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

NCT04710732 | Terminated Phase 4 DMC

• 1 other identifier: IDAHeT
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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

Keywords

deep vein thrombosis; pulmonary embolism; venous thromboembolism; caprini score; prophylaxis; low molecular weight heparin

Outcome Measures

Primary Outcomes (1)

• Symptomatic and asymptomatic venous thrombosis by postoperative day 10

  The number of patients with a combination of asymptomatic DVT or SVT revealed by routine DUS performed by blinded assessor between 7 and 10 postoperative day and symptomatic DVT or SVT confirmed by unscheduled DUS.

  day 10 after surgery

Secondary Outcomes (12)

• The number of patients with the reduction of any relevant parameter of the TD test by postoperative day 5

  day 5 after surgery

• The number of patients with the reduction of all relevant parameters of the TD test by postoperative day 5

  day 5 after surgery

• The number of patients with the normalization of every parameter of the TD test by postoperative day 5

  day 5 after surgery

• Symptomatic and asymptomatic venous thromboembolism by postoperative day 10

  day 10 after surgery

• Symptomatic pulmonary embolism by postoperative day 10

  day 10 after surgery

Study Arms (2)

Control

ACTIVE COMPARATOR

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

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)

Experimental

EXPERIMENTAL

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

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

Interventions

Standard Enoxaparin 40 mg once-daily before randomization 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

Control; Experimental

Standard Enoxaparin 40 mg once-daily after randomization DRUG

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

Control

Escalated Enoxaparin 30 mg twice-daily after randomization DRUG

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

Experimental

Anti-embolic elastic compression stockings DEVICE

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

Control; Experimental

Thrombodynamic test (TD) 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)

Control; Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pirogov Russian National Research Medical University: lead

Study Sites (1)

Moscow Clinical Hospital no.24

Moscow, 127015, Russia

Location

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Study Officials

• Kirill Lobastov, PhD

  Pirogov RNRMU

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 9, 2021
• First Posted: January 15, 2021
• Study Start: March 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: January 31, 2024
• Last Updated: January 7, 2025

Record last verified: 2025-01

Locations

RU (1)