VTE (Venous Thromboembolism)THROMBO-PAINNCT07475910
Venous Thromboembolism and Chronic Pain After Major Limb Trauma
An observational study of VTE (Venous Thromboembolism) and Phantom Limb Pain After Amputation, run by Charitable Organisation Charitable Fund Superhumans (Co Cf Superhumans) at 1 site in Ukraine.
Trial summary
Major limb trauma is associated with a high risk of venous thromboembolism (VTE) due to systemic inflammation, endothelial injury, immobilization, and hypercoagulability. While VTE is commonly studied as a short-term complication affecting morbidity and mortality, its potential relationship with long-term pain… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- VTE (Venous Thromboembolism), Phantom Limb Pain After Amputation, Chronic Pain
- How many people
- 150 participants
- Where
- 1 siteUkraine
- Study dates
- 15 Mar 2026to 15 Mar 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: The study population will include adult patients (≥18 years) with major upper or lower limb trauma requiring surgical treatment and/or prolonged immobilization (≥72 hours). Participants will be recruited from trauma centers managing severe civilian and combat-related injuries. Eligible patients will be enrolled within 72 hours of hospital admission. The cohort will include patients with various mechanisms of injury, including blast injuries, fragmentation injuries, gunshot wounds, and other high-energy trauma. Participants will be followed prospectively for up to 6 months to evaluate the association between venous thromboembolism (VTE) and the development of persistent post-traumatic pain.
Who may be able to join
- Age ≥18 years
- Major upper or lower limb trauma
- Surgical treatment and/or immobilization ≥72 hours
- Enrollment within 72 hours of admission
- Informed consent
Who cannot join
- Pre-existing chronic pain unrelated to trauma (investigator judgment)
- Therapeutic anticoagulation prior to trauma
- Cognitive inability to complete follow-up
- Expected survival <48 hours
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Venous Thromboembolism and Chronic Pain After Major Limb Trauma: A Prospective Cohort Study
Major limb trauma is associated with a high risk of venous thromboembolism (VTE) due to systemic inflammation, endothelial injury, immobilization, and hypercoagulability. While VTE is commonly studied as a short-term complication affecting morbidity and mortality, its potential relationship with long-term pain outcomes after trauma has not been well investigated.
This prospective observational cohort study aims to evaluate whether objectively confirmed VTE is associated with an increased risk of persistent clinically significant pain after major limb trauma. Adult patients with severe upper or lower limb injuries requiring surgical treatment or prolonged immobilization will be enrolled within 72 hours of hospital admission and followed for six months.
Read more
The study will assess whether patients who develop VTE have a higher likelihood of persistent pain compared with those without VTE. In addition, the study will explore the association between baseline VTE risk (using the Trauma Embolic Scoring System, TESS), thromboprophylaxis timing, and long-term pain outcomes. Secondary analyses will evaluate neuropathic pain symptoms, pain interference with daily activities, quality of life, opioid consumption, and functional recovery.
Understanding the relationship between thromboembolic complications and persistent pain may help improve risk stratification, optimize thromboprophylaxis strategies, and support early rehabilitation planning in patients with major limb trauma.
Read the detailed description
Major limb trauma triggers a complex cascade of physiological responses, including systemic inflammation, endothelial injury, activation of coagulation pathways, and prolonged immobilization. These processes significantly increase the risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. VTE is a well-recognized complication following severe trauma and orthopedic injury and is typically studied in relation to acute morbidity and mortality.
However, the potential relationship between thromboembolic events and long-term pain outcomes has not been systematically investigated. Several biological mechanisms suggest a possible link between VTE and persistent post-traumatic pain. These mechanisms may include microvascular dysfunction and tissue hypoperfusion, persistent inflammatory activation, impaired rehabilitation due to thromboembolic complications, and amplification of peripheral and central sensitization pathways. These processes may contribute to prolonged nociceptive and neuropathic pain after trauma.
Patients with major limb trauma are also at risk for long-term functional impairment and chronic pain syndromes. Persistent post-traumatic pain may significantly affect rehabilitation, quality of life, and return to daily activities. Identifying early predictors of pain chronicity is therefore essential for improving long-term outcomes in trauma populations.
This prospective observational cohort study will investigate whether objectively confirmed VTE is independently associated with the development of persistent clinically significant pain following major limb trauma. Adult patients with severe upper or lower limb injuries requiring surgical treatment or prolonged immobilization will be enrolled within 72 hours of hospital admission.
VTE will be defined as objectively confirmed deep vein thrombosis diagnosed by compression ultrasonography or pulmonary embolism confirmed by CT pulmonary angiography or ventilation-perfusion imaging. VTE events occurring during hospitalization or within 30 days after injury will be included in the exposure assessment.
Baseline VTE risk will be assessed using the Trauma Embolic Scoring System (TESS), which incorporates patient age, injury severity score, obesity status, ventilator days, and presence of lower extremity fracture. This will allow evaluation of whether baseline thromboembolic risk is associated with long-term pain outcomes.
Participants will be followed prospectively for six months after injury. Pain intensity will be measured using the Numeric Rating Scale (NRS), while neuropathic pain symptoms will be assessed using the DN4 questionnaire. Pain interference with daily activities will be evaluated using the Brief Pain Inventory (BPI), and health-related quality of life will be measured using the EQ-5D-5L instrument. Additional outcomes will include opioid consumption and markers of functional recovery, including time to independent mobilization.
Statistical analyses will include descriptive statistics for baseline characteristics and comparisons between patients with and without VTE. Multivariable logistic regression models will be used to identify independent predictors of persistent pain at 3 and 6 months, adjusting for potential confounders such as injury severity, surgical interventions, baseline pain intensity, and suspected nerve injury.
By clarifying the relationship between thromboembolic complications and persistent post-traumatic pain, this study may contribute to improved risk stratification and guide integrated clinical strategies for thromboprophylaxis, pain prevention, and rehabilitation in patients with major limb trauma.
- Conditions
- VTE (Venous Thromboembolism), Phantom Limb Pain After Amputation, Chronic Pain, Chronic Pain Due to Injury
- Keywords
- Venous thromboembolism, Post-traumatic chronic pain, Neuropathic pain, Major limb trauma, Trauma Embolic Scoring System (TESS)
- Medical subject headings
- Venous Thromboembolism, Chronic Pain, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Major Limb Trauma Cohort | Adult patients with major upper or lower limb trauma requiring surgical treatment and/or prolonged immobilization (≥72 hours). Participants will be enrolled within 72 hours of admission and followed prospectively for 6 months to evaluate the association between venous thromboembolism (VTE) and persistent post-traumatic pain. VTE events will be identified during hospitalization or within 30 days after injury using standard diagnostic imaging. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Persistent Clinically Significant Pain After Major Limb Trauma
Persistent pain defined as Numeric Rating Scale (NRS) ≥4 during movement or functional activity at 3 or 6 months after injury. Pain intensity will be assessed using the standardized 0-10 Numeric Rating Scale during follow-up evaluations.
Measured: 3 months and 6 months after injury
Secondary outcomes (2)
Neuropathic Pain
DN4 (Douleur Neuropathique 4 Questionnaire) will be used to assess neuropathic pain. The DN4 score ranges from 0 to 10, where higher scores indicate a greater likelihood of neuropathic pain. A score of ≥4 is considered indicative of neuropathic pain.
Measured: 6 weeks, 3 months, and 6 months after injury.
Opioid Consumption
Total opioid consumption during follow-up expressed as oral morphine equivalent dose (OME/day).
Measured: Time Frame: up to 6 months after injury.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2026
- Study start15 Mar 2026 (estimated)
- Primary completion15 Mar 2026 (estimated)
- Study completion15 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for VTE (Venous Thromboembolism)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charitable Organisation Charitable Fund Superhumans (Co Cf Superhumans)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dmytro Dmytriiev, Charitable Organisation Charitable Fund Superhumans (Co Cf Superhumans)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07475910
- Sponsor's protocol ID
- 1303v03032026
- Other IDs
- Superhumans war trauma center
- Acronym
- THROMBO-PAIN
- Status last verified
- Mar 2026
- First submitted
- 13 Mar 2026
- Last updated
- 18 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be publicly shared due to ethical, legal, and privacy considerations related to sensitive clinical data from trauma patients, including individuals with combat-related injuries. The dataset may contain potentially identifiable health information and operational details. De-identified aggregated data may be made available upon reasonable request to the study investigators and subject to approval by the institutional ethics committee and applicable data protection regulations.
Publications
Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS. Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg. 2004 Sep;240(3):490-6; discussion 496-8. doi: 10.1097/01.sla.0000137138.40116.6c.
PubMed 15319720
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Venous Thromboembolism and Chronic Pain After Major Limb Trauma: A Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT07475910
- Acronym / sponsor ID
- THROMBO-PAIN / 1303v03032026
- Conditions
- VTE (Venous Thromboembolism), Phantom Limb Pain After Amputation, Chronic Pain, Chronic Pain Due to Injury
- Keywords
- Venous thromboembolism, Post-traumatic chronic pain, Neuropathic pain, Major limb trauma, Trauma Embolic Scoring System (TESS)
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Charitable Organisation Charitable Fund Superhumans (Co Cf Superhumans)University, hospital or other
- Study start
- 15 Mar 2026 (estimated)
- Primary completion
- 15 Mar 2026 (estimated)
- Study completion
- 15 Mar 2026 (estimated)
- First posted
- 17 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Major limb trauma is associated with a high risk of venous thromboembolism (VTE) due to systemic inflammation, endothelial injury, immobilization, and hypercoagulability. While VTE is commonly studied as a short-term complication affecting morbidity and mortality, its potential relationship with long-term pain outcomes after trauma has not been well investigated.
This prospective observational cohort study aims to evaluate whether objectively confirmed VTE is associated with an increased risk of persistent clinically significant pain after major limb trauma. Adult patients with severe upper or lower limb injuries requiring surgical treatment or prolonged immobilization will be enrolled within 72 hours of hospital admission and followed for six months.
The study will assess whether patients who develop VTE have a higher likelihood of persistent pain compared with those without VTE. In addition, the study will explore the association between baseline VTE risk (using the Trauma Embolic Scoring System, TESS), thromboprophylaxis timing, and long-term pain outcomes. Secondary analyses will evaluate neuropathic pain symptoms, pain interference with daily activities, quality of life, opioid consumption, and functional recovery.
Understanding the relationship between thromboembolic complications and persistent pain may help improve risk stratification, optimize thromboprophylaxis strategies, and support early rehabilitation planning in patients with major limb trauma.
Detailed description
Major limb trauma triggers a complex cascade of physiological responses, including systemic inflammation, endothelial injury, activation of coagulation pathways, and prolonged immobilization. These processes significantly increase the risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. VTE is a well-recognized complication following severe trauma and orthopedic injury and is typically studied in relation to acute morbidity and mortality.
However, the potential relationship between thromboembolic events and long-term pain outcomes has not been systematically investigated. Several biological mechanisms suggest a possible link between VTE and persistent post-traumatic pain. These mechanisms may include microvascular dysfunction and tissue hypoperfusion, persistent inflammatory activation, impaired rehabilitation due to thromboembolic complications, and amplification of peripheral and central sensitization pathways. These processes may contribute to prolonged nociceptive and neuropathic pain after trauma.
Patients with major limb trauma are also at risk for long-term functional impairment and chronic pain syndromes. Persistent post-traumatic pain may significantly affect rehabilitation, quality of life, and return to daily activities. Identifying early predictors of pain chronicity is therefore essential for improving long-term outcomes in trauma populations.
This prospective observational cohort study will investigate whether objectively confirmed VTE is independently associated with the development of persistent clinically significant pain following major limb trauma. Adult patients with severe upper or lower limb injuries requiring surgical treatment or prolonged immobilization will be enrolled within 72 hours of hospital admission.
VTE will be defined as objectively confirmed deep vein thrombosis diagnosed by compression ultrasonography or pulmonary embolism confirmed by CT pulmonary angiography or ventilation-perfusion imaging. VTE events occurring during hospitalization or within 30 days after injury will be included in the exposure assessment.
Baseline VTE risk will be assessed using the Trauma Embolic Scoring System (TESS), which incorporates patient age, injury severity score, obesity status, ventilator days, and presence of lower extremity fracture. This will allow evaluation of whether baseline thromboembolic risk is associated with long-term pain outcomes.
Participants will be followed prospectively for six months after injury. Pain intensity will be measured using the Numeric Rating Scale (NRS), while neuropathic pain symptoms will be assessed using the DN4 questionnaire. Pain interference with daily activities will be evaluated using the Brief Pain Inventory (BPI), and health-related quality of life will be measured using the EQ-5D-5L instrument. Additional outcomes will include opioid consumption and markers of functional recovery, including time to independent mobilization.
Statistical analyses will include descriptive statistics for baseline characteristics and comparisons between patients with and without VTE. Multivariable logistic regression models will be used to identify independent predictors of persistent pain at 3 and 6 months, adjusting for potential confounders such as injury severity, surgical interventions, baseline pain intensity, and suspected nerve injury.
By clarifying the relationship between thromboembolic complications and persistent post-traumatic pain, this study may contribute to improved risk stratification and guide integrated clinical strategies for thromboprophylaxis, pain prevention, and rehabilitation in patients with major limb trauma.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Major Limb Trauma Cohort | – | –Adult patients with major upper or lower limb trauma requiring surgical treatment and/or prolonged immobilization (≥72 hours). Participants will be enrolled within 72 hours of admission and followed prospectively for 6 months to evaluate the association between venous thromboembolism (VTE) and persistent post-traumatic pain. VTE events will be identified during hospitalization or within 30 days after injury using standard diagnostic imaging. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study population will include adult patients (≥18 years) with major upper or lower limb trauma requiring surgical treatment and/or prolonged immobilization (≥72 hours). Participants will be recruited from trauma centers managing severe civilian and combat-related injuries. Eligible patients will be enrolled within 72 hours of hospital admission. The cohort will include patients with various mechanisms of injury, including blast injuries, fragmentation injuries, gunshot wounds, and other high-energy trauma. Participants will be followed prospectively for up to 6 months to evaluate the association between venous thromboembolism (VTE) and the development of persistent post-traumatic pain.
Key inclusion criteria (5 listed)
- Age ≥18 years
- Major upper or lower limb trauma
- Surgical treatment and/or immobilization ≥72 hours
- Enrollment within 72 hours of admission
- Informed consent
Key exclusion criteria (4 listed)
- Pre-existing chronic pain unrelated to trauma (investigator judgment)
- Therapeutic anticoagulation prior to trauma
- Cognitive inability to complete follow-up
- Expected survival <48 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Persistent Clinically Significant Pain After Major Limb Trauma
Time frame: 3 months and 6 months after injury
Persistent pain defined as Numeric Rating Scale (NRS) ≥4 during movement or functional activity at 3 or 6 months after injury. Pain intensity will be assessed using the standardized 0-10 Numeric Rating Scale during follow-up evaluations.
2 secondary outcomes
Neuropathic Pain
Time frame: 6 weeks, 3 months, and 6 months after injury.
Opioid Consumption
Time frame: Time Frame: up to 6 months after injury.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Results publication: PubMed 15319720Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS. Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg. 2004 Sep;240(3):490-6; discussion 496-8. doi: 10.1097/01.sla.0000137138.40116.6c.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be publicly shared due to ethical, legal, and privacy considerations related to sensitive clinical data from trauma patients, including individuals with combat-related injuries. The dataset may contain potentially identifiable health information and operational details. De-identified aggregated data may be made available upon reasonable request to the study investigators and subject to approval by the institutional ethics committee and applicable data protection regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of VTE (Venous Thromboembolism) and Phantom Limb Pain After Amputation, run by Charitable Organisation Charitable Fund Superhumans (Co Cf Superhumans) at 1 site in Ukraine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dmytro Dmitriy Dmytriiev, PhD.Professor (+380674309449, d.dmytriiev@superhumans.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Persistent Clinically Significant Pain After Major Limb Trauma (time frame: 3 months and 6 months after injury). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07475910, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.