Investigation Into the Therapeutic Dosage of Fondaparinux Sodium, a Medication Used to Prevent Blood Clots in Morbidly Obese Volunteers
Condition: Venous Thrombosis; Pulmonary Embolism
MeSH terms: Pulmonary Embolism; Thrombosis; Embolism; Venous Thrombosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Morbidly obese individuals are at high risk for potentially life threatening blood clots
      around the time of abdominal surgical procedures. Fondaparinux sodium (Arixtra) is an FDA-
      approved medication used in the prevention of deep venous thrombosis (DVT) at the time of
      orthopedic or abdominal surgery, as well as for the treatment of DVT and pulmonary embolism
      (PE). As with many medications, therapeutic dosages have not been fully investigated for the
      morbidly obese population. Our goal is to study the therapeutic blood levels, after 2
      different dosages of the medication are given to morbidly obese volunteers. We will recruit
      21 morbidly obese (Body Mass Index (BMI) > 35) individuals who are in the evaluation process
      for bariatric surgery. They will be divided into 7 groups: 3 participants with BMI 35 - 39.9,
      3 with a BMI of 40 - 49.9, 3 with a BMI of 50 - 59.9, 3 with a BMI > 60, 3 with a weight of
      100 - 149 KG, 3 with a weight of 150 - 199 KG and 3 with a weight of 200 - 249 KG.
      Participants will be administered two different doses of the medication with a 2-week
      interval in between, then blood will be drawn in various intervals throughout the next 48
      hours to see which dose provides the best therapeutic levels. Participants will be monitored
      closely for any side effects or complications.
    

Detailed description: 
      Bariatric surgery carries a mortality rate of 0.5-1%, with PE found to be the most frequent
      postoperative complications and causes of death. Currently employed prophylactic methods
      include unfractionated or low molecular weight heparins in combination with mechanical calf
      compression. However, despite the implementation of these standard measures, the reported
      incidence of fatal PE has ranged from 0.2 to 0.64% accounting for between 30 to 50% of deaths
      after bariatric surgery.

      With a reported 40,000 bariatric surgical procedures in 2001, and the numbers growing rapidly
      every year, there is clearly a need for a more effective prophylaxis from DVT and PE. The
      pentasaccharide fondaparinux is an anti-thrombotic agent used in the prophylaxis of venous
      thromboembolism after orthopedic or abdominal surgery. Its clinical value has been
      established in multiple randomized double blind studies in high-risk major orthopedic surgery
      where it showed a 55% greater reduction in DVT episodes compared to enoxaparin (Lovenox®)
      Although fondaparinux has been administered in obese patients in clinical studies for
      prevention of venous thromboembolism after orthopedic surgery and preliminary results show no
      influence of ABW on the clinical outcome, the pharmacokinetic properties of the drug in the
      morbidly obese have not been investigated. Previously published fondaparinux pharmacokinetic
      studies excluded patients whose body weight was more than 30% of ideal, with the heaviest
      group being 77.2+/-10.1 Kg and with a BMI of 25.7+/2.6 Kg/m2. Similar studies on low
      molecular weight heparins, such as enoxaparin and dalteparin, showed predictable anti-Xa
      activity with weight-based dosing in the morbidly obese.

      There has been no study on the pharmacokinetics of this drug in the morbidly obese (BMI>35
      Kg/m2). It is clinically imperative to have a predictable anti-Xa level and a predictable DVT
      prophylactic effect in the morbidly obese whose body weight may vary by as much as 3 to 4
      fold higher compared to the average 70 Kg adult. This has become a critical issue in view of
      the large number of bariatric surgical operations being undertaken, which has increased 150%
      in the last two years.

      The purpose of this study is to assess the pharmacokinetic properties of fondaparinux in
      morbidly obese volunteers. This is a prospective crossover, randomized study with a 2-week
      washout period comparing two dosing regimens of fondaparinux in morbidly obese volunteers.
    

Intervention name(s): Fondaparinux Sodium
Intervention type(s): Drug
Intervention MeSH terms: PENTA; Fondaparinux
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Anticoagulation Prophylaxis; Venous Thrombosis; Deep Vein Thrombosis; Pulmonary Embolism; Fondaparinux Sodium; Arixtra; Pharmakinetics