Venous ThromboembolismPhase 4NCT03988231
Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study
A Phase 4 study testing Receipt of enoxaparin in people with Venous Thromboembolism and Bleeding as Surgical Complication (Treatment), run by University of Utah.
Trial summary
Post-surgical bleeding is a major source of morbidity in cancer patients, and ramifications can include need for transfusion, increased length of hospital stay, unexpected return to the operating room, or even death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism, Bleeding as Surgical Complication (Treatment), Deep Venous Thrombosis
- What is being tested?
- Receipt of enoxaparin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2021to Jun 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (age≥18) patients
- Surgical procedure under general anesthesia
- Caprini score ≤6
- Expected post-operative stay will be at least 23 hours (these are the patients for whom current guidelines mandate provision of chemical prophylaxis, but for whom current clinical practice demonstrates equipoise.)
Who cannot join
- Contraindication to use of enoxaparin
- Intracranial bleeding/stroke
- Hematoma or bleeding disorder
- Heparin-induced thrombocytopenia positive
- Creatinine clearance ≤ 30mL/min
- Serum creatinine >1.6mg/dL
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- Planned epidural anesthesia
- Scheduled return to the operating room within 90 days will be a criteria for exclusion-we will only consent patients for whom a single operative procedure is scheduled to avoid interruption of post-operative anticoagulation or placebo for a second operative procedure
- Patients with platelet count <50k/uL will be excluded only with "a positive in vitro test for anti-platelet antibody in the presence of enoxaparin sodium," per the enoxaparin package insert.
About this study
Post-surgical bleeding is a major source of morbidity in cancer patients, and ramifications can include need for transfusion, increased length of hospital stay, unexpected return to the operating room, or even death. Current guidelines support that all cancer patients who require surgical procedures receive post-operative blood thinners to minimize risk for blood clots in the legs or lungs, known as venous thromboembolism (VTE), but these medications have an unfavorable risk/benefit relationship among patients at low risk for VTE. The proposed work will pilot a randomized, double blind, placebo controlled trial to critically examine the role of de-implementation of current guidelines that mandate blood thinning medications among cancer patients at low risk for VTE who require surgical procedures; the pilot trial will allow optimization of the design of a future pragmatic multicenter trial, which ultimately would maximize patient safety after surgical procedures for cancer.
Read the detailed description
Post-operative bleeding is a major source of morbidity in cancer patients who require surgery. Bleeding is a primary concern for oncology providers because of its short and long term implications, including unanticipated transfusion, increased length of hospitalization, unexpected return to the operating room, or even death. Despite these risks, current guidelines for prevention of venous thromboembolism (VTE) in surgical patients support provision of anticoagulant medications to all post-operative patients. New data shows that current practice has an unfavorable risk/benefit relationship for the majority of cancer patients who need surgery.
Cancer and need for a surgical procedure are two recognized risk factors for VTE-this has created the perception that post-operative anticoagulants are appropriate for all cancer patients. Current VTE prevention guidelines are largely geared toward the "average" cancer patient who requires surgery, based on aggregate data from large groups of surgical patients who have similar procedures. Emerging data demonstrates that the 2005 Caprini score, a patient-centric VTE risk calculator, can identify a 15-fold variation in post-operative VTE risk among the overall surgical population. Data from our National Comprehensive Cancer Network (NCCN) center support that the Caprini score is valid specifically in oncologic surgery patients, and that 50% of cancer patients have Caprini scores ≤6 with an expected 90-day VTE rate of less than one percent. Our preliminary data show that low risk Caprini ≤6 patients have a substantial increase in bleeding (3.8% vs. 1.8%) but have no demonstrable VTE risk reduction when post-operative anticoagulants are provided.
Current guidelines that mandate chemical prophylaxis for cancer patients who have surgical procedures require a strategy that has no proven benefit and may produce a bleeding-related harm. The proposed work will utilize current paradigms of individualized VTE risk stratification to identify cancer surgery patients at low risk for VTE and will examine the impact of de-implementation of chemical prophylaxis in this low risk population The investigators will conduct a randomized, double blind, placebo controlled pilot trial at the Huntsman Cancer Institute, which is an NCCN site. The trial will identify surgical patients at low risk (Caprini score ≤6) for post-operative VTE and will randomize them to standard of care (enoxaparin 40mg once daily) versus placebo for the duration of inpatient stay. The trial will generate critical, real world data from an NCCN site that quantifies patient eligibility \& patient and provider willingness to randomize as well as expected 90-day attrition and event rates. This pilot study would generate trial-specific infrastructure and experience while providing data necessary for sample size calculations for a larger pragmatic trial to fully examine the impact of chemical prophylaxis de-implementation in cancer surgery patients at low risk for VTE.
- Conditions
- Venous Thromboembolism, Bleeding as Surgical Complication (Treatment), Deep Venous Thrombosis, Pulmonary Embolism
- Being tested
- Receipt of enoxaparin, Placebo
- Medical subject headings
- Venous Thromboembolism, Venous Thrombosis, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Receipt of enoxaparinDrug
Patients will be randomized to enoxaparin 40mg once daily versus saline placebo at 8 hours after surgery and continued for the duration of inpatient stay.
PlaceboDrug
Patients will be randomized to enoxaparin 40mg once daily versus saline placebo at 8 hours after surgery and continued for the duration of inpatient stay.
| Study group | Role | What they receive |
|---|---|---|
| Enoxaparin 40mg once daily | Active comparator | All patients will have enoxaparin prophylaxis or placebo initiated at 8 hours after surgery. Prophylaxis or placebo will be provided every 24 hours and will be continued for the duration of inpatient stay. Receives: Drug: Receipt of enoxaparin |
| Placebo | Placebo comparator | All patients will have enoxaparin prophylaxis or placebo initiated at 8 hours after surgery. Prophylaxis or placebo will be provided every 24 hours and will be continued for the duration of inpatient stay. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
90-day symptomatic venous thromboembolism
Symptomatic VTE will include 1) any deep venous thrombosis event, including upper limb, lower limb, or central veins (inferior vena cava, portal vein, etc) that is confirmed with imaging including but not limited to duplex ultrasound, CT scan, or venogram and/or 2) any pulmonary embolus event that is confirmed with imaging, including but not limited to CT scan, venogram, or V/Q scan and/or 3) any autopsy-proven VTE and/or 4) 90-day mortality in which VTE cannot be excluded (eg PEA arrest with no autopsy performed).
Measured: 90 days
90-day clinically relevant bleeding
- Symptomatic or clinically overt bleeding that is associated with one or more of a) transfusion of ≥2 units of blood, b) hemoglobin decrease of >2g/dL, or c) need for reoperation or invasive intervention such as wound opening or percutaneous drainage procedure and/or
- Symptomatic or clinically overt bleeding at a critical anatomic site, including intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, or within a muscle compartment causing compartment syndrome
- Fatal bleeding, in which the bleeding event directly contributes to death or causes clinical deterioration leading to death
- In addition, we include clinically overt bleeding in which the surgeon chooses to discontinue study drug (enoxaparin versus placebo) prior to hospital discharge as a bleeding event.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2019
- Study startJul 2021 (estimated)
- Primary completionJun 2022 (estimated)
- Study completionJun 2023 (estimated)
Why it stopped: Funding was not received.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Christopher Pannucci, University of Utah
- Investigators
- Christopher Pannucci, MD MS, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03988231
- Sponsor's protocol ID
- IRB_00121324
- Status last verified
- Sep 2021
- First submitted
- 13 Jun 2019
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study
- ClinicalTrials.gov ID
- NCT03988231
- Acronym / sponsor ID
- IRB_00121324
- Conditions
- Venous Thromboembolism, Bleeding as Surgical Complication (Treatment), Deep Venous Thrombosis, Pulmonary Embolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding was not received.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jul 2021 (estimated)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 17 Jun 2019 (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.
Post-surgical bleeding is a major source of morbidity in cancer patients, and ramifications can include need for transfusion, increased length of hospital stay, unexpected return to the operating room, or even death. Current guidelines support that all cancer patients who require surgical procedures receive post-operative blood thinners to minimize risk for blood clots in the legs or lungs, known as venous thromboembolism (VTE), but these medications have an unfavorable risk/benefit relationship among patients at low risk for VTE. The proposed work will pilot a randomized, double blind, placebo controlled trial to critically examine the role of de-implementation of current guidelines that mandate blood thinning medications among cancer patients at low risk for VTE who require surgical procedures; the pilot trial will allow optimization of the design of a future pragmatic multicenter trial, which ultimately would maximize patient safety after surgical procedures for cancer.
Detailed description
Post-operative bleeding is a major source of morbidity in cancer patients who require surgery. Bleeding is a primary concern for oncology providers because of its short and long term implications, including unanticipated transfusion, increased length of hospitalization, unexpected return to the operating room, or even death. Despite these risks, current guidelines for prevention of venous thromboembolism (VTE) in surgical patients support provision of anticoagulant medications to all post-operative patients. New data shows that current practice has an unfavorable risk/benefit relationship for the majority of cancer patients who need surgery.
Cancer and need for a surgical procedure are two recognized risk factors for VTE-this has created the perception that post-operative anticoagulants are appropriate for all cancer patients. Current VTE prevention guidelines are largely geared toward the "average" cancer patient who requires surgery, based on aggregate data from large groups of surgical patients who have similar procedures. Emerging data demonstrates that the 2005 Caprini score, a patient-centric VTE risk calculator, can identify a 15-fold variation in post-operative VTE risk among the overall surgical population. Data from our National Comprehensive Cancer Network (NCCN) center support that the Caprini score is valid specifically in oncologic surgery patients, and that 50% of cancer patients have Caprini scores ≤6 with an expected 90-day VTE rate of less than one percent. Our preliminary data show that low risk Caprini ≤6 patients have a substantial increase in bleeding (3.8% vs. 1.8%) but have no demonstrable VTE risk reduction when post-operative anticoagulants are provided.
Current guidelines that mandate chemical prophylaxis for cancer patients who have surgical procedures require a strategy that has no proven benefit and may produce a bleeding-related harm. The proposed work will utilize current paradigms of individualized VTE risk stratification to identify cancer surgery patients at low risk for VTE and will examine the impact of de-implementation of chemical prophylaxis in this low risk population The investigators will conduct a randomized, double blind, placebo controlled pilot trial at the Huntsman Cancer Institute, which is an NCCN site. The trial will identify surgical patients at low risk (Caprini score ≤6) for post-operative VTE and will randomize them to standard of care (enoxaparin 40mg once daily) versus placebo for the duration of inpatient stay. The trial will generate critical, real world data from an NCCN site that quantifies patient eligibility \& patient and provider willingness to randomize as well as expected 90-day attrition and event rates. This pilot study would generate trial-specific infrastructure and experience while providing data necessary for sample size calculations for a larger pragmatic trial to fully examine the impact of chemical prophylaxis de-implementation in cancer surgery patients at low risk for VTE.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enoxaparin 40mg once daily | Active comparator | Drug: Receipt of enoxaparinAll patients will have enoxaparin prophylaxis or placebo initiated at 8 hours after surgery. Prophylaxis or placebo will be provided every 24 hours and will be continued for the duration of inpatient stay. |
| Placebo | Placebo comparator | Drug: PlaceboAll patients will have enoxaparin prophylaxis or placebo initiated at 8 hours after surgery. Prophylaxis or placebo will be provided every 24 hours and will be continued for the duration of inpatient stay. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult (age≥18) patients
- Surgical procedure under general anesthesia
- Caprini score ≤6
- Expected post-operative stay will be at least 23 hours (these are the patients for whom current guidelines mandate provision of chemical prophylaxis, but for whom current clinical practice demonstrates equipoise.)
Key exclusion criteria (9 listed)
- Contraindication to use of enoxaparin
- Intracranial bleeding/stroke
- Hematoma or bleeding disorder
- Heparin-induced thrombocytopenia positive
- Creatinine clearance ≤ 30mL/min
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Receipt of enoxaparinPatients will be randomized to enoxaparin 40mg once daily versus saline placebo at 8 hours after surgery and continued for the duration of inpatient stay. | Drug | Enoxaparin 40mg once daily |
| PlaceboPatients will be randomized to enoxaparin 40mg once daily versus saline placebo at 8 hours after surgery and continued for the duration of inpatient stay. | Drug | Placebo |
Primary outcome
90-day symptomatic venous thromboembolism
Time frame: 90 days
Symptomatic VTE will include 1) any deep venous thrombosis event, including upper limb, lower limb, or central veins (inferior vena cava, portal vein, etc) that is confirmed with imaging including but not limited to duplex ultrasound, CT scan, or venogram and/or 2) any pulmonary embolus event that is confirmed with imaging, including but not limited to CT scan, venogram, or V/Q scan and/or 3) any autopsy-proven VTE and/or 4) 90-day mortality in which VTE cannot be excluded (eg PEA arrest with no autopsy performed).
90-day clinically relevant bleeding
Time frame: 90 days
1. Symptomatic or clinically overt bleeding that is associated with one or more of a) transfusion of ≥2 units of blood, b) hemoglobin decrease of >2g/dL, or c) need for reoperation or invasive intervention such as wound opening or percutaneous drainage procedure and/or 2. Symptomatic or clinically overt bleeding at a critical anatomic site, including intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, or within a muscle compartment causing compartment syndrome 3. Fatal bleeding, in which the bleeding event directly contributes to death or causes clinical deterioration leading to death 4. In addition, we include clinically overt bleeding in which the surgeon chooses to discontinue study drug (enoxaparin versus placebo) prior to hospital discharge as a bleeding event.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Christopher Pannucci, MD MS principal investigator
University of Utah
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Receipt of enoxaparin in people with Venous Thromboembolism and Bleeding as Surgical Complication (Treatment), run by University of Utah.
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 4 inclusion and 9 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: withdrawn, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
90-day symptomatic venous thromboembolism (time frame: 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2021.