Prophylactic Enoxaparin Dosing for Prevention of Venous Thromboembolism in Pregnancy.
Condition: Venous Thrombosis
MeSH terms: Thrombosis; Thromboembolism; Venous Thromboembolism; Venous Thrombosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Enoxaparin is a type of low molecular weight heparin (LMWH), or anticoagulant, used to
      prevent and treat blood clots. Formation of blood clots, or venous thromboemboli (VTE) in
      pregnancy can have dangerous and even life-threatening effects on the mother and fetus.
      Enoxaparin is the preferred medicine to prevent clotting in pregnant patients who are at risk
      for VTE, because it has been studied to be safe and effective in pregnancy without any harms
      to the fetus. Although this medication is routinely used and is recommended by several
      prominent medical groups, the optimal dosing for prevention of VTE is still unclear. The
      range of standardly prescribed dosing regimens of Enoxaparin includes 40mg daily and 1mg/kg
      daily, but these two dosing strategies have never been compared in a head to head fashion.
    

Detailed description: 
      When pregnant patients are diagnosed by their physician as being at risk for VTE, or when
      they enter the perinatology practice on a previously-prescribed prophylactic enoxaparin
      regimen, they will be offered a chance to discuss participation in the study. The patient
      will be consented and those who are not already receiving enoxaparin will be prescribed one
      of the two dosing regimens, at their physician's discretion, at that same clinic visit.

      A baseline blood sample will be drawn to assess coagulation using thromboelastography [TEG].
      TEG is a point-of-care device which measures the viscoelastic properties of clot formation.
      This device can provide rapid and detailed information about coagulation changes. TEG will be
      used to assess coagulation changes after commencing treatment with enoxaparin (see later).

      As per routine care, the patient will be instructed by the clinic nurse on how to fill her
      prescription at the pharmacy, how to give herself the injection subcutaneously once daily in
      the morning, and how to troubleshoot the injection process. As per routine care, the patient
      will have the opportunity to ask all questions necessary about this process, and her
      understanding and ability to comply with the injection procedures will be assessed by the
      clinic RN. The patient will be given a new prescription as needed by her physician at her
      regularly scheduled MD appointment. At any time, as per routine care, the patient can have
      the opportunity to review or troubleshoot the injection process with the RN or MD in the
      clinic. At each clinic visit, as per routine care, approximately 1-2 times per month as per
      routine care, the patient will be weighed and her weight recorded in her prenatal chart. At
      each of these visits the patient will also be asked a series of questions as per the study
      flowsheet in the chart, about potential side effects or adverse events she may have
      experienced since her last visit. In addition, she will receive a phone call from one of the
      study investigators once to twice per month to enquire about side effects, medication
      tolerability, and medication compliance. At 3 predetermined intervals throughout the
      pregnancy, the patient will be instructed to give a blood sample at the outpatient
      laboratory. When at all possible, these blood draws will be coordinated to coincide with the
      patient's regularly scheduled prenatal care blood draws, to minimize venipuncture episodes.
      The study blood sample results will test for: anti-Xa level , which is a marker of the
      effective prophylactic range of Enoxaparin, serum creatinine, which is a marker of kidney
      function and renal clearance of medication, and also for coagulation analysis (using TEG) to
      assess the coagulation effects of enoxaparin. TEG is a point-of-care device which measures
      the viscoelastic properties of clot formation. This device can provide rapid and detailed
      information about coagulation changes. The anti-XA level sample results will be blinded to
      the medical care providers and to the patient, and used for research purposes only. At or
      shortly after the patient reaches 36 weeks gestation, she will be switched from enoxaparin to
      unfractionated heparin (UFH), as per standard of care to avoid any potentially unexpected
      bleeding events associated with the onset of labor at term. When the patient comes to the
      hospital for Labor and Delivery, routine labor and delivery care will ensue at the discretion
      of the medical care team. 24 hours after delivery, or at the discretion of the medical care
      team, the patient will be restarted on her Enoxaparin dosing arm, as per standard of care.
      She will be instructed to continue the enoxaparin for 6 weeks, and will receive a
      prescription from the in-hospital providers for this. The patient will return for a 6 week
      follow-up visit in the clinic as per standard of care, and a final study blood draw will be
      performed at that time.

      If the patient misses her 6 week appointment, she will receive a phone call to reschedule as
      per standard of care, and will be instructed over the phone to discontinue her Enoxaparin and
      to come in for a blood draw.
    

Intervention name(s): Enoxaparin
Intervention type(s): Drug
Intervention description(s): Drug: Enoxaparin 40 mg every morning until 36 weeks gestation. Drug: Enoxaparin 1 mg per kg every morning until 36 weeks gestation. Dose will increase at wt. increases.
Drug: Enoxaparin dose taken by patient when enrolled until 36 weeks gestation.
Intervention MeSH terms: Enoxaparin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention