Anti Xa Monitoring Low Molecular Weight Heparin on Prevention of Venous Thromboembolism

April 2, 2023 updated by: Xuanwu Hospital, Beijing

Effect of Anti Xa Monitoring Low Molecular Weight Heparin (LMWH) on Prevention of Venous Thromboembolism in Critically Ill Patients：A Randomized Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

858

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100053
        • Recruiting
        • Xuanwu Hospital, Capital Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Peak value anti-Xa group (Group A)
The peak value of anti-Xa level of this group should be remain 0.3～0.5IU/mL. This group will receive low molecular weight heparins (LMWH) 40mg, once a day for the first 3 days. And detect the peak level of anti-Xa after 4 to 6 hours after injection of the third dose of LMWH. Adjust the dose of LMWH according to the peak value of anti Xa.
Diagnostic test: Peak value anti-Xa
This group will receive low molecular weight heparins (LMWH) 40mg, once a day for the first 3 days. And detect the peak level of anti-Xa after 4 to 6 hours after injection of the third dose of LMWH. Adjust the dose of LMWH according to the peak value of anti Xa.
Experimental: Trough value anti-Xa group (Group B)
The trough value of anti-Xa level of this group should be remain 0.1～0.2IU/mL. This group will receive low molecular weight heparins (LMWH) 40mg, once a day for the first 3 days. And detect the trough level of anti-Xa after 12 hours after injection of the third dose of LMWH. Adjust the dose of LMWH according to the trough value of anti Xa.
Diagnostic test: Trough value anti-Xa
This group will receive low molecular weight heparins (LMWH) 40mg, once a day for the first 3 days. And detect the trough level of anti-Xa after 12 hours after injection of the third dose of LMWH. Adjust the dose of LMWH according to the trough value of anti Xa.
Placebo Comparator: Control group （Group C）

The control group will not detect the value of anti Xa and not adjust the dose of LMWH.

This group will receive fixed dose of low molecular weight heparins (LMWH) 40mg, once a day.
Diagnostic test: Control Group
This group will receive fixed dose of low molecular weight heparins (LMWH) 40mg, once a day. And will not detect the level of anti-Xa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of VTE
Time Frame: 14 days after randomization
VTE include symptomatic VTE or asymptomatic VTE at day 14
14 days after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of targets reached of peak value or trough value of anti Xa for the first time
Time Frame: 14 days after randomization
LMWH 40mg，once a day, 3 day later, the peak value or trough value of anti Xa for the first time
14 days after randomization
number of hemorrhage
Time Frame: 14 days after randomization
Major hemorrhage include 1)symptomatic hemorrhage in a major organ such as intracranial hemorrhage, intra spinal, intraocular, retro peritoneal, intra-articular, pericardial and muscle bleeding causing a compartment syndrome; 2)symptomatic hemorrhage causing a fall in hemoglobin of at least 2 g / dL or leading to a transfusion of at least two blood unit.
14 days after randomization
number of all cause in-hospital death
Time Frame: 14 days and in hospital
Cause and date of death
14 days and in hospital

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xuanwu Hospital, Beijing

Collaborators

Peking University First Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2022

Primary Completion (Anticipated)

December 31, 2024

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

May 15, 2022

First Submitted That Met QC Criteria

May 15, 2022

First Posted (Actual)

May 19, 2022

Study Record Updates

Last Update Posted (Actual)

April 5, 2023

Last Update Submitted That Met QC Criteria

April 2, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-2-2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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