Clinical trial NCT04710732: Individual Dose Adjustment of Low-molecular-weight-heparin by Thromodynamics Test.
Official title: Individual Dose Adjustment of Low-molecular-weight-heparin by Thromodynamics Test in Patients At Extremely High Risk of Postoperative Venous Thromboembolism.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Venous Thromboembolism
Keywords: deep vein thrombosis
pulmonary embolism
venous thromboembolism
caprini score
prophylaxis
low molecular weight heparin
Lead sponsor: Pirogov Russian National Research Medical University
Sponsor class: OTHER
First posted: 2021-01-15
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to evaluate the efficacy and safety of individual dose adjustment of low molecular weight heparin (LMWH) based on the results of the thrombodynamics test (TD) in patients at extremely high risk of postoperative venous thromboembolism (VTE).

This is a single-center, open-label, randomized clinical study with a blinded assessor for primary efficacy outcome.

Patients after elective or emergent major surgery having 10 or more Caprini scores at the baseline, who already received two subcutaneous injections of enoxaparin: 40 mg at 6-12 hours after the surgery ("key injection 1") and 40 mg at 12 hours after the previous injection ("key injection 2"), who had no VTE at the baseline, and who signed informed consent, are subjected to laboratory examination by the TD.

Blood samples are taken 12 hours after the "key injection 1" and 24 hours after the "key injection 2". If one of the relevant parameters of the TD (initial velocity of clot growth rate and clot size) exceeds the set threshold, the Caprini scores are recalculated adding 3 points for "other thrombophilic state" confirmed by the thrombodynamics. The patient may be included in the study if the new sum exceeds 13 points (initial 10 scores + additional 3 scores). Within 60 hours from the surgery, the included patients are randomly allocated to one of two groups: Experimental or Control. Patients in the Control group continue to receive the standard dose of enoxaparin 40 mg every 24 hours (once daily). In the Experimental group, the dose of enoxaparin is increased to 30 mg every 12 hours (twice daily).

Blood samples for TD are taken during the next two days at 24 hours after the administration of each daily dose of enoxaparin.

A whole leg duplex ultrasound scan (DUS) is performed in all patients during the screening period and at 7-10 days after the surgery or in case of any suspicion for deep vein thrombosis (DVT) or superficial vein thrombosis (SVT). Computed tomography pulmonary angiography (CTPA) is carried out in any clinical suspicion for pulmonary embolism (PE). An autopsy is performed in all dead patients.

The total follow-up period is 30 days. After discharge, patients are invited to the hospital for clinical examination with DUS or interviewed by phone to identify symptomatic VTE.


Eligibility criteria: Inclusion Criteria:

* performed major surgery;
* performed the key injection 1 and the key injection 2 of enoxaparin 40 mg;
* performed thrombodynamics test at 12 hours after the key injection 1 and at 24 hours after the key injection 2;
* at least one of the relevant TD parameters exceeds the set threshold: initial velocity of clot growth \>62.5 μm / min at 12 hours after the key injection 1, or initial velocity of clot growth \>64.5 μm / min at 24 hours after the key injection 2, or clot size \>1333.5 μm at 12 hours after the key injection 1, or clot size \>1351.5 μm at 24 hours after the key injection 2;
* Caprini score of 13 and higher after recalculation with the results of the TD test;
* infirmed consent is given.

Exclusion Criteria:

* 60 or more hours passed since the end of surgery;
* venous thrombosis at the baseline;
* performed partial occlusion of the inferior vena cava (plication, filter);
* indications for the use of anticoagulants in different regimen;
* high risk of bleeding;
* contraindication to anticoagulation;
* contraindication to elastic compression;
* inability for blood sampling from a peripheral vein;
* anticipated death within 5 days or less.

Primary outcomes:
measure: Symptomatic and asymptomatic venous thrombosis by postoperative day 10
timeFrame: day 10 after surgery
Secondary outcomes:
measure: The number of patients with the reduction of any relevant parameter of the TD test by postoperative day 5
timeFrame: day 5 after surgery
measure: The number of patients with the reduction of all relevant parameters of the TD test by postoperative day 5
timeFrame: day 5 after surgery
measure: The number of patients with the normalization of every parameter of the TD test by postoperative day 5
timeFrame: day 5 after surgery
measure: Symptomatic and asymptomatic venous thromboembolism by postoperative day 10
timeFrame: day 10 after surgery
measure: Symptomatic pulmonary embolism by postoperative day 10
timeFrame: day 10 after surgery
measure: Fatal pulmonary embolism by postoperative day 10
timeFrame: day 10 after surgery
measure: Death by postoperative day 10
timeFrame: day 10 after surgery
measure: Symptomatic and asymptomatic venous thromboembolism by postoperative day 30
timeFrame: day 30 after surgery
measure: Death by postoperative day 30
timeFrame: day 30 after surgery
measure: Major bleeding by postoperative day 30
timeFrame: day 30 after surgery
measure: Clinically relevant non-major bleeding by postoperative day 30
timeFrame: day 30 after surgery
measure: Minor bleeding by postoperative day 30
timeFrame: day 30 after surgery
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Moscow Clinical Hospital no.24
Study officials:
affiliation: Pirogov RNRMU
name: Kirill Lobastov, PhD
role: PRINCIPAL_INVESTIGATOR
References: