Individual Dose Adjustment of Low-molecular-weight-heparin by Thromodynamics Test. (IDAHeT)
Primary Purpose
Venous Thromboembolism
Status
Recruiting
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
Standard Enoxaparin 40 mg once-daily before randomization
Standard Enoxaparin 40 mg once-daily after randomization
Escalated Enoxaparin 30 mg twice-daily after randomization
Anti-embolic elastic compression stockings
Thrombodynamic test (TD)
Sponsored by
About this trial
This is an interventional prevention trial for Venous Thromboembolism focused on measuring deep vein thrombosis, pulmonary embolism, venous thromboembolism, caprini score, prophylaxis, low molecular weight heparin
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.
Sites / Locations
- Moscow Clinical Hospital no.24Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Control
Experimental
Arm Description
Peri-operative VTE prophylaxis with a standard once-daily dose of enoxaparin 40 mg and anti-embolic stockings
Peri-operative VTE prophylaxis with an escalated twice-daily dose of enoxaparin 30 mg and anti-embolic stockings
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
The number of patients with the reduction of any relevant parameter of the TD test by postoperative day 5
The number of patients in whom any relevant parameter of the TD test does not exceed the set threshold at control blood test on POD-5 (TD-5):
-initial velocity of clot growth (Vin) <62.5 μm / min at 12 hours after enoxaparin 30 mg injection (experimental group) or <64.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
or
-clot size (CS): <1333.5 μm at 12 hours after enoxaparin 30 mg injection (experimental group) or <1351.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
The number of patients with the reduction of all relevant parameters of the TD test by postoperative day 5
The number of patients in whom all relevant parameters of the TD test do not exceed the set threshold at control blood test on POD-5 (TD-5):
-initial velocity of clot growth (Vin) <62.5 μm / min at 12 hours after enoxaparin 30 mg injection (experimental group) and <64.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
and
-clot size (CS): <1333.5 μm at 12 hours after enoxaparin 30 mg injection (experimental group) and <1351.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
The number of patients with the normalization of every parameter of the TD test by postoperative day 5
The number of patients in whom every parameter of the TD test does not exceed the upper limit of normal at control blood test on POD-5 (TD-5):
initial velocity of clot growth (Vin) <56 μm / min, and
clot size (CS): <1200 μm, and
lag-time: >0.6 sec, and
stationary velocity of clot growth: <29 μm / min, and
clot density: <32000 c.u., and
spontaneous clots: negative.
Symptomatic and asymptomatic venous thromboembolism 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, SVT, or PE confirmed by unscheduled DUS, CTPA, or autopsy.
Symptomatic pulmonary embolism by postoperative day 10
The number of patients with symptomatic pulmonary embolism confirmed by CTPA or autopsy
Fatal pulmonary embolism by postoperative day 10
The number of patients with fatal pulmonary embolism confirmed by autopsy
Death by postoperative day 10
The number of patients who died for any reason within 10 days after surgery
Symptomatic and asymptomatic venous thromboembolism by postoperative day 30
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, SVT, or PE confirmed by appropriate medical image or autopsy within 30 days after surgery as revealed by clinical examination, the examination of medical records or telephone interview.
Death by postoperative day 30
The number of patients who died for any reason within 30 days after surgery as revealed by the telephone interview and/or examination of medical records.
Major bleeding by postoperative day 30
The number of patients with major bleeding as defined by the International Society of Thrombosis and Hemostasis occurred within 30 days after surgery as assessed by the Data Monitoring Committee.
Clinically relevant non-major bleeding by postoperative day 30
The number of patients with clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Hemostasis occurred within 30 days after surgery as assessed by the Data Monitoring Committee.
Minor bleeding by postoperative day 30
The number of patients with any other bleeding not fulfilling the criteria of major nor clinically relevant non-major bleeding that occurred within 30 days after surgery as assessed by the Data Monitoring Committee.
Full Information
NCT ID
NCT04710732
First Posted
January 9, 2021
Last Updated
February 14, 2022
Sponsor
Pirogov Russian National Research Medical University
1. Study Identification
Unique Protocol Identification Number
NCT04710732
Brief Title
Individual Dose Adjustment of Low-molecular-weight-heparin by Thromodynamics Test.
Acronym
IDAHeT
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
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Pirogov Russian National Research Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism
Keywords
deep vein thrombosis, pulmonary embolism, venous thromboembolism, caprini score, prophylaxis, low molecular weight heparin
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Peri-operative VTE prophylaxis with a standard once-daily dose of enoxaparin 40 mg and anti-embolic stockings
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Peri-operative VTE prophylaxis with an escalated twice-daily dose of enoxaparin 30 mg and anti-embolic stockings
Intervention Type
Drug
Intervention Name(s)
Standard Enoxaparin 40 mg once-daily before randomization
Intervention Description
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
Intervention Name(s)
Standard Enoxaparin 40 mg once-daily after randomization
Intervention Description
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
Intervention Name(s)
Escalated Enoxaparin 30 mg twice-daily after randomization
Intervention Description
Twice-daily subcutaneous injection (every 12 hours) of an escalated prophylactic dose of Enoxaparin 30 mg since POD 3 and until discharge
Intervention Type
Device
Intervention Name(s)
Anti-embolic elastic compression stockings
Intervention Description
Applied before or just after the surgery and used around the clock until discharge
Intervention Type
Diagnostic Test
Intervention Name(s)
Thrombodynamic test (TD)
Intervention Description
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)
Primary Outcome Measure Information:
Title
Symptomatic and asymptomatic venous thrombosis by postoperative day 10
Description
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.
Time Frame
day 10 after surgery
Secondary Outcome Measure Information:
Title
The number of patients with the reduction of any relevant parameter of the TD test by postoperative day 5
Description
The number of patients in whom any relevant parameter of the TD test does not exceed the set threshold at control blood test on POD-5 (TD-5):
-initial velocity of clot growth (Vin) <62.5 μm / min at 12 hours after enoxaparin 30 mg injection (experimental group) or <64.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
or
-clot size (CS): <1333.5 μm at 12 hours after enoxaparin 30 mg injection (experimental group) or <1351.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
Time Frame
day 5 after surgery
Title
The number of patients with the reduction of all relevant parameters of the TD test by postoperative day 5
Description
The number of patients in whom all relevant parameters of the TD test do not exceed the set threshold at control blood test on POD-5 (TD-5):
-initial velocity of clot growth (Vin) <62.5 μm / min at 12 hours after enoxaparin 30 mg injection (experimental group) and <64.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
and
-clot size (CS): <1333.5 μm at 12 hours after enoxaparin 30 mg injection (experimental group) and <1351.5 μm / min at 24 hours after enoxaparin 40 mg injection (control group)
Time Frame
day 5 after surgery
Title
The number of patients with the normalization of every parameter of the TD test by postoperative day 5
Description
The number of patients in whom every parameter of the TD test does not exceed the upper limit of normal at control blood test on POD-5 (TD-5):
initial velocity of clot growth (Vin) <56 μm / min, and
clot size (CS): <1200 μm, and
lag-time: >0.6 sec, and
stationary velocity of clot growth: <29 μm / min, and
clot density: <32000 c.u., and
spontaneous clots: negative.
Time Frame
day 5 after surgery
Title
Symptomatic and asymptomatic venous thromboembolism by postoperative day 10
Description
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, SVT, or PE confirmed by unscheduled DUS, CTPA, or autopsy.
Time Frame
day 10 after surgery
Title
Symptomatic pulmonary embolism by postoperative day 10
Description
The number of patients with symptomatic pulmonary embolism confirmed by CTPA or autopsy
Time Frame
day 10 after surgery
Title
Fatal pulmonary embolism by postoperative day 10
Description
The number of patients with fatal pulmonary embolism confirmed by autopsy
Time Frame
day 10 after surgery
Title
Death by postoperative day 10
Description
The number of patients who died for any reason within 10 days after surgery
Time Frame
day 10 after surgery
Title
Symptomatic and asymptomatic venous thromboembolism by postoperative day 30
Description
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, SVT, or PE confirmed by appropriate medical image or autopsy within 30 days after surgery as revealed by clinical examination, the examination of medical records or telephone interview.
Time Frame
day 30 after surgery
Title
Death by postoperative day 30
Description
The number of patients who died for any reason within 30 days after surgery as revealed by the telephone interview and/or examination of medical records.
Time Frame
day 30 after surgery
Title
Major bleeding by postoperative day 30
Description
The number of patients with major bleeding as defined by the International Society of Thrombosis and Hemostasis occurred within 30 days after surgery as assessed by the Data Monitoring Committee.
Time Frame
day 30 after surgery
Title
Clinically relevant non-major bleeding by postoperative day 30
Description
The number of patients with clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Hemostasis occurred within 30 days after surgery as assessed by the Data Monitoring Committee.
Time Frame
day 30 after surgery
Title
Minor bleeding by postoperative day 30
Description
The number of patients with any other bleeding not fulfilling the criteria of major nor clinically relevant non-major bleeding that occurred within 30 days after surgery as assessed by the Data Monitoring Committee.
Time Frame
day 30 after surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kirill Lobastov, PhD
Phone
+79852116331
Email
lobastov_kv@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kirill Lobastov, PhD
Organizational Affiliation
Pirogov RNRMU
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moscow Clinical Hospital no.24
City
Moscow
ZIP/Postal Code
127015
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kirill Lobastov, PhD
Phone
+7-985-211-63-31
Email
lobastov_kv@hotmail.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Individual Dose Adjustment of Low-molecular-weight-heparin by Thromodynamics Test.
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