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

Mayo Clinic

Status and phase

Completed

Phase 3

Conditions

Venous Thromboembolism

Malignant Neoplasm

Renal Vein Thrombosis

Splenic Thrombosis

Portal Vein Thrombosis

Metastatic Malignant Neoplasm

Mesenteric Thrombosis

Pulmonary Embolism

Hepatic Thrombosis

Deep Vein Thrombosis

Cerebral Vein Thrombosis

Gonadal Thrombosis

Treatments

Drug: Apixaban

Other: Questionnaire Administration

Drug: Dalteparin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02585713

CV185-444

NCI-2015-01573 (Registry Identifier)

RU221501I (Other Identifier)

Details and patient eligibility

About

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

Full description

PRIMARY OBJECTIVES:

I. Any episode of major bleeding including fatal bleeding.

SECONDARY OBJECTIVES:

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

II. 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.

Enrollment

300 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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