Clinical trial NCT03115541: Incidence of Venous Thromboembolism in Patients Undergoing Major Esophageal Resection
Official title: The Contemporary Significance of Deep Venous Thrombosis and Pulmonary Embolus in Patients Undergoing Esophagectomy: A Pilot Study to Evaluate the Incidence of DVT and PE After Major Esophageal Resections
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Venous Thromboembolism
Thoracic Surgery
Esophageal Cancer
Keywords: venous thromboembolism prophylaxis
deep vein thrombosis
pulmonary embolus
esophageal resection
incidence
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2017-04-14
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will involve patients undergoing esophageal resection for malignancy.

Brief summary: The purpose of this study is to determine the incidence of post-operative venous thromboembolism (VTE) in patients undergoing major esophageal resection for malignancy.

Detailed description: Venous Thromboembolism (VTE) is a common post-operative complication that can result in significant patient morbidity, mortality and health care resource utilization to treat the resultant Pulmonary Embolus (PE) or Deep Vein Thrombosis (DVT) events. It is the third leading cause of cardiovascular mortality. Due to the high burden of disease, VTE events are actively prevented using mechanical and/or pharmaceutical prophylaxis interventions such as compression stockings or a variety of anti-coagulants. Extensive literature identifies incidence rates and provides guidelines regarding the use of prophylaxis measures in orthopaedic and oncological surgery, but the literature in thoracic surgery is sparse at best or conflicting with reported incidence of symptomatic events ranging from 5% to 14% after esophagectomy. The current practice of VTE prophylaxis in thoracic surgery includes administration of unfractionated or low molecular weight heparin (LMWH) starting in the perioperative period and finishing at patient discharge, while prolonged thromboprophylaxis in orthopaedic surgery beyond 10 to 14 days and up to 35 days has become the standard of care. Such an approach has never been tested or validated in esophageal cancer patients despite the substantial burden and high risk of VTE events in this population. There is a clear need for well-designed studies aiming to define the extent of peri-operative VTE for esophagectomy patients and additional contributing factors associated with VTE in those high risk patients in order to inform best practice patterns. The investigators hypothesize that the incidence and clinical burden of perioperative VTE events in esophagectomy patients are substantial, and that VTE significantly contributes to peri-and post-operative morbidity and mortality. Hence, it will be beneficial to explore the true incidence of VTE events and evaluate the effectiveness of extended-duration, post-discharge prophylaxis for these patients. The investigators also hypothesize that sub-groups of esophagectomy patients will be at higher risk for VTE events and therefore might benefit more from extended-duration, post-discharge prophylaxis, and perhaps from a more aggressive in-hospital regimen.

This prospective cohort study will involve patients undergoing major esophageal resection for esophageal cancer at 9 tertiary care centres across Canada, 4 centres in the USA, and 1 site in China. McMaster University at St. Joseph's Healthcare Hamilton will serve as the Coordinating Centre as well as a study site. Recruitment will commence at each site until 177 patients are enrolled via consecutive convenience sampling. After undergoing esophagectomy, all patients will receive both a peri-operative dose followed by post-operative LMWH VTE prophylaxis for the remainder of their hospital stay. As per current VTE prophylaxis guidelines, prophylaxis will be discontinued upon hospital discharge. VTE outcomes will be assessed using Computed Tomography with pulmonary angiography protocol at 30 and 90 days and bilateral venous Doppler ultrasounds at 30, 60 and 90 days after surgery. The role of D-Dimer will be investigated peri-operatively up to post-operative day (POD) 3, at hospital discharge or POD 10 (whichever is applicable), and at each imaging follow-up visit. A future second phase study will be a randomized controlled trial that will evaluate the role of extended duration thromboprophylaxis post-discharge in reducing the incidence of VTE in this patient population. The proposed prospective cohort study to evaluate the incidence of VTE needs to be conducted first, in order to optimize patient selection and determine the sample size for the subsequent randomized controlled trial.

Eligibility criteria: Inclusion Criteria:

1. Patients must be at least 18 years of age.
2. Patients may be of either gender.
3. Patients must be diagnosed with resectable esophageal cancer.
4. Patients must be undergoing an esophagectomy as either the first-line treatment or after completion of neoadjuvant therapies.
5. Patients must receive VTE prophylaxis as per local institutional guidelines
6. Patients must be competent to understand and sign consent documents.

Exclusion Criteria:

1. All patients with known allergic or anaphylactic reaction to contrast dye, heparin, or low molecular weight heparin (LMWH).
2. Patients must not be under current anticoagulation for venous thromboembolism or other medical conditions.
3. Patients must not have known renal impairment, defined as creatinine clearance value of less than 55ml/min/m2 as calculated by the Cockcroft-Gault method.
4. Patients with a history of, or ongoing liver disease, manifested as ascites or previous peritoneal tapping for ascites.
5. Patients with known hepatic insufficiency, defined as international normalized ratio (INR) \>1.5.
6. Patients must not be pregnant or planning to become pregnant.
7. Patients must not have been diagnosed or treated for VTE in the past 3 months prior to surgery.
8. Patients must not have a present or previous increased risk of haemorrhage.
9. Patients must not have known, objectively confirmed bleeding and clotting disorders such as thrombophilia, von Willebrand's disease, hemophilia or otherwise active bleeding.
10. Patients must not have a history of previous heparin-induced thrombocytopenia (HIT).
11. Platelet count must be above 75,000, but transient, recovered thrombocytopenia associated with chemotherapy will not be a basis for exclusion.
12. Patients must not have previously inserted inferior vena cava (IVC) filter.

Primary outcomes:
measure: Incidence of PE/DVT after esophageal resection for malignancies
timeFrame: post-operative 30 days
measure: Incidence of PE/DVT after esophageal resection for malignancies
timeFrame: post-operative 60 days
measure: Incidence of PE/DVT after esophageal resection for malignancies
timeFrame: post-operative 90 days
Secondary outcomes:
measure: Incidence of PE and DVT comparing open esophagectomy with minimally invasive surgery
timeFrame: post-operative 30, 60, 90 days
measure: Complications and mortality of DVT and PE post esophageal resection
timeFrame: post-operative 30, 60, 90 days
measure: Risk factors for the development of VTE post esophageal resection
timeFrame: post-operative 30, 60, 90 days
measure: Correlation between D-Dimer levels and VTE events post esophagectomy
timeFrame: post-operatively up to 3 days after surgery, at hospital discharge/post-operative day 10, and at 30, 60, 90 days after surgery
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Beijing
country: China
facility: Beijing Chao-yang Hospital, Capital Medical University
Study officials:
affiliation: McMaster University
name: Yaron Shargall
role: PRINCIPAL_INVESTIGATOR
References:
citation: De Martino RR, Goodney PP, Spangler EL, Wallaert JB, Corriere MA, Rzucidlo EM, Walsh DB, Stone DH. Variation in thromboembolic complications among patients undergoing commonly performed cancer operations. J Vasc Surg. 2012 Apr;55(4):1035-1040.e4. doi: 10.1016/j.jvs.2011.10.129. Epub 2012 Mar 10.
citation: Mukherjee D, Lidor AO, Chu KM, Gearhart SL, Haut ER, Chang DC. Postoperative venous thromboembolism rates vary significantly after different types of major abdominal operations. J Gastrointest Surg. 2008 Nov;12(11):2015-22. doi: 10.1007/s11605-008-0600-1. Epub 2008 Jul 31.