Venous Thromboembolism, Venous Thrombosis
Conditions
Keywords
venous thromboembolism, deep vein thrombosis, pulmonary embolism, prevention, intermittent pneumatic compression, sequential pneumatic compression, surgery, elastic compression, low-molecular weight heparin, prophylaxis
Brief summary
The aim of the study is to evaluate efficacy and safety of venous thromboembolism prophylaxis by the combination of graduated compression stockings (GCS), standard doses of low-molecular-weight heparins (LMWH) and sequential compression device (SCD) in the mixed group of surgical patients at high and extremely high risk for venous thromboembolism.
Detailed description
Venous thromboembolism (VTE) is the most common complication after major surgery, especially in high-risk patients. But the high-risk group is inhomogeneous. Some patients included in this group have an extremely high prevalence of postoperative venous thrombosis and pulmonary embolism, in whom the standard complex prophylaxis with elastic compression and standard anticoagulation is less effective. This is particularly so, in patients having a Caprini score of 11 and more, so that at the background of standard prophylaxis postoperative DVT is 10 times higher. This group of patients needs a more effective protocol for VTE prevention. Sequential compression devices (SCD) combined with graduated elastic compression stockings (GCS) or without them were found to be effective in the prevention of VTE in high-risk patients, especially after neurosurgical interventions, even without the administration of anticoagulants. However, their efficacy in patients at extremely high risk, having 11+ Caprini scores has not been assessed yet. The aim of the current study is to evaluate efficacy and safety of VTE prophylaxis by the combination of graduated compression stockings (GCS), standard doses of low-molecular-weight heparins (LMWH) and sequential compression device (SCD) in the mixed group of surgical patients at high and extremely high risk for venous thromboembolism The expected outcome of the study is a reduction of asymptomatic postoperative venous thrombosis rate in the hospital and reduction in all VTE during 6 months after discharge.
Interventions
DEVICESCD
Intermittent pneumatic compression (IPC) with Kendall SCD™ Sequential Compression System 700 used continuously when the patient is in bed with 6-hours night interval free of compression: from 0 a.m. to 6 a.m. In the ICU SCD used continuously all day, and in surgery department - all time of bed resting. SCD used until discharge.
DEVICEGCS
Thigh-length graduated compression stockings with pressure of 18-21 mm. Hg at the ankle used all the time until discharge plus one month after discharge
DRUGLMWH
LMWH enoxaparin (Clexane) 40 mg once a day subcutaneously started on 1st or 2-5th postoperative day according to the bleeding risk and used until discharge.
Sponsors
Medtronic
Pirogov Russian National Research Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
A randomized clinical study to assess efficacy and safety of intermittent pneumatic compression device (SCD) application in combined prevention of postoperative VTE in surgical patients at high and extremely high risk receiving graduated compression stockings and early/delayed prophylactic anticoagulation with low-molecular weight heparins.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age over 40 * Major surgery undergone\* * High risk of postoperative VTE according to a National guideline\*\* * 11+ Caprini scores * Informed consent is given
Exclusion criteria
* Acute deep vein thrombosis (DVT) at baseline * Performed inferior vena cava (IVC) plication or implanted IVC filter * Regular preoperative anticoagulation * Postoperative anticoagulation needed at therapeutic doses * Absence of anticoagulation for more than 5 days after surgery * Coagulopathy (not related to Disseminated intravascular coagulation syndrome) * Thrombocytopenia * Hemorrhagic diathesis * Lower limb soft tissue infection * Ankle-brachial index \< 0.6 * Major surgery - intervention under endotracheal anesthesia with duration of more than 60 min. * In accordance with a standard stratification system, high risk of VTE group includes patients over 60 years old after major surgery and patients 40-60 years old with additional risk factors after major surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Asymptomatic Venous Thrombosis of Lower Limbs as Detected by Duplex Ultrasound | time of discharge from the hospital or death, up to 45 days | Asymptomatic deep and/or superficial vein thrombosis of lower limbs detected by duplex ultrasound performed at baseline and then every 3-5 days after surgery until discharge. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Proximal Deep Venous Thrombosis as Detected by Duplex Ultrasound | time of discharge from the hospital or death, up to 45 days | Proximal deep vein thrombosis defined as thrombus of popliteal, femoral, iliac veins and/or inferior vena cava. Detected by duplex ultrasound performed at baseline and then every 3-5 days after surgery until discharge. |
| Number of Patients With Isolated Calf Muscle Vein Thrombosis as Detected by Duplex Ultrasound | time of discharge from the hospital or death, up to 45 days | Isolated calf muscle vein thrombosis was defined as thrombosis of soleal, gastrocnemius or other calf muscle veins not extended into tibial, or peroneal, or popliteal veins. Detected by duplex ultrasound performed at baseline and then every 3-5 days after surgery until discharge. |
| Number of Patients With Pulmonary Embolism | time of discharge from the hospital or death, up to 45 days | Symptomatic pulmonary embolism (PE) that occurred during the inpatient period of treatment and confirmed by computed tomography pulmonary angiogram (CTPA) or single-photon emission computed tomography with computed tomography (SPECT/CT) or autopsy |
| Number of Patients Died From Any Reason | time of discharge from the hospital or death, up to 45 days | Inpatient postoperative mortality: number of patients died from any reason during the inpatient period of treatment |
| Number of Patients With Symptomatic and Asymptomatic VTE Events at 30 Days After Surgery | 30 days | Taking into account all VTE events: asymptomatic revealed by duplex ultrasound, symptomatic confirmed by duplex ultrasound, CTPA, SPECT/CT, autopsy in patients discharged from the hospital and still receiving inpatients care at 30 days after surgery. |
| Number of Patients Who Died From VTE at 30 Days After Surgery | 30 days | VTE related deaths that occurred during inpatients and outpatient period of treatment and were confirmed by autopsy |
| Number of Patients With Symptomatic and Asymptomatic VTE Events at 180 Days After Surgery | 180 days | Taking into account all symptomatic and asymptomatic VTE events confirmed by duplex ultrasound, CTPA, SPECT/CT, autopsy or other appropriate methods of diagnosis that occurred during the inpatient period of treatment and outpatient period of observation |
| Number of Patients Who Died From VTE at 180 Days After Surgery | 180 days | VTE related deaths that occurred during inpatients and outpatient period of treatment and were confirmed by autopsy |
| Number of Patients With Leg Skin Injury | time of discharge from the hospital or death, up to 45 days | Leg skin injury defined as any skin hyperemia, maceration, laceration, bubbles, erosion or ulceration in the zone of application for GCS and SCD on the lower limbs revealed by clinical inspection of the skin and soft tissues until discharge |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Inpatient Period of Treatment | time of discharge from the hospital or death, up to 45 days | The inpatient period of treatment suggests time from surgical intervention to discharge from the hospital or death. |
Countries
Russia
Participant flow
Recruitment details
The total amount of 812 patients were screened during the enrollment period, 405 of them were excluded: Caprini score of \<11 (n=304); a various regimen of anticoagulation (n=48); venous thrombosis at the baseline (n=31); declined participation (n=18); implanted inferior vena cava filter (n=4).
Participants by arm
| Arm | Count |
|---|---|
| Experimental Group (SCD + GCS + LMWH) Sequential Compression Device (SCD): Intermittent pneumatic compression (IPC) with Kendall SCD™ Sequential Compression System 700 used continuously when the patient is in bed with a 6-hours night interval free of compression: from 0 a.m. to 6 a.m. In the ICU SCD used continuously all day, and in the surgery department - all time of bed rest. SCD used until discharge.
Graduated Compression Stockings (GCS): Thigh-length graduated compression stockings with a pressure of 18-21 mm. Hg at the ankle used all the time until discharge plus one month after discharge
Low-Molecular-Weight Heparin: LMWH enoxaparin (Clexane) 40 mg once a day subcutaneously started on 1st or 2-5th postoperative day according to the bleeding risk and used until discharge. | 204 |
| Control Group (GCS + LMWH) GCS: Thigh-length graduated compression stockings with pressure of 18-21 mm. Hg at the ankle used all the time until discharge plus one month after discharge
LMWH: LMWH enoxaparin (Clexane) 40 mg once a day subcutaneously started on 1st or 2-5th postoperative day according to the bleeding risk and used until discharge. | 203 |
| Total | 407 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 37 | 45 |
Baseline characteristics
| Characteristic | Control Group (GCS + LMWH) | Total | Experimental Group (SCD + GCS + LMWH) |
|---|---|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 10 | 68.8 years STANDARD_DEVIATION 9.8 | 68.8 years STANDARD_DEVIATION 9.6 |
| Caprini score | 11.4 units on a scale STANDARD_DEVIATION 1.9 | 11.4 units on a scale STANDARD_DEVIATION 1.9 | 11.5 units on a scale STANDARD_DEVIATION 1.8 |
| Malignancy | 165 Participants | 336 Participants | 171 Participants |
| Number of patients with Caprini score of 11 and higher | 140 Participants | 285 Participants | 145 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Russia | 203 Participants | 407 Participants | 204 Participants |
| Sex: Female, Male Female | 118 Participants | 247 Participants | 129 Participants |
| Sex: Female, Male Male | 85 Participants | 160 Participants | 75 Participants |
| Surgical profile Addominal surgery | 147 Participants | 278 Participants | 131 Participants |
| Surgical profile Non-abdominal surgery | 56 Participants | 129 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 204 | 18 / 203 |
| other Total, other adverse events | 27 / 204 | 22 / 203 |
| serious Total, serious adverse events | 5 / 204 | 4 / 203 |
Outcome results
Primary
Number of Patients With Asymptomatic Venous Thrombosis of Lower Limbs as Detected by Duplex Ultrasound
Asymptomatic deep and/or superficial vein thrombosis of lower limbs detected by duplex ultrasound performed at baseline and then every 3-5 days after surgery until discharge.
Time frame: time of discharge from the hospital or death, up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients With Asymptomatic Venous Thrombosis of Lower Limbs as Detected by Duplex Ultrasound | 1 Participants |
| Control Group (GCS + LMWH) | Number of Patients With Asymptomatic Venous Thrombosis of Lower Limbs as Detected by Duplex Ultrasound | 34 Participants |
p-value: <0.001Fisher Exact
Secondary
Number of Patients Died From Any Reason
Inpatient postoperative mortality: number of patients died from any reason during the inpatient period of treatment
Time frame: time of discharge from the hospital or death, up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients Died From Any Reason | 6 Participants |
| Control Group (GCS + LMWH) | Number of Patients Died From Any Reason | 10 Participants |
p-value: >0.05Fisher Exact
Secondary
Number of Patients Who Died From VTE at 180 Days After Surgery
VTE related deaths that occurred during inpatients and outpatient period of treatment and were confirmed by autopsy
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients Who Died From VTE at 180 Days After Surgery | 0 Participants |
| Control Group (GCS + LMWH) | Number of Patients Who Died From VTE at 180 Days After Surgery | 3 Participants |
Secondary
Number of Patients Who Died From VTE at 30 Days After Surgery
VTE related deaths that occurred during inpatients and outpatient period of treatment and were confirmed by autopsy
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients Who Died From VTE at 30 Days After Surgery | 0 Participants |
| Control Group (GCS + LMWH) | Number of Patients Who Died From VTE at 30 Days After Surgery | 2 Participants |
Secondary
Number of Patients With Isolated Calf Muscle Vein Thrombosis as Detected by Duplex Ultrasound
Isolated calf muscle vein thrombosis was defined as thrombosis of soleal, gastrocnemius or other calf muscle veins not extended into tibial, or peroneal, or popliteal veins. Detected by duplex ultrasound performed at baseline and then every 3-5 days after surgery until discharge.
Time frame: time of discharge from the hospital or death, up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients With Isolated Calf Muscle Vein Thrombosis as Detected by Duplex Ultrasound | 1 Participants |
| Control Group (GCS + LMWH) | Number of Patients With Isolated Calf Muscle Vein Thrombosis as Detected by Duplex Ultrasound | 15 Participants |
p-value: <0.001Fisher Exact
Secondary
Number of Patients With Leg Skin Injury
Leg skin injury defined as any skin hyperemia, maceration, laceration, bubbles, erosion or ulceration in the zone of application for GCS and SCD on the lower limbs revealed by clinical inspection of the skin and soft tissues until discharge
Time frame: time of discharge from the hospital or death, up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients With Leg Skin Injury | 25 Participants |
| Control Group (GCS + LMWH) | Number of Patients With Leg Skin Injury | 15 Participants |
p-value: >0.05Fisher Exact
Secondary
Number of Patients With Proximal Deep Venous Thrombosis as Detected by Duplex Ultrasound
Proximal deep vein thrombosis defined as thrombus of popliteal, femoral, iliac veins and/or inferior vena cava. Detected by duplex ultrasound performed at baseline and then every 3-5 days after surgery until discharge.
Time frame: time of discharge from the hospital or death, up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients With Proximal Deep Venous Thrombosis as Detected by Duplex Ultrasound | 0 Participants |
| Control Group (GCS + LMWH) | Number of Patients With Proximal Deep Venous Thrombosis as Detected by Duplex Ultrasound | 5 Participants |
p-value: 0.03Fisher Exact
Secondary
Number of Patients With Pulmonary Embolism
Symptomatic pulmonary embolism (PE) that occurred during the inpatient period of treatment and confirmed by computed tomography pulmonary angiogram (CTPA) or single-photon emission computed tomography with computed tomography (SPECT/CT) or autopsy
Time frame: time of discharge from the hospital or death, up to 45 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients With Pulmonary Embolism | 0 Participants |
| Control Group (GCS + LMWH) | Number of Patients With Pulmonary Embolism | 5 Participants |
p-value: 0.03Fisher Exact
Secondary
Number of Patients With Symptomatic and Asymptomatic VTE Events at 180 Days After Surgery
Taking into account all symptomatic and asymptomatic VTE events confirmed by duplex ultrasound, CTPA, SPECT/CT, autopsy or other appropriate methods of diagnosis that occurred during the inpatient period of treatment and outpatient period of observation
Time frame: 180 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients With Symptomatic and Asymptomatic VTE Events at 180 Days After Surgery | 1 Participants |
| Control Group (GCS + LMWH) | Number of Patients With Symptomatic and Asymptomatic VTE Events at 180 Days After Surgery | 35 Participants |
p-value: <0.001Fisher Exact
Secondary
Number of Patients With Symptomatic and Asymptomatic VTE Events at 30 Days After Surgery
Taking into account all VTE events: asymptomatic revealed by duplex ultrasound, symptomatic confirmed by duplex ultrasound, CTPA, SPECT/CT, autopsy in patients discharged from the hospital and still receiving inpatients care at 30 days after surgery.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Number of Patients With Symptomatic and Asymptomatic VTE Events at 30 Days After Surgery | 1 Participants |
| Control Group (GCS + LMWH) | Number of Patients With Symptomatic and Asymptomatic VTE Events at 30 Days After Surgery | 35 Participants |
p-value: <0.001Fisher Exact
Other Pre-specified
Duration of Inpatient Period of Treatment
The inpatient period of treatment suggests time from surgical intervention to discharge from the hospital or death.
Time frame: time of discharge from the hospital or death, up to 45 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Group (SCD + GCS + LMWH) | Duration of Inpatient Period of Treatment | 10 days |
| Control Group (GCS + LMWH) | Duration of Inpatient Period of Treatment | 10 days |