Individual Dose Adjustment of Low-molecular-weight-heparin by Thromodynamics Test.

NCT ID: NCT04710732

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2024-01-31

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.

Conditions

Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Control

Peri-operative VTE prophylaxis with a standard once-daily dose of enoxaparin 40 mg and anti-embolic stockings

Group Type: ACTIVE_COMPARATOR

Standard Enoxaparin 40 mg once-daily before randomization

Intervention Type: DRUG

Once-daily subcutaneous injection of a standard prophylactic dose of Enoxaparin 40 mg according to the set schedule:

• 12 hours before the surgery (if applicable) on a postoperative day -1 (POD -1)
• 6-12 hours after the surgery (key injection 1) on the surgery day (POD 0)
• 12 hours after the previous key injection 1 (key injection 2) on the POD 1
• 24 hours after the previous key injection 2 on the POD 2

Standard Enoxaparin 40 mg once-daily after randomization

Intervention Type: DRUG

Once-daily subcutaneous injection (every 24 hours) of a standard prophylactic dose of Enoxaparin 40 mg since POD 3 and until discharge

Anti-embolic elastic compression stockings

Intervention Type: DEVICE

Applied before or just after the surgery and used around the clock until discharge

Thrombodynamic test (TD)

Intervention Type: DIAGNOSTIC_TEST

Blood sampling for TD:

• 12 hours after key injection 1 (TD-12) on the POD 1
• 24 hours after key injection 2 (TD-24) on the POD 2
• 24 hours after each daily injection on the POD 4 (TD-4) and POD 5 (TD-5)

Experimental

Peri-operative VTE prophylaxis with an escalated twice-daily dose of enoxaparin 30 mg and anti-embolic stockings

Group Type: EXPERIMENTAL

Standard Enoxaparin 40 mg once-daily before randomization

Intervention Type: DRUG

Once-daily subcutaneous injection of a standard prophylactic dose of Enoxaparin 40 mg according to the set schedule:

• 12 hours before the surgery (if applicable) on a postoperative day -1 (POD -1)
• 6-12 hours after the surgery (key injection 1) on the surgery day (POD 0)
• 12 hours after the previous key injection 1 (key injection 2) on the POD 1
• 24 hours after the previous key injection 2 on the POD 2

Escalated Enoxaparin 30 mg twice-daily after randomization

Intervention Type: DRUG

Twice-daily subcutaneous injection (every 12 hours) of an escalated prophylactic dose of Enoxaparin 30 mg since POD 3 and until discharge

Anti-embolic elastic compression stockings

Intervention Type: DEVICE

Applied before or just after the surgery and used around the clock until discharge

Thrombodynamic test (TD)

Intervention Type: DIAGNOSTIC_TEST

Blood sampling for TD:

• 12 hours after key injection 1 (TD-12) on the POD 1
• 24 hours after key injection 2 (TD-24) on the POD 2
• 24 hours after each daily injection on the POD 4 (TD-4) and POD 5 (TD-5)

Interventions

Standard Enoxaparin 40 mg once-daily before randomization

Once-daily subcutaneous injection of a standard prophylactic dose of Enoxaparin 40 mg according to the set schedule:

• 12 hours before the surgery (if applicable) on a postoperative day -1 (POD -1)
• 6-12 hours after the surgery (key injection 1) on the surgery day (POD 0)
• 12 hours after the previous key injection 1 (key injection 2) on the POD 1
• 24 hours after the previous key injection 2 on the POD 2

Intervention Type: DRUG

Standard Enoxaparin 40 mg once-daily after randomization

Once-daily subcutaneous injection (every 24 hours) of a standard prophylactic dose of Enoxaparin 40 mg since POD 3 and until discharge

Intervention Type: DRUG

Escalated Enoxaparin 30 mg twice-daily after randomization

Twice-daily subcutaneous injection (every 12 hours) of an escalated prophylactic dose of Enoxaparin 30 mg since POD 3 and until discharge

Intervention Type: DRUG

Anti-embolic elastic compression stockings

Applied before or just after the surgery and used around the clock until discharge

Intervention Type: DEVICE

Thrombodynamic test (TD)

Blood sampling for TD:

• 12 hours after key injection 1 (TD-12) on the POD 1
• 24 hours after key injection 2 (TD-24) on the POD 2
• 24 hours after each daily injection on the POD 4 (TD-4) and POD 5 (TD-5)

Intervention Type: DIAGNOSTIC_TEST

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pirogov Russian National Research Medical University

OTHER

Sponsor Role: lead

Responsible Party

Kirill Lobastov

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kirill Lobastov, PhD

Role: PRINCIPAL_INVESTIGATOR

Pirogov RNRMU

Locations

Moscow Clinical Hospital no.24

Moscow, , Russia

Countries

Russia

Other Identifiers

IDAHeT

Identifier Type: -

Identifier Source: org_study_id