Study to Evaluate Weight-Based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
Information source: University of Utah
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Obesity; Venous Thrombosis; Anticoagulants
Intervention: Enoxaparin 0.5 mg/kg once daily (Drug)
Phase: Phase 4
Sponsored by: University of Utah
Official(s) and/or principal investigator(s):
Robert C Pendleton, MD, Principal Investigator, Affiliation: University of Utah
Deep vein thrombosis(DVT) is a common complication in hospitalized medical patients.
Consensus guidelines recommend using medications such as heparin or low-molecular-weight
heparins (LMWH) to prevent DVT in these patients. Generally, these medications are given in a
fixed dose that is the same for everyone. The appropriate dose of medication in patients with
severe obesity is uncertain. There is some evidence that the use of standard fixed-doses in
severely obese patients may not provide adequate protection against DVT. The purpose of this
study is to evaluate a weight-based dose(0. 5 milligrams per kilogram of body weight) of the
commonly prescribed LMWH, enoxaparin in severely obese patients to determine if predictable
levels of blood thinning can be achieved. We hypothesize that dosing enoxaparin 0. 5mg/kg once
daily in severely obese patients will lead to predictable blood levels.
Official title: Venous Thromboembolism Prevention in the Morbidly Obese Medically Ill Patient: A Pharmacological Analysis of the Predictability of Prophylactic Weight-Based Enoxaparin Dosing.
Study design: Prevention, Open Label, Single Group Assignment, Pharmacokinetics Study
Primary outcome: Peak low molecular weight heparin anti-Xa activity level.
Secondary outcome: Clinically relevant bleeding
Background and Introduction:
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in
hospitalized patients. It is a well-known complication in patients after major surgery or
trauma. More recently, medically ill patients have been identified as another high risk
group with up to 15% of patients experiencing VTE in the absence of prophylaxis. 1 Several
studies have found the use of enoxaparin, dalteparin, and fondaparinux to be safe and
effective in reducing risk of VTE by 45% to 63% in medically ill patients. 1-3 Additionally,
enoxaparin has been found to be at least as safe and effective as unfractionated heparin for
VTE prophylaxis. 4 Enoxaparin 40 mg once daily has been shown to be a safe and effective
prophylactic therapy in hospitalized patients. 1
In thromboprophylaxis studies, including those investigating enoxaparin 40 mg once daily,
morbidly obese patients (greater than or equal to 35 kg/m2) have been grossly under-enrolled.
This is problematic for several reasons. First, the drug distribution is weight dependent
and therefore, anticoagulant levels will differ according to a patient's weight. 5 Secondly,
the FDA approved doses are fixed doses that do not take into account body weight. Thirdly,
obese patients are at greater risk for failure in preventing VTE and obese patients are
probably at greater risk for developing VTE. 6 Lastly, morbidly obese patients are becoming
quite common as the population as a whole is becoming more obese.
Even with this information, there are no standards of VTE prophylaxis in obese patients.
Optimal means of delivering safe and effective thromboprophylaxis in this group is unknown.
When using LMWH's, consensus recommendations have been to monitor peak anti-Xa activity
targeting a level of 0. 1-0. 2 units/mL. 5 However, many hospitals do not have access to
anti-Xa monitoring. Studies evaluating the predictability of weight-based prophylactic
dosing of tinzaparin have demonstrated that anti-Xa levels are predictably achieved and
therefore, laboratory monitoring may not be necessary with this dosing strategy. 7 However,
tinzaparin is not widely utilized in the U. S. and uncertainties remain about whether
predictable anti-Xa levels can be achieved with a weight-based prophylactic regimen using the
more commonly used drug enoxaparin. If weight-based dosing with enoxaparin is shown to result
in predictable anti-Xa activity in obese patients, the need for monitoring would be
Objectives: The primary objective is to evaluate the predictability in achieving target
anti-Xa activity levels in morbidly obese medically ill patients using weight-adjusted (0. 5
mg/kg) once daily prophylactic dose of enoxaparin. The secondary objective is to gain
information to evaluate the pharmacokinetic curve of enoxaparin in obese patients over 18
hours after the second dose.
Participant Selection Criteria: VTE risk will be evaluated with an institutionally utilized
risk stratification scheme. This risk stratification scheme which was drafted by a
multi-disciplinary panel, represents standard of care for medically ill patients at the
University of Utah.
Inclusion Criteria: Medically ill patients who are greater than 18 years of age who have a
body mass index (BMI) greater than or equal to 35 kg/m2 who are admitted to the University of
Utah Medical Center, are at risk for VTE, and are eligible for pharmacological prophylaxis as
determined by patient's provider will be consented for the study.
Exclusion Criteria: Patients who are pregnant (a urine HCG will be performed if a female of
child-bearing age is not on reliable birth control, or if otherwise clinically indicated),
are currently on therapeutic anticoagulation, have a bleeding disorder, platelet count of
less than 100,000/mL, coagulopathy, active bleeding, creatinine clearance less than 30 mL/min
(based on Cockcroft-Gault equation, and rounding serum creatinine to 1 in patients greater
than 65 years), or recent (within 14 days) stroke, surgery or trauma will be excluded.
Design: This is a single arm study enrolling consecutive eligible patients admitted to the
University of Utah Medical Center. This is a descriptive study evaluating the feasibility
and predictability of administering weight-adjusted enoxaparin (0. 5mg/kg once daily) to
achieve recommended target peak anti-Xa levels in patients at extreme body weight. The
hypothesis is that weight-adjusted prophylaxis will reliably achieve recommended target
anti-Xa levels. If so, this would obviate the future need for routine anti-Xa monitoring
using this pharmacologic regimen.
Additionally, there will also be a parallel cohort evaluating a day 2 pharmacokinetic curve
by 5-serial anti-Xa activity measurements in a subset of up to 2-3 patients in each weight
Study procedures: Consecutive eligible patients will be enrolled if informed consent is
given. Consent will be obtained in the University Hospital, mainly on the Internal Medicine
Floor. It will be obtained by the one of the study co-investigators. At least one person
who is obtaining consent will be available to consent patients any time of day and will have
adequate time to exchange information and answer questions between investigator and
The study protocol uses a VTE prevention regimen that employs rational pharmacologic
principles and is in line with published recommendations for prophylaxis in this patient
population. In consideration of having a comparator cohort group, we would consider it to be
unethical to have a cohort group receiving enoxaparin 40 mg subcutaneously once daily as a
comparator group because pharmacologic data strongly suggests that effective levels of
anticoagulation would not be achieved in this population of patients. 8 Informed consent was
felt optimal in order to allow patients to fully understand that this regimen, although it is
an acceptable standard of care, is being employed under the broader context of a study
whereby other patient data will be collected and recorded in prospective fashion. Once
informed consent is obtained, patients will begin VTE prophylaxis with enoxaparin 0. 5 mg/kg
subcutaneously once a day. Peak anti-Xa activity will be obtained in all patients through a
venipuncture 4-6 hours after the first or second dose has been given. Five milliliters of
blood will be drawn. This is the amount of blood that is needed for this laboratory test to
be performed. Baseline clinical and demographic information will be obtained and recorded on
standard case reporting forms, CRF (see Appendix B). Patients will continue prophylaxis as
deemed necessary by their attending physician through the duration of their hospital stay or
unless dictated otherwise by the patient's attending physician. Adverse events such as VTE,
bleeding event, or thrombocytopenia will be recorded during the hospital stay (see Appendix
If patients consent to do the additional testing, this will be marked on the consent form.
These patients will have anti-Xa levels drawn before the first enoxaparin dose, and then at
4h, 6h, 12h, and 18h after the second dose of enoxaparin. If the 12h anti-Xa level is
obtained and is less than 0. 05 units/mL, then the 18 hour blood test can be eliminated. The
purpose of this section is to provide us with information to evaluate the pharmacokinetic
curve of enoxaparin in obese patients over 18 hours.
Minimum age: 18 Years.
Maximum age: N/A.
- Obese patients (BMI>35kg/m2)>18 years of age admitted to medical service and
considered at increased risk for DVT and whom pharmacological prophylaxis is being
considered by treating physician.
- Currently on alternate therapeutic anticoagulant (warfarin, heparin, LMWH)
- Platelet count <100,000, CrCl <30ml/min, or coagulopathy
- recent (within 14 d) stroke, trauma, or major surgical procedure
- Active bleeding or deemed at increased bleeding risk by the investigator.
Locations and Contacts
University of Utah, Salt Lake City, Utah 84132, United States
Starting date: January 2007
Ending date: April 2008
Last updated: June 3, 2008