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Nadroparin

Nadroparin, 0.4mL, subcutaneously, qid, given by long-term

Nadroparin, 0.4mL, subcutaneously, qid, given during hospitalization

Nadroparin, long term

Nadroparin: short-term

Shengqing Li, MD, PhD

Zhihua Ruan, MD

Wei Xiong, MD

Xueqin Yang, MD

Qi Zhou, MD

Guifang Zhang, MD

Zhifen Luo, MD

Yanqiu Zhao, MD

Yanwei Guo, MD

Jie Li, MD

Fengyun Wang, MD

Cuiying Zhang, MD

Mei Yin, MD

Zhengxia Wu, MD

Zhangqin Chen, MD

Manxiang Li, MD, PhD

Yonghong Xie, MD, PhD

Xuemin Yang, MD

Yu Yao, MD

Hong Zhao, MD

Xiang Song, MD

Ping Yu, MD

Haitao Lan, MD

Yiming Reheman, MD

Kegang Jiao, MD

To compare the efficacy and safety of prophylaxis of venous thromboembolism by Nadroparin during hospitalization to long-term usage in patients with advanced lung cancer treated by chemotherapy and/or radiotherapy.

This is a prospective, multi-center, randomized and controlled study. Advanced lung cancer patients without venous thromboembolism(VTE) are included. The selected patients were randomized into A and B groups. Group A: Nadroparin given during hospitalization, 0.4mL, subcutaneously, qid; Group B: Nadroparin given by long-term, 0.4mL, subcutaneously, qid. The incidence of VTE , the risks of bleeding and overall survival in two groups of patients are studied at different time points.

Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer

Phase Ⅲ Study of Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer by Nadroparin

Shengqing Li

Consultant, Associate professor

Digestive System Diseases

Rare Diseases

Esophageal Neoplasms

Pulmonary Embolism

Venous Thrombosis

Esophageal Cancer

Yaron Shargall

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

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.

Incidence of Venous Thromboembolism in Patients Undergoing Major Esophageal Resection

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

CT pulmonary angiogram and bilateral leg Doppler ultrasound to assess evidence of PE/DVT

Multiple measurements aggregated to arrive at one reported value (e.g., number of participants with adverse events that are related to DVT and PE).

Multiple measurements used including patient characteristics, surgical details, physiological parameters, and patient-reported symptoms questionnaire.

Blood samples used to assess D-Dimer levels to investigate the role of this laboratory test as a quantifiable clinical measure of VTE risk.

McMaster University

Symptoms and General Pathology

Body Weight

Heparin

Calcium heparin

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

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.

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.

LMWH: Dalteparin

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.

Placebo

Yaron Shargall, MD, FRCSC, FCCP

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.

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.

Extended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery

Extended Low-Molecular Weight Heparin VTE Prophylaxis in the Thoracic Surgery Population, a Prospective, Randomized Controlled Study

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

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

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.

Both procedure-specific and all-cause mortality rates will be calculated

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer	NCT01980849	Lung Cancer	Nadroparin, lon... Nadroparin: sho...	18 Years - 75 Years	Air Force Military Medical University, China
Incidence of Venous Thromboembolism in Patients Undergoing Major Esophageal Resection	NCT03115541	Venous Thromboe... Thoracic Surger... Esophageal Canc...		18 Years -	McMaster University
Incidence of Venous Thromboembolism in Patients Undergoing Major Esophageal Resection	NCT03115541	Venous Thromboe... Thoracic Surger... Esophageal Canc...		18 Years -	McMaster University
Prophylaxis of Venous Thromboembolism in Advanced Lung Cancer	NCT01980849	Lung Cancer	Nadroparin, lon... Nadroparin: sho...	18 Years - 75 Years	Air Force Military Medical University, China
Extended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery	NCT02334007	Venous Thromboe... Lung Neoplasms Pulmonary Embol...	LMWH: Daltepari... Placebo	18 Years -	McMaster University

Spots Global Cancer Trial Database for venous thromboembolism prophylaxis