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

Pirogov Russian National Research Medical University

Status and phase: Terminated; Phase 4

Conditions: Venous Thromboembolism

Treatments: Drug: Escalated Enoxaparin 30 mg twice-daily after randomization; Drug: Standard Enoxaparin 40 mg once-daily before randomization; Drug: Standard Enoxaparin 40 mg once-daily after randomization; Device: Anti-embolic elastic compression stockings; Diagnostic Test: Thrombodynamic test (TD)

Study type: Interventional

Funder types: Other

Identifiers

NCT04710732

IDAHeT

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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9 participants in 2 patient groups

Control

Active Comparator group

Description:

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

Treatment:

Diagnostic Test: Thrombodynamic test (TD)

Device: Anti-embolic elastic compression stockings

Drug: Standard Enoxaparin 40 mg once-daily after randomization

Drug: Standard Enoxaparin 40 mg once-daily before randomization

Experimental

Experimental group

Description:

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

Treatment:

Diagnostic Test: Thrombodynamic test (TD)

Device: Anti-embolic elastic compression stockings

Drug: Escalated Enoxaparin 30 mg twice-daily after randomization

Drug: Standard Enoxaparin 40 mg once-daily before randomization