Clinical trial NCT03590743: Calf Deep Vein Thrombosis Treatment Trial
Official title: A Phase IV, Randomized, Double Blind Study Evaluating the Safety and Efficacy of Apixaban in Subjects With Calf Vein Thrombosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Deep Vein Thrombosis
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Pfizer
First posted: 2018-07-18
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Multicenter, randomized, double blind, placebo-controlled, superiority clinical trial.
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a randomized double-blind placebo controlled superiority clinical trial. Patients will be identified at the time of the diagnosis of acute calf deep vein thrombosis and approached at that time. If they agree they would be randomly assigned to placebo or apixaban treatment for three months. Along with this they will also undergo repeat ultrasounds at 7, 14, and 90 days along with telephone follow-up at 30 and 60 days.

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.

Primary outcomes:
measure: Number of Subjects Who Experience a Composite Venous Thromboembolism (VTE) Event Within 3 Months
timeFrame: Within 3 months of therapy initiation
measure: Number of Subjects Who Experience Either Major Bleeding or Clinically Relevant Non-major Bleeding Within 3 Months
timeFrame: Within 3 months of therapy initiation
Secondary outcomes:
measure: Mean Time of Thrombus Propagation
timeFrame: Within 3 months of therapy initiation
measure: Net Clinical Benefit or Harm for the Two Strategies
timeFrame: Within 3 months of therapy initiation.
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Eau Claire
country: United States
facility: Mayo Clinic
state: Wisconsin
city: La Crosse
country: United States
facility: Mayo Clinic
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Robert D McBane
role: PRINCIPAL_INVESTIGATOR
References: