Extended Low-Molecular Weight Heparin VTE Prophylaxis in Thoracic Surgery

NCT02334007 | Completed Phase 1 DMC

• 1 other identifier: SJHH_VTEpro001
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 2

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.

Conditions

Venous Thromboembolism; Lung Neoplasms; Pulmonary Embolism

Keywords

venous thromboembolism prophylaxis; deep vein thrombosis; pulmonary embolism; lung resection; low molecular weight heparin

Outcome Measures

Primary Outcomes (1)

• 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

  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)

  30 days, +/- 5 days

• Occurrence of major and minor bleeding at 30 days post-surgery, +/- 5 days

  30 days after surgery

• Comparison of mortality within 90 days of surgery between control and interventional arms

  90 days

• Number of cases of heparin administration related HIT (Heparin Induced Thrombocytopenia) within 90 days of surgery

  90 days

• Number of participants with study-related adverse events within 90 days of surgery

  90 days

Study Arms (2)

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.

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.

Other: Placebo

Interventions

LMWH: Dalteparin DRUG

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.

Also known as: Fragmin

LMWH: Dalteparin

Placebo OTHER

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Patients must not have previously inserted inferior vena cava filter.

Sponsors & Collaborators

• McMaster University: lead

Study Sites (2)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• 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.

  PMID: 31324209 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism; Lung Neoplasms; Pulmonary Embolism; Venous Thrombosis

Interventions

Dalteparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Embolism; Thrombosis

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Yaron Shargall, MD, FRCSC, FCCP

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: January 8, 2015
• Study Start: September 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: September 18, 2018

Record last verified: 2018-09

Locations

CA (2)