidence interval was estimated separately by treatment arm using a cumulative incidence function, treating death without bleeding as a competing risk.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Apixaban)	Arm B (Dalteparin)
Arm/Group Description	Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.	Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.
Measure Participants	145	142
Number (95% Confidence Interval) [percentage of patients]	7.0	8.1

3. Secondary Outcome

Title	Time to the First Event of the Composite Deep Vein Thrombosis (DVT)/Pulmonary Embolism (PE)
Description	Analyzed using the same methods described above for the primary endpoint.Time to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) is defined as the time from randomization to the date the patient experienced the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE).
Time Frame	Up to 3 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Apixaban)	Arm B (Dalteparin)
Arm/Group Description	Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.	Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.
Measure Participants	149	149
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Apixaban), Arm B (Dalteparin)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1316
	Comments
	Method	Log Rank
	Comments

Adverse Events

Time Frame	Up to 3 months after completion of treatment
Adverse Event Reporting Description	Adverse events are summarized below for patients who received at least one cycle of treatment (i.e. patients who completed the study and patients with unknown reason for not completing the study in the Participant Flow) and completed at least one adverse event form.
Arm/Group Title	Arm A (Apixaban)		Arm B (Dalteparin)
Arm/Group Description	Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.		Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.
All Cause Mortality
	Arm A (Apixaban)		Arm B (Dalteparin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/148 (23.6%)		25/143 (17.5%)
Serious Adverse Events
	Arm A (Apixaban)		Arm B (Dalteparin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/148 (41.9%)		51/143 (35.7%)
Blood and lymphatic system disorders
Anemia	3/148 (2%)	3	3/143 (2.1%)	3
Febrile neutropenia	1/148 (0.7%)	2	2/143 (1.4%)	2
Cardiac disorders
Acute coronary syndrome	1/148 (0.7%)	1	0/143 (0%)	0
Atrial flutter	0/148 (0%)	0	1/143 (0.7%)	2
Heart failure	1/148 (0.7%)	1	1/143 (0.7%)	1
Left ventricular systolic dysfunction	1/148 (0.7%)	1	0/143 (0%)	0
Pericardial effusion	0/148 (0%)	0	2/143 (1.4%)	2
Pericardial tamponade	0/148 (0%)	0	1/143 (0.7%)	1
Gastrointestinal disorders
Abdominal pain	0/148 (0%)	0	4/143 (2.8%)	4
Ascites	0/148 (0%)	0	1/143 (0.7%)	1
Colitis	1/148 (0.7%)	2	0/143 (0%)	0
Colonic perforation	2/148 (1.4%)	2	0/143 (0%)	0
Constipation	0/148 (0%)	0	1/143 (0.7%)	1
Diarrhea	2/148 (1.4%)	2	3/143 (2.1%)	3
Duodenal obstruction	1/148 (0.7%)	2	0/143 (0%)	0
Dysphagia	1/148 (0.7%)	1	0/143 (0%)	0
Enterocolitis	2/148 (1.4%)	3	0/143 (0%)	0
Esophageal obstruction	1/148 (0.7%)	1	1/143 (0.7%)	2
Gastric hemorrhage	0/148 (0%)	0	1/143 (0.7%)	1
Lower gastrointestinal hemorrhage	1/148 (0.7%)	1	0/143 (0%)	0
Mucositis oral	1/148 (0.7%)	1	1/143 (0.7%)	1
Nausea	2/148 (1.4%)	3	3/143 (2.1%)	3
Pancreatic necrosis	0/148 (0%)	0	1/143 (0.7%)	1
Retroperitoneal hemorrhage	0/148 (0%)	0	1/143 (0.7%)	1
Small intestinal obstruction	2/148 (1.4%)	2	2/143 (1.4%)	2
Upper gastrointestinal hemorrhage	1/148 (0.7%)	1	0/143 (0%)	0
Vomiting	2/148 (1.4%)	3	3/143 (2.1%)	3
General disorders
Death NOS	3/148 (2%)	3	1/143 (0.7%)	1
Edema face	0/148 (0%)	0	1/143 (0.7%)	1
Edema limbs	0/148 (0%)	0	2/143 (1.4%)	3
Fatigue	1/148 (0.7%)	1	1/143 (0.7%)	1
Fever	0/148 (0%)	0	1/143 (0.7%)	1
Gait disturbance	0/148 (0%)	0	1/143 (0.7%)	1
General disorders and administration site conditions - Other, specify	1/148 (0.7%)	1	0/143 (0%)	0
Non-cardiac chest pain	0/148 (0%)	0	1/143 (0.7%)	1
Hepatobiliary disorders
Cholecystitis	0/148 (0%)	0	1/143 (0.7%)	1
Hepatobiliary disorders - Other, specify	0/148 (0%)	0	1/143 (0.7%)	2
Immune system disorders
Immune system disorders - Other, specify	0/148 (0%)	0	1/143 (0.7%)	1
Infections and infestations
Abdominal infection	0/148 (0%)	0	1/143 (0.7%)	1
Appendicitis	1/148 (0.7%)	1	0/143 (0%)	0
Esophageal infection	1/148 (0.7%)	1	0/143 (0%)	0
Hepatic infection	0/148 (0%)	0	1/143 (0.7%)	1
Infections and infestations - Other, specify	0/148 (0%)	0	3/143 (2.1%)	4
Lung infection	5/148 (3.4%)	5	3/143 (2.1%)	4
Sepsis	1/148 (0.7%)	1	5/143 (3.5%)	6
Skin infection	0/148 (0%)	0	1/143 (0.7%)	1
Urinary tract infection	4/148 (2.7%)	4	1/143 (0.7%)	1
Injury, poisoning and procedural complications
Fall	3/148 (2%)	3	0/143 (0%)	0
Fracture	3/148 (2%)	3	1/143 (0.7%)	2
Investigations
Alanine aminotransferase increased	0/148 (0%)	0	1/143 (0.7%)	2
Aspartate aminotransferase increased	0/148 (0%)	0	1/143 (0.7%)	2
Cardiac troponin I increased	1/148 (0.7%)	1	0/143 (0%)	0
Creatinine increased	1/148 (0.7%)	1	3/143 (2.1%)	3
INR increased	0/148 (0%)	0	1/143 (0.7%)	1
Lymphocyte count decreased	2/148 (1.4%)	2	1/143 (0.7%)	3
Neutrophil count decreased	1/148 (0.7%)	1	0/143 (0%)	0
Platelet count decreased	3/148 (2%)	3	1/143 (0.7%)	1
Weight gain	0/148 (0%)	0	1/143 (0.7%)	1
White blood cell decreased	1/148 (0.7%)	1	1/143 (0.7%)	1
Metabolism and nutrition disorders
Anorexia	0/148 (0%)	0	1/143 (0.7%)	1
Dehydration	1/148 (0.7%)	1	2/143 (1.4%)	2
Hyperglycemia	0/148 (0%)	0	1/143 (0.7%)	2
Hyperkalemia	1/148 (0.7%)	1	0/143 (0%)	0
Hyperuricemia	0/148 (0%)	0	1/143 (0.7%)	1
Hypoalbuminemia	0/148 (0%)	0	1/143 (0.7%)	1
Hypocalcemia	0/148 (0%)	0	1/143 (0.7%)	1
Hypokalemia	0/148 (0%)	0	2/143 (1.4%)	2
Hyponatremia	1/148 (0.7%)	1	2/143 (1.4%)	4
Hypophosphatemia	0/148 (0%)	0	1/143 (0.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/148 (1.4%)	2	1/143 (0.7%)	1
Flank pain	1/148 (0.7%)	1	1/143 (0.7%)	1
Generalized muscle weakness	1/148 (0.7%)	1	1/143 (0.7%)	1
Osteonecrosis of jaw	1/148 (0.7%)	1	0/143 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	32/148 (21.6%)	35	24/143 (16.8%)	26
Tumor pain	1/148 (0.7%)	1	1/143 (0.7%)	1
Nervous system disorders
Cognitive disturbance	0/148 (0%)	0	1/143 (0.7%)	1
Dysarthria	1/148 (0.7%)	1	0/143 (0%)	0
Headache	3/148 (2%)	3	0/143 (0%)	0
Somnolence	1/148 (0.7%)	1	0/143 (0%)	0
Stroke	1/148 (0.7%)	1	1/143 (0.7%)	1
Syncope	1/148 (0.7%)	1	1/143 (0.7%)	1
Psychiatric disorders
Anxiety	1/148 (0.7%)	1	0/143 (0%)	0
Depression	1/148 (0.7%)	1	0/143 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/148 (0%)	0	2/143 (1.4%)	2
Chronic kidney disease	1/148 (0.7%)	1	2/143 (1.4%)	2
Reproductive system and breast disorders
Fallopian tube obstruction	0/148 (0%)	0	1/143 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/148 (0.7%)	1	0/143 (0%)	0
Bronchopulmonary hemorrhage	1/148 (0.7%)	1	0/143 (0%)	0
Cough	0/148 (0%)	0	1/143 (0.7%)	1
Dyspnea	0/148 (0%)	0	1/143 (0.7%)	1
Hypoxia	2/148 (1.4%)	2	0/143 (0%)	0
Pleural effusion	1/148 (0.7%)	1	1/143 (0.7%)	2
Pneumonitis	2/148 (1.4%)	2	0/143 (0%)	0
Respiratory failure	2/148 (1.4%)	2	1/143 (0.7%)	1
Surgical and medical procedures
Surgical and medical procedures - Other, specify	0/148 (0%)	0	1/143 (0.7%)	1
Vascular disorders
Bleeding	2/148 (1.4%)	2	7/143 (4.9%)	7
Hematoma	0/148 (0%)	0	1/143 (0.7%)	1
Hypertension	2/148 (1.4%)	3	0/143 (0%)	0
Hypotension	1/148 (0.7%)	1	1/143 (0.7%)	1
Thromboembolic event	1/148 (0.7%)	2	4/143 (2.8%)	4
Other (Not Including Serious) Adverse Events
	Arm A (Apixaban)		Arm B (Dalteparin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/148 (52.7%)		71/143 (49.7%)
Blood and lymphatic system disorders
Anemia	14/148 (9.5%)	28	12/143 (8.4%)	22
Febrile neutropenia	0/148 (0%)	0	2/143 (1.4%)	2
Cardiac disorders
Cardiac disorders - Other, specify	0/148 (0%)	0	1/143 (0.7%)	1
Chest pain - cardiac	1/148 (0.7%)	1	0/143 (0%)	0
Conduction disorder	0/148 (0%)	0	1/143 (0.7%)	1
Pericardial effusion	0/148 (0%)	0	1/143 (0.7%)	1
Ventricular tachycardia	1/148 (0.7%)	4	0/143 (0%)	0
Endocrine disorders
Hypothyroidism	2/148 (1.4%)	2	1/143 (0.7%)	1
Eye disorders
Conjunctivitis	0/148 (0%)	0	1/143 (0.7%)	1
Retinal vascular disorder	0/148 (0%)	0	1/143 (0.7%)	2
Gastrointestinal disorders
Abdominal distension	0/148 (0%)	0	1/143 (0.7%)	1
Abdominal pain	2/148 (1.4%)	2	0/143 (0%)	0
Ascites	0/148 (0%)	0	1/143 (0.7%)	1
Colonic obstruction	1/148 (0.7%)	1	0/143 (0%)	0
Constipation	1/148 (0.7%)	1	0/143 (0%)	0
Diarrhea	4/148 (2.7%)	6	3/143 (2.1%)	3
Enterocolitis	1/148 (0.7%)	1	0/143 (0%)	0
Gastroesophageal reflux disease	1/148 (0.7%)	1	0/143 (0%)	0
Mucositis oral	0/148 (0%)	0	2/143 (1.4%)	2
Nausea	4/148 (2.7%)	4	3/143 (2.1%)	3
Vomiting	1/148 (0.7%)	1	3/143 (2.1%)	3
General disorders
Edema limbs	1/148 (0.7%)	1	1/143 (0.7%)	1
Fatigue	2/148 (1.4%)	2	1/143 (0.7%)	1
Injection site reaction	0/148 (0%)	0	29/143 (20.3%)	70
Pain	2/148 (1.4%)	2	1/143 (0.7%)	1
Infections and infestations
Abdominal infection	1/148 (0.7%)	1	0/143 (0%)	0
Bone infection	1/148 (0.7%)	1	0/143 (0%)	0
Bronchial infection	1/148 (0.7%)	2	0/143 (0%)	0
Conjunctivitis infective	0/148 (0%)	0	1/143 (0.7%)	1
Enterocolitis infectious	0/148 (0%)	0	1/143 (0.7%)	1
Infections and infestations - Other, specify	0/148 (0%)	0	1/143 (0.7%)	1
Lung infection	2/148 (1.4%)	2	0/143 (0%)	0
Mucosal infection	0/148 (0%)	0	2/143 (1.4%)	2
Papulopustular rash	0/148 (0%)	0	1/143 (0.7%)	1
Sepsis	2/148 (1.4%)	2	0/143 (0%)	0
Urinary tract infection	2/148 (1.4%)	2	2/143 (1.4%)	2
Injury, poisoning and procedural complications
Bruising	0/148 (0%)	0	2/143 (1.4%)	2
Spinal fracture	0/148 (0%)	0	1/143 (0.7%)	1
Investigations
Alanine aminotransferase increased	1/148 (0.7%)	1	2/143 (1.4%)	2
Alkaline phosphatase increased	3/148 (2%)	4	2/143 (1.4%)	2
Aspartate aminotransferase increased	3/148 (2%)	3	1/143 (0.7%)	1
Blood bilirubin increased	2/148 (1.4%)	2	2/143 (1.4%)	3
Cardiac troponin I increased	1/148 (0.7%)	1	0/143 (0%)	0
Creatinine increased	1/148 (0.7%)	1	2/143 (1.4%)	2
INR increased	1/148 (0.7%)	1	1/143 (0.7%)	1
Lymphocyte count decreased	9/148 (6.1%)	18	8/143 (5.6%)	13
Lymphocyte count increased	1/148 (0.7%)	1	1/143 (0.7%)	1
Neutrophil count decreased	10/148 (6.8%)	16	7/143 (4.9%)	23
Platelet count decreased	40/148 (27%)	93	26/143 (18.2%)	71
Weight gain	1/148 (0.7%)	1	0/143 (0%)	0
Weight loss	2/148 (1.4%)	3	1/143 (0.7%)	1
White blood cell decreased	7/148 (4.7%)	16	7/143 (4.9%)	21
Metabolism and nutrition disorders
Anorexia	3/148 (2%)	3	1/143 (0.7%)	1
Dehydration	1/148 (0.7%)	1	0/143 (0%)	0
Hypercalcemia	1/148 (0.7%)	1	0/143 (0%)	0
Hyperglycemia	1/148 (0.7%)	2	1/143 (0.7%)	1
Hyperkalemia	0/148 (0%)	0	1/143 (0.7%)	1
Hypoalbuminemia	3/148 (2%)	3	3/143 (2.1%)	3
Hypocalcemia	1/148 (0.7%)	1	2/143 (1.4%)	3
Hypokalemia	2/148 (1.4%)	4	4/143 (2.8%)	7
Hypomagnesemia	1/148 (0.7%)	1	0/143 (0%)	0
Hyponatremia	0/148 (0%)	0	3/143 (2.1%)	3
Hypophosphatemia	1/148 (0.7%)	1	1/143 (0.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/148 (0.7%)	2	0/143 (0%)	0
Back pain	1/148 (0.7%)	1	1/143 (0.7%)	2
Generalized muscle weakness	2/148 (1.4%)	3	2/143 (1.4%)	3
Muscle weakness lower limb	1/148 (0.7%)	1	0/143 (0%)	0
Myalgia	1/148 (0.7%)	1	1/143 (0.7%)	1
Pain in extremity	0/148 (0%)	0	1/143 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0/148 (0%)	0	1/143 (0.7%)	1
Nervous system disorders
Depressed level of consciousness	1/148 (0.7%)	1	0/143 (0%)	0
Encephalopathy	1/148 (0.7%)	1	0/143 (0%)	0
Headache	3/148 (2%)	3	0/143 (0%)	0
Peripheral sensory neuropathy	1/148 (0.7%)	1	1/143 (0.7%)	1
Somnolence	1/148 (0.7%)	1	0/143 (0%)	0
Syncope	1/148 (0.7%)	1	0/143 (0%)	0
Psychiatric disorders
Anxiety	0/148 (0%)	0	1/143 (0.7%)	1
Confusion	0/148 (0%)	0	1/143 (0.7%)	1
Insomnia	0/148 (0%)	0	1/143 (0.7%)	1
Renal and urinary disorders
Chronic kidney disease	2/148 (1.4%)	5	0/143 (0%)	0
Urinary retention	0/148 (0%)	0	2/143 (1.4%)	2
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify	0/148 (0%)	0	1/143 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/148 (0.7%)	1	0/143 (0%)	0
Allergic rhinitis	0/148 (0%)	0	1/143 (0.7%)	1
Cough	1/148 (0.7%)	1	1/143 (0.7%)	1
Dyspnea	3/148 (2%)	3	1/143 (0.7%)	1
Hypoxia	1/148 (0.7%)	1	2/143 (1.4%)	2
Pleural effusion	1/148 (0.7%)	1	1/143 (0.7%)	1
Pneumothorax	1/148 (0.7%)	1	1/143 (0.7%)	1
Wheezing	1/148 (0.7%)	1	0/143 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/148 (0.7%)	1	1/143 (0.7%)	1
Skin and subcutaneous tissue disorders - Other, specify	0/148 (0%)	0	1/143 (0.7%)	1
Vascular disorders
Bleeding	31/148 (20.9%)	38	23/143 (16.1%)	27
Hypertension	5/148 (3.4%)	9	2/143 (1.4%)	3
Hypotension	0/148 (0%)	0	2/143 (1.4%)	2
Thromboembolic event	0/148 (0%)	0	2/143 (1.4%)	2
Vascular disorders - Other, specify	2/148 (1.4%)	3	0/143 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.