Clinical trial NCT05382481: Anti Xa Monitoring Low Molecular Weight Heparin on Prevention of Venous Thromboembolism
Official title: Effect of Anti Xa Monitoring Low Molecular Weight Heparin (LMWH) on Prevention of Venous Thromboembolism in Critically Ill Patients：A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Venous Thromboembolism
Keywords: venous thromboemboism
low molecular weight heparins
critically ill patients
anti-Xa
randomized controlled trial
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Peking University First Hospital
First posted: 2022-05-19
Enrollment: 858
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism, is a common cardiovascular disease associated with significant morbidity ranging from painful leg swelling, chest pain, shortness of breath, and even death. About 50% of all VTE events occur as a result of a current or recent hospital admission for surgery or acute medical illness. Hospital-acquired VTE is preventable, with interventions including anticoagulants and mechanical measures, including compression stockings and intermittent pneumatic compression. Prevented hospital acquired VTE is the focus of health services and the strongest hospital strategy to improve patient health in the world.

Detailed description: Low molecular weight heparins (LMWH) are commonly used injectable anticoagulants for venous thromboembolism (VTE) prophylaxis and treatment. LMWH forms an inhibitory complex with antithrombin to inactivate activated factor X (Xa). Due to the predictable pharmacokinetics and pharmacodynamics of LMWH, it is not necessary to routinely monitor anti-Xa levels. However, LMWH pharmacokinetics and pharmacodynamics may be less predictable in certain patient populations including renal impairment, obesity, malignancy, or pregnancy .

Both increased risk of bleeding and suboptimal efficacy are possible in obese patients. LMWHs distribute into lean body mass, therefore, obese patients with a lower proportion of lean body mass to adipose tissue receiving LMWH dosed according to actual body weight may achieve supratherapeutic drug concentrations which could increase bleeding risk . On the other hand, fixed-dose VTE prophylaxis regimens do not account for higher body weight associated with obesity potentially resulting in subtherapeutic drug concentrations increasing the risk for therapeutic failure.

As LMWH are primarily renally eliminated, impaired renal function can contribute to drug accumulation and increased risk of major bleeding.The prolonged LMWH monotherapy used in cancer-associated VTE treatment also raises concerns about drug accumulation and increased bleeding, especially in those with fluctuating renal function. In addition, pregnancy can potentially increase the clearance and volume of distribution of LMWH, increasing the potential for subtherapeutic anti-Xa levels. Thus, anti-Xa level assays are often performed for these specific patient populations in an attempt to provide optimal LMWH therapy.

Critically ill patients are higher risk populations of VTE and bleeding with complex conditions, for example sedation, mechanical ventilation, central venous catheter, and have severe infection, renal insufficiency/failure. So, the purpose of this RCT is to explore the effect of anti Xa monitoring LMWH in preventing VTE in critically ill patients and the optimal time of anti Xa monitoring, reduce mortality and serious adverse events.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older
* No gender limited
* Prospectively screened for risk and included if they received LMWH
* The patient or his / her legal representative is able and willing to sign the informed consent

Exclusion Criteria:

* History of hemorrhage or high risk of hemorrhage, including subarachnoid hemorrhage, cerebral hemorrhage, traumatic brain injury, blood system diseases, etc
* Severe renal insufficiency before randomization (creatinine clearance rate (CCr) \< 30mL/min)
* Expected length of ICU stay less than 3 days
* Known to be allergic to LMWH
* Pregnancy
* History of heparin induced thrombocytopenia
* Patients with iliac vein compression syndrome
* Receive non LMWH for prevention VTE according to the physician

Primary outcomes:
measure: number of VTE
timeFrame: 14 days after randomization
Secondary outcomes:
measure: number of targets reached of peak value or trough value of anti Xa for the first time
timeFrame: 14 days after randomization
measure: number of hemorrhage
timeFrame: 14 days after randomization
measure: number of all cause in-hospital death
timeFrame: 14 days and in hospital
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
Study officials:
References: