None listed
Conditions
Brief summary
Our study will establish whether weight-based dosing of enoxaparin (for venous thromboembolism prevention) is feasible. Feasibility will be determined by the observation of peak levels of a biomarker outcome (anti-Xa) within the target ranges for VTE prophylaxis recommended for ICU patients. On completion of the study we expect to inform a future (larger, multi-centre) trial for one of the most common treatments in ICU, VTE prophylaxis in critically ill patients weighing greater than or equal to 100kg. We will also gain valuable insights into how the electronic medical record can be utilized for research on campus. Patients assigned to usual care (control) will receive enoxaparin 40mg subcutaneously twice daily. Patients assigned to the intervention arm will receive enoxaparin according to a personalized algorithm. We have reviewed the literature and based on existing data, a weight-based dosing regimen with dynamic adjustment (personalized approach) is recommended when the pharmacodynamics and pharmacokinetics of enoxaparin become unpredictable. Patients with increased body weight during critical illness represents the archetypal condition that would benefit from such an approach; it has the greatest potential to improve VTE prevention in this cohort.
Interventions
The intervention treatment offers an alternative approach to the dosing regimen of venous thromboembolism (VTE) chemoprophylaxis. Patients assigned to the intervention arm will
receive enoxaparin according to a personalized algorithm based on the patient's body weight and guided by the anti-Xa levels.
The weight-based dosing with dynamic adjustment regimen will be as follows:
1.) Enoxaparin initial dosing will be based on patient's body weight at ICU admission (~0.5mg/kg twice daily).
If a patie
The intervention treatment offers an alternative approach to the dosing regimen of venous thromboembolism (VTE) chemoprophylaxis. Patients assigned to the intervention arm will receive enoxaparin according to a personalized algorithm based on the patient's body weight and guided by the anti-Xa levels. The weight-based dosing with dynamic adjustment regimen will be as follows: 1.) Enoxaparin initial dosing will be based on patient's body weight at ICU admission (~0.5mg/kg twice daily). If a patient weighs 100-119kg, the initial dose will be 50 mg subcutaneously (SC) twice daily. If a patient weighs 120-139kg, the initial dose will be 60 mg SC twice daily. If a patient weighs 140-159kg, the initial dose will be 70 mg SC twice daily. If a patient weighs 160-179kg, the initial dose will be 80 mg SC twice daily. If a patient weighs 180kg, the initial dose will be 90 mg SC twice daily. Adherence to the intervention will be monitored through the patients' electronic medical record. 2.) The peak anti-Xa level will be determined from a blood sample drawn 4 hours after the third dose has been administered. 3.) Enoxaparin dose will be adjusted according to the anti-Xa level. If the peak anti-Xa level is below 0.2 IU/mL, the dose will be increased by 10mg SC twice daily. If the peak anti-Xa level is between 0.2 - 0.4 IU/mL, the dose will not change as this is the recommended prophylactic range for peak anti-Xa levels. If the peak anti-Xa level is between 0.41 - 0.59 IU/mL, the dose will be decreased by 10mg SC twice daily. If the peak anti-Xa level is equal to or greater than 0.6 IU/mL, the dose will be decreased by 20mg SC twice daily. 120mg SC twice daily will be the maximum dose administered. 4.) The anti-Xa assay will be repeated for every three doses of enoxaparin administered. The total duration of administration will be 28 days from randomization provided that patient is still in ICU and remains eligible for the study. If a patient meets one of the following, they are no longer eligible for the study, therefore the administration of the study drug will cease: 1. The treating Intensivist believes a particular VTE chemoprophylaxis regimen is indicated at any stage, in which case they can override the treatment allocation and this will be recorded as a protocol violation. 2. The patient develops acute kidney injury (defined as eGFR < 30 ml/min). In such cases dosing will revert to 40 mg SC daily (or as advised by intensivist) with no further anti-Xa levels recorded 3. There is a need for therapeutic anticoagulation 4. There is no arterial or venous catheter for clinical purposes, such that blood for anti-Xa level cannot be obtained. In such cases dosing will revert to 40 mg SC twice daily. The route of administration of enoxaparin is subcutaneously (SC).
Sponsors
Royal Melbourne Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
I. Adult patients greater than or equal to 18 years of age II. Admitted to RMH ICU III. Admission weight recorded as greater than or equal to 100 kg IV. Suitable to receive VTE chemoprophylaxis with enoxaparin (a Low Weight Molecular Heparin)
Exclusion criteria
I. Renal impairment that would cause a reduction in chemoprophylaxis dosing (eGFR < 30 ml/min). II. Admitted after cardiac- neuro- or spinal surgery III. Pregnancy IV. Abnormal baseline coagulation (INR >1.5 or APTT >60 sec or platelets <50 × 109/L) V. Require therapeutic anti-coagulation VI. Treating intensivist believes either a fixed dose (40mg BD) OR weight-based dynamic adjustment dosing regimen is required for that patient. VII. Received > 3 doses of enoxaparin in this ICU admission
Outcome results
None listed