Venous ThromboembolismPhase 1/2NCT02334007
Extended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery
A Phase 1/2 study testing LMWH: Dalteparin in people with Venous Thromboembolism and Lung Neoplasms, run by McMaster University at 2 sites in Canada.
Trial summary
After any surgery, there is a risk of venous thromboembolism (VTE), including Deep Vein Thrombosis (DVT) in the major veins of the legs and Pulmonary Embolus (PE) in the lungs. These clots are usually prevented by the administration of low-molecular-weight heparin, a blood thinner that prevents clotting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism, Lung Neoplasms, Pulmonary Embolism
- What is being tested?
- LMWH: Dalteparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 2 sitesCanada
- Study dates
- Sep 2015to Sep 2018
- Phase
- Phase 1/2
- 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
- Patients must be at least 18 years of age.
- Patient may be of either gender.
- Patients must be diagnosed with resectable lung cancer or metastatic lung disease eligible to complete metastasectomy.
- Patients must be undergoing one of the following surgeries: segmentectomy, wedge resection, lobectomy, bilobectomy or pneumonectomy.
- Patients must be competent to understand consent documents.
Who cannot join
- All patients with known allergic or anaphylactic reaction to contrast dye, heparin or low molecular weight heparin (LMWH).
- Patients must not be under current anticoagulation for venous thromboembolism or other medical conditions.
- Patients must not have known renal impairment (defined as estimated glomerular filtration rate of less than 30ml/min/m2 as calculated by the Cockcroft-Gault method) either pre-operatively or as identified based on blood work obtained prior to the scheduled 30-day post-operative scan.
- Patients must not have known hepatic failure, with international normalized ratio (INR) of >1.5.
- Patients with history of, or ongoing liver disease, manifested as ascites or previous peritoneal tapping for ascites.
- Patients must not be pregnant or planning to become pregnant.
Show all 12Show fewer
- Patients must not have been diagnosed or treated for VTE in the past 3 months prior to surgery.
- Patients must not have a known, objectively confirmed bleeding disorder.
- Patients must not have a present or previous increase risk of haemorrhage.
- Patients must not have a history of previous heparin induced thrombocytopenia.
- Baseline platelet count <75,000 but transient, recovered thrombocytopenia associated with chemotherapy will not be a basis for exclusion.
- Patients must not have previously inserted inferior vena cava filter.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Toronto General Hospital
Toronto, Ontario, M5G 2C4
About this study
Official title: Extended Low-Molecular Weight Heparin VTE Prophylaxis in the Thoracic Surgery Population, a Prospective, Randomized Controlled Study
After any surgery, there is a risk of venous thromboembolism (VTE), including Deep Vein Thrombosis (DVT) in the major veins of the legs and Pulmonary Embolus (PE) in the lungs. These clots are usually prevented by the administration of low-molecular-weight heparin, a blood thinner that prevents clotting. In most surgical specialties like thoracic or vascular surgery, this treatment is used until patients are discharged from the hospital. However, in orthopaedic surgery, there is strong evidence that longer term preventative treatment up to 35 days after hospital discharge helps to reduce VTE occurrences. In thoracic surgery, there is an even greater risk of developing PE because of the surgical stress, the common presence of cancer and direct damage to blood vessels in the lung during surgery. Despite the potential utility, the use of extended VTE prevention has never been evaluated in the thoracic surgery population. If extended treatment prevents clots, more patients will avoid complications related to VTE. There is currently very limited information available on the incidence of venous thromboembolism (VTE) in patients undergoing lung cancer resection and the utility of extended thromboprophylaxis (ET) in this patient population. Furthermore, in contrast to patients undergoing orthopaedic surgery where ET has become standard of care, duration of thromboprophylaxis is not well defined in this patient population. Therefore, there is a clear need to systematically evaluate the effects of extended VTE prophylaxis on the incidence of VTE in the post-op population.
Read the detailed description
There is currently very limited information available on the incidence of venous thromboembolism (VTE) in patients undergoing lung cancer resection and the utility of extended thromboprophylaxis (ET) in this patient population. Furthermore, in contrast to patients undergoing orthopaedic surgery where ET has become standard of care, duration of thromboprophylaxis is not well defined in this patient population. Therefore, there is a clear need to systematically evaluate the effects of extended VTE prophylaxis on the incidence of VTE in the post-op population.
As a pilot study, the primary outcome will involve feasibility measures. The investigators aim to measure the proportion of recruitment within each centre, compliance, loss to follow-up, and tolerability of the intervention, defined as the number and severity of per-defined adverse events. The primary outcome of interest for the future full-scale trial is the 30-day incidence rate of VTE following extended 30-day prophylaxis (defined as pulmonary emboli or deep venous thromboembolism of the lower limb as detected by CT (Computed Tomography) pulmonary angiography and full leg Doppler ultrasound, respectively) following lung resection for malignancies.
The proposed pilot project is a multicenter blinded placebo-controlled randomized controlled pilot clinical trial assessing the feasibility and effectiveness of extended-duration VTE prophylaxis (30 days post-operatively) vs. short-term prophylaxis restricted to in-hospital stay with outpatient injected placebo, in patients undergoing lung resection for lung cancer or metastatic disease. All patients will receive both a peri-operative dose followed by postoperative VTE prophylaxis for the duration of their hospital stay. Those who were randomized to prolonged prophylaxis will continue the same dosage regime for an overall of 30 days, whereas the control group will receive placebo injections for the same duration of time.
- Conditions
- Venous Thromboembolism, Lung Neoplasms, Pulmonary Embolism
- Being tested
- LMWH: Dalteparin, Placebo
- Keywords
- venous thromboembolism prophylaxis, deep vein thrombosis, pulmonary embolism, lung resection, low molecular weight heparin
- Medical subject headings
- Venous Thromboembolism, Lung Neoplasms, Pulmonary Embolism, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LMWH: DalteparinDrug
Also called Fragmin
Dalteparin is a low-molecular weight heparin. The dosage used will be 5000 units once daily (administered as a subcutaneous injection). This is an established prophylactic dose used to prevent the incidence of VTE after surgery.
PlaceboOther
Upon hospital discharge, half of the patients will be assigned to receive saline placebo injections for up to 35 days after surgery. These injections will have no effect.
| Study group | Role | What they receive |
|---|---|---|
| LMWH: Dalteparin | Experimental | Consenting patients undergoing lung resection will receive standard postoperative thromboprophylaxis in hospital until the time of discharge. Subsequently, patients will be administered LMWH for duration of 30 days as outpatients. Receives: Drug: LMWH: Dalteparin |
| Placebo | Placebo comparator | After undergoing lung resection these patients will research standard post-op TE prophylaxis and upon discharge will be administered a placebo injection of subcutaneous saline for 30 days duration. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite primary outcome: To determine the feasibility of a full scale trial by determining the recruitment rates and loss to follow up rates
Measuring accrual rates, patient compliance, adherence to protocol, any-cause loss to follow up, tolerability of the intervention (safety), adverse events, and coordination of participating centre infrastructure
Measured: 1-1.5 years
Secondary outcomes (6)
Clinical outcome:Comparison of Incidence of DVT and PE at 30 days after surgery between control and interventional arms (Outcome will be measured by a Chest Computed Tomography (CT) scan with PE contrast protocol and a full leg doppler ultrasound)
As a pilot study, there is an insufficient number of patients to definitively calculate incidence and compare treatment arms. However, this is a key outcome and the study will seek to determine this outcome. Outcome will be measured by a Chest Computed Tomography (CT) scan with PE contrast protocol and a full leg doppler ultrasound at approximately 30 days after surgery to seek the occurrence of clots
Measured: 30 days, +/- 5 days
Occurrence of major and minor bleeding at 30 days post-surgery, +/- 5 days
Bleeding is a potential adverse event of Fragmin use. Major bleeding is defined as: Fatal bleeding OR Critical bleeding in a symptomatic area (intracranial, intraspinal, retroperitoneal, pericardial, or intramuscular with compartment syndrome) OR Bleeding causing a fall in hemoglobin level of 2g/dL or more as measured by a blood test at 30 days follow up, OR Bleeding requiring a blood transfusion of at least 2 units of packed red blood cells (excluding transfusions administered intra-operatively or 6-hrs post-operatively since these could not be impacted by post-surgical prophylaxis). Minor bleeding is defined as any bleeding episode not classified as major.
Measured: 30 days after surgery
Comparison of mortality within 90 days of surgery between control and interventional arms
Both procedure-specific and all-cause mortality rates will be calculated
Measured: 90 days
Number of cases of heparin administration related HIT (Heparin Induced Thrombocytopenia) within 90 days of surgery
Measured: 90 days
Number of participants with study-related adverse events within 90 days of surgery
Measured: 90 days
Comparison of non-DVT-associated PE events (those occurring without an antecedent DVT) between control and interventional arms
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 posted8 Jan 2015 (estimated)
- Study startSep 2015
- Primary completionSep 2018
- Study completionSep 2018
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 Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yaron Shargall, MD, FRCSC, FCCP, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02334007
- Sponsor's protocol ID
- SJHH_VTEpro001
- Status last verified
- Sep 2018
- First submitted
- 18 Dec 2014
- Last updated
- 18 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Fahim C, Hylton D, Simunovic M, Agzarian J, Finley C, Hanna WC, Shargall Y. Development of the IRIS-AR strategy: an intervention to improve rates of accrual and retention for the VTE-PRO randomized controlled trial. Trials. 2019 Jul 19;20(1):447. doi: 10.1186/s13063-019-3536-8.
PubMed 31324209
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extended Low-Molecular Weight Heparin VTE Prophylaxis in the Thoracic Surgery Population, a Prospective, Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT02334007
- Acronym / sponsor ID
- SJHH_VTEpro001
- Conditions
- Venous Thromboembolism, Lung Neoplasms, Pulmonary Embolism
- Keywords
- venous thromboembolism prophylaxis, deep vein thrombosis, pulmonary embolism, lung resection, low molecular weight heparin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 8 Jan 2015 (estimated)
- 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.
After any surgery, there is a risk of venous thromboembolism (VTE), including Deep Vein Thrombosis (DVT) in the major veins of the legs and Pulmonary Embolus (PE) in the lungs. These clots are usually prevented by the administration of low-molecular-weight heparin, a blood thinner that prevents clotting. In most surgical specialties like thoracic or vascular surgery, this treatment is used until patients are discharged from the hospital. However, in orthopaedic surgery, there is strong evidence that longer term preventative treatment up to 35 days after hospital discharge helps to reduce VTE occurrences. In thoracic surgery, there is an even greater risk of developing PE because of the surgical stress, the common presence of cancer and direct damage to blood vessels in the lung during surgery. Despite the potential utility, the use of extended VTE prevention has never been evaluated in the thoracic surgery population. If extended treatment prevents clots, more patients will avoid complications related to VTE. There is currently very limited information available on the incidence of venous thromboembolism (VTE) in patients undergoing lung cancer resection and the utility of extended thromboprophylaxis (ET) in this patient population. Furthermore, in contrast to patients undergoing orthopaedic surgery where ET has become standard of care, duration of thromboprophylaxis is not well defined in this patient population. Therefore, there is a clear need to systematically evaluate the effects of extended VTE prophylaxis on the incidence of VTE in the post-op population.
Detailed description
There is currently very limited information available on the incidence of venous thromboembolism (VTE) in patients undergoing lung cancer resection and the utility of extended thromboprophylaxis (ET) in this patient population. Furthermore, in contrast to patients undergoing orthopaedic surgery where ET has become standard of care, duration of thromboprophylaxis is not well defined in this patient population. Therefore, there is a clear need to systematically evaluate the effects of extended VTE prophylaxis on the incidence of VTE in the post-op population.
As a pilot study, the primary outcome will involve feasibility measures. The investigators aim to measure the proportion of recruitment within each centre, compliance, loss to follow-up, and tolerability of the intervention, defined as the number and severity of per-defined adverse events. The primary outcome of interest for the future full-scale trial is the 30-day incidence rate of VTE following extended 30-day prophylaxis (defined as pulmonary emboli or deep venous thromboembolism of the lower limb as detected by CT (Computed Tomography) pulmonary angiography and full leg Doppler ultrasound, respectively) following lung resection for malignancies.
The proposed pilot project is a multicenter blinded placebo-controlled randomized controlled pilot clinical trial assessing the feasibility and effectiveness of extended-duration VTE prophylaxis (30 days post-operatively) vs. short-term prophylaxis restricted to in-hospital stay with outpatient injected placebo, in patients undergoing lung resection for lung cancer or metastatic disease. All patients will receive both a peri-operative dose followed by postoperative VTE prophylaxis for the duration of their hospital stay. Those who were randomized to prolonged prophylaxis will continue the same dosage regime for an overall of 30 days, whereas the control group will receive placebo injections for the same duration of time.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LMWH: Dalteparin | Experimental | Drug: LMWH: DalteparinConsenting patients undergoing lung resection will receive standard postoperative thromboprophylaxis in hospital until the time of discharge. Subsequently, patients will be administered LMWH for duration of 30 days as outpatients. |
| Placebo | Placebo comparator | Other: PlaceboAfter undergoing lung resection these patients will research standard post-op TE prophylaxis and upon discharge will be administered a placebo injection of subcutaneous saline for 30 days duration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients must be at least 18 years of age.
- Patient may be of either gender.
- Patients must be diagnosed with resectable lung cancer or metastatic lung disease eligible to complete metastasectomy.
- Patients must be undergoing one of the following surgeries: segmentectomy, wedge resection, lobectomy, bilobectomy or pneumonectomy.
- Patients must be competent to understand consent documents.
Key exclusion criteria (12 listed)
- All patients with known allergic or anaphylactic reaction to contrast dye, heparin or low molecular weight heparin (LMWH).
- Patients must not be under current anticoagulation for venous thromboembolism or other medical conditions.
- Patients must not have known renal impairment (defined as estimated glomerular filtration rate of less than 30ml/min/m2 as calculated by the Cockcroft-Gault method) either pre-operatively or as identified based on blood work obtained prior to the scheduled 30-day post-operative scan.
- Patients must not have known hepatic failure, with international normalized ratio (INR) of >1.5.
- Patients with history of, or ongoing liver disease, manifested as ascites or previous peritoneal tapping for ascites.
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 |
|---|---|---|
| LMWH: DalteparinAlso: FragminDalteparin is a low-molecular weight heparin. The dosage used will be 5000 units once daily (administered as a subcutaneous injection). This is an established prophylactic dose used to prevent the incidence of VTE after surgery. | Drug | LMWH: Dalteparin |
| PlaceboUpon hospital discharge, half of the patients will be assigned to receive saline placebo injections for up to 35 days after surgery. These injections will have no effect. | Other | Placebo |
Primary outcome
Composite primary outcome: To determine the feasibility of a full scale trial by determining the recruitment rates and loss to follow up rates
Time frame: 1-1.5 years
Measuring accrual rates, patient compliance, adherence to protocol, any-cause loss to follow up, tolerability of the intervention (safety), adverse events, and coordination of participating centre infrastructure
6 secondary outcomes
Clinical outcome:Comparison of Incidence of DVT and PE at 30 days after surgery between control and interventional arms (Outcome will be measured by a Chest Computed Tomography (CT) scan with PE contrast protocol and a full leg doppler ultrasound)
Time frame: 30 days, +/- 5 days
Occurrence of major and minor bleeding at 30 days post-surgery, +/- 5 days
Time frame: 30 days after surgery
Comparison of mortality within 90 days of surgery between control and interventional arms
Time frame: 90 days
Number of cases of heparin administration related HIT (Heparin Induced Thrombocytopenia) within 90 days of surgery
Time frame: 90 days
Number of participants with study-related adverse events within 90 days of surgery
Time frame: 90 days
Comparison of non-DVT-associated PE events (those occurring without an antecedent DVT) between control and interventional arms
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
- Derived from this study: PubMed 31324209Fahim C, Hylton D, Simunovic M, Agzarian J, Finley C, Hanna WC, Shargall Y. Development of the IRIS-AR strategy: an intervention to improve rates of accrual and retention for the VTE-PRO randomized controlled trial. Trials. 2019 Jul 19;20(1):447. doi: 10.1186/s13063-019-3536-8.
- 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.
Yaron Shargall, MD, FRCSC, FCCP principal investigator
McMaster University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LMWH: Dalteparin in people with Venous Thromboembolism and Lung Neoplasms, run by McMaster University at 2 sites in Canada.
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 12 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: finished, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Composite primary outcome: To determine the feasibility of a full scale trial by determining the recruitment rates and loss to follow up rates (time frame: 1-1.5 years). 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 NCT02334007, 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 Sep 2018.