Calf Deep Vein Thrombosis Treatment Trial
Condition: Deep Vein Thrombosis
MeSH terms: Thrombosis; Venous Thrombosis
Intervention: Apixaban; Placebo
Intervention description: Active anticoagulation with apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily to complete a total of 3 months treatment.; apixaban matching placebo 2 tablets twice daily for 7 days followed by one tablet twice daily to complete a total of 3 months.
Intervention MeSH terms: Apixaban
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: Multicenter, randomized, double blind, placebo-controlled, superiority clinical trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double blind, placebo controlled
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective is to evaluate whether apixaban is more effective in treating patients
      with isolated calf vein thrombosis (DVT) than serial imaging of the DVT for preventing
      thrombus spread, pulmonary embolism (PE) and/or recurring DVTs.
    

Eligibility criteria:

        Inclusion Criteria

          1. Age range: ≥ 18 years.

          2. Both males and females

          3. Confirmed acute calf vein thrombosis confined to either the deep (posterior tibial,
             anterior tibial, or peroneal) or muscular (gastrocnemius or soleal) veins.

          4. Negative serum or urine pregnancy test done (within 2 weeks) prior to randomization,
             for women of childbearing potential only. Note: A woman 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.

          5. Ability to provide written informed consent.

        Exclusion criteria

          1. Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  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. Acceptable alternate methods of highly effective contraception must be
                  discussed in the event that the subject chooses to forego complete abstinence

          2. Acute co-existing proximal DVT (popliteal, femoral, iliac veins or IVC), pulmonary
             embolism, splanchnic vein thrombosis, cerebral venous sinus thrombosis within the past
             3 months for whom anticoagulation therapy is indicated.

          3. Age < 18 years.

          4. Continuous treatment with therapeutic anticoagulant for more than 72 hours
             pre-randomization.

          5. Contraindication to anticoagulant therapy

          6. Significant kidney disease. Creatinine clearance < 25 ml/min using the Cockcroft-Gault
             equation: glomerular filtration rate (GFR) = (140-age) * (Wt in kg) * (0.85 if female)
             / (72 * Cr). (within last four weeks)

          7. Significant liver disease (e.g. acute hepatitis, chronic active hepatitis, cirrhosis)
             or alanine transaminase (ALT) (or AST) > 3 x upper limit of normal (ULN). (within last
             four weeks)

          8. Platelet count < 50 x109/L.(within last four weeks)

          9. Life expectancy < 12 months.

         10. Current active bleeding.

         11. Concomitant use of strong CYP3A4 inhibitors (e.g., HIV protease inhibitors, systemic
             ketoconazole) or strong CYP3A4 inducers like rifampicin.

         12. Active cancer defined as any evidence of cancer on cross-sectional imaging or cancer
             treatments within the past 6 months (chemotherapy, radiation therapy or cancer related
             surgery).

         13. . Anticipated need for urgent/emergent surgery or major invasive procedure.

         14. Dual antiplatelet therapy (thienopyridine plus aspirin) and/or aspirin greater than
             165 mg while on study medication.