Back to resultsExtended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery
Primary Purpose
Venous Thromboembolism, Lung Neoplasms, Pulmonary Embolism
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
LMWH: Dalteparin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Venous Thromboembolism focused on measuring venous thromboembolism prophylaxis, deep vein thrombosis, pulmonary embolism, lung resection, low molecular weight heparin
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- St. Joseph's Healthcare Hamilton
- Toronto General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
LMWH: Dalteparin
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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.
Comparison of mortality within 90 days of surgery between control and interventional arms
Both procedure-specific and all-cause mortality rates will be calculated
Number of cases of heparin administration related HIT (Heparin Induced Thrombocytopenia) within 90 days of surgery
Number of participants with study-related adverse events within 90 days of surgery
Comparison of non-DVT-associated PE events (those occurring without an antecedent DVT) between control and interventional arms
Full Information
NCT ID
NCT02334007
First Posted
December 18, 2014
Last Updated
September 17, 2018
Sponsor
McMaster University
1. Study Identification
Unique Protocol Identification Number
NCT02334007
Brief Title
Extended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery
Official Title
Extended Low-Molecular Weight Heparin VTE Prophylaxis in the Thoracic Surgery Population, a Prospective, Randomized Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
September 2018 (Actual)
Study Completion Date
September 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
McMaster University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism, Lung Neoplasms, Pulmonary Embolism
Keywords
venous thromboembolism prophylaxis, deep vein thrombosis, pulmonary embolism, lung resection, low molecular weight heparin
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LMWH: Dalteparin
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LMWH: Dalteparin
Other Intervention Name(s)
Fragmin
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Composite primary outcome: To determine the feasibility of a full scale trial by determining the recruitment rates and loss to follow up rates
Description
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
Time Frame
1-1.5 years
Secondary Outcome Measure Information:
Title
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)
Description
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
Time Frame
30 days, +/- 5 days
Title
Occurrence of major and minor bleeding at 30 days post-surgery, +/- 5 days
Description
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.
Time Frame
30 days after surgery
Title
Comparison of mortality within 90 days of surgery between control and interventional arms
Description
Both procedure-specific and all-cause mortality rates will be calculated
Time Frame
90 days
Title
Number of cases of heparin administration related HIT (Heparin Induced Thrombocytopenia) within 90 days of surgery
Time Frame
90 days
Title
Number of participants with study-related adverse events within 90 days of surgery
Time Frame
90 days
Title
Comparison of non-DVT-associated PE events (those occurring without an antecedent DVT) between control and interventional arms
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yaron Shargall, MD, FRCSC, FCCP
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Joseph's Healthcare Hamilton
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31324209
Citation
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.
Results Reference
derived
Learn more about this trial
Extended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery
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