Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer (COPPVATS)

Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer - A Randomized, Controlled Trial

The purpose of the study is:

To estimate patients with lung cancers who will undergo surgery total haemostatic / thrombotic capacity pre, per-and postoperatively.

To investigate whether prophylactic treatment with Low Molecular Weight Heparin (LMWH) affects the patient's potential hypercoagulability.

To investigate whether there are differences in patients who will undergo Video Assisted Thorascopic Surgery (VATS) or open surgery in regards of impact of the coagulation system.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Dalteparin (Fragmin®)

Detailed Description

Lung cancer is a serious and very frequent disease. For those 25% of the patients who will undergo surgery, there are two different methods of operation: either open surgery (thoracotomy) or Video Assisted Thorascopic Surgery (VATS). The latter method is increasing in use.

Patients are often prescribed heparin pre- postoperatively, but it is unclear whether this prophylactic treatment is necessary, and it has never been thoroughly investigated.

When patients receive heparin there is an increased risk of bleeding.

Furthermore, it is unclear what changes occurs in the coagulation system pre, per- and postoperatively in patients undergoing surgery for lung-cancer, and hereby it is unclear whether these patients should have some sort of medical prophylactic treatment.

By using new analysis methods in terms of Thromboelastometry, Thrombin generation and thrombocyte function analysis, hereby the total coagulation profile can be characterized and hereby estimate the risk of thrombosis and bleeding. Thereby better be able to give the right treatment for these patients.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Rigshospitalet
  • Odense, Denmark
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Undergo surgery for lung cancer with an expected lobectomy or bilobectomy
• The surgery shall be VATS (for patients in the group randomized to other low molecular weight heparin and no prophylactic)
• Willing to be randomized (VATS-patients)
• Over 18 years old.
• Able to give assigned informed consent
• Women should be prescribed secure anticonception.

Exclusion Criteria:

• Thromboembolic events within the last three months (both venous and arterial)
• Pregnant
• Lactating
• Treatment with anticoagulation therapy in terms of vitamin K antagonist or direct or indirect thrombin inhibitors (dabigatran, apixaban or rivaroxaban)
• Treatment with thrombocyte function inhibitors in terms of Clopidogrel, ASA (acetylsalicylic acid), prasugrel and ticagrelor, and no pause of minimum 5 days (7 days with regards of prasugrel) before surgery
• Allergy for LMWH

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No treatment
Experimental: Dalteparin (Fragmin®); Dalteparin (Fragmin®) 5000 IU (International Unit) once daily	Drug: Dalteparin (Fragmin®)
Other: Open surgery arm; Dalteparin (Fragmin®) 5000 IU once daily	Drug: Dalteparin (Fragmin®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboelastometry (ROTEM®)	Analysis of in-tem, ex-tem, fib-tem og hep-tem and estimation of: Clotting time (CT (sec)), propagation (MaxVel (mm*100/sec) t,MaxVel, s) og termination (maximum clot firmness (MCF)(mm*100/sec)	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombin generation	1) recalcificering, 2) activation with tissue factor 1:17,000 and estimation of Lag time [min], ETP (endogenous thrombin potential) [nM (nanomole) thrombin*minute], peak levels of thrombin generation [nM thrombin] and time to peak thrombin (ttpeak) [min].	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standard coagulation analysis	APTT (activated partial thromboplastin time), INR (International Normalized Ratio), fibrinogen, fibrin d-dimer, thrombin time, thrombocytes and Factor VIII: clot.	30 days
Thrombocyte function analysis	analysis on Multiplate®, where the thrombocyte aggregation are expressed as Aggregation unit (AU), area under curve (A*min).	30 days

Collaborators and Investigators

• Sponsor: Thomas Decker Christensen
• Investigators: Principal Investigator: Thomas D Christensen, MD, Aarhus University Hospital

Publications and helpful links

General Publications

• Christensen TD, Vad H, Pedersen S, Licht PB, Nybo M, Hornbech K, Zois NE, Hvas AM. Video-assisted Thoracoscopic surgery (VATS) lobectomy for lung cancer does not induce a procoagulant state. Thromb J. 2017 Dec 20;15:29. doi: 10.1186/s12959-017-0152-2. eCollection 2017.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: November 25, 2012
• First Submitted That Met QC Criteria: December 4, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Estimate): June 23, 2015
• Last Update Submitted That Met QC Criteria: June 22, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Surgery; Lung cancer; Bleeding; Thromboembolism
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: COPPVATS vs 1.1; 2012-002409-23 (EudraCT Number)