Extended Out-of-hospital Low-molecular-weight Heparin Prophylaxis Against DVT and PE in Patients Undergoing Major Lung Resection

NCT ID: NCT02258958

Last Updated: 2014-12-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2014-12-31

Brief Summary

Postoperative venous thromboembolism (VTE) is a significant health-care problem, resulting in significant morbidity, mortality and resource utilization. The true incidence is unknown, and may range from 1% to 15%. At the current time, the clinical practice of VTE prophylaxis in thoracic surgery includes administration of unfractionated or low molecular weight heparin starting at the perioperative period and finishing at the time of patients' discharge. In orthopaedic surgery, prolonged thromboprophylaxis beyond 10 days and up to 35 days has become the standard of care. There is a clear need to systematically evaluate the incidence of VTE after resection of lung malignancies and to evaluate the role of extended VTE prophylaxis in preventing Deep Vein Thrombosis (DVT) and pulmonary embolus (PE) after those major lung resections. This study will involve patients undergoing lung resection for malignancy at St. Joseph's Healthcare Hamilton and the University Health Network's Toronto General Hospital. The study will include 150 consecutively recruited patients. Study interventions will include Computed Tomography with pulmonary embolus (PE) protocol and bilateral extended leg Doppler Ultrasound for the detection of Deep Vein Thrombosis 30 days post-surgery.

In summary, this study is aimed at evaluating, for the first time in a prospective manner, the actual incidence of DVT and PE in patients undergoing major lung resections for malignancies. The knowledge gained in this study will be used to inform a future investigation involving a Randomized Controlled Trial (RCT) to compare current post-operative thromboprophylaxis with an extended 30-day prophylaxis protocol with the hope of providing an evidence-based practice change in VTE prophylaxis care for this high risk population.

Detailed Description

Postoperative venous thromboembolism (VTE) is a significant health-care problem, resulting in significant morbidity, mortality and resource utilization. The true incidence is unknown, and may range from 1% to 15%. The latest American College of Chest Physicians (ACCP) guidelines on VTE prevention clearly outlines the perioperative thromboprophylaxis regiments for specific surgical populations. Specifically for patients undergoing orthopaedic procedures, such as total hip replacement, there is strong Grade 1A evidence for the use of extended thromboprophylaxis. For other surgical subgroups such as vascular and thoracic surgery, the evidence is less clear.

Therefore at the current time, the clinical practice of VTE prophylaxis in thoracic surgery includes administration of unfractionated or low molecular weight heparin starting at the perioperative period and finishing at the time of patients' discharge. Prolonged thromboprophylaxis in orthopaedic surgery beyond 10 days and up to 35 days has become the standard of care and has Grade 1A recommendations from ACCP. This approach has never been tested or validated in thoracic surgery, where major lung resection exposes the patient to an increased VTE risk not only due to the surgical stress and existence of malignancy, but also due to direct in-situ vascular injury secondary to resection of pulmonary arterial branches during the lung resection. Hence, there is a clear need to systematically evaluate the incidence of VTE after resection of lung malignancies and to evaluate the role of extended VTE prophylaxis in preventing DVT and pulmonary embolus (PE) after those major lung resections.

The study will involve patients undergoing sub-lobar resection, lobectomy, bilobectomy or pneumonectomy for lung cancer or metastatic lung disease at St. Joseph's Healthcare Hamilton, a regional tertiary thoracic surgery program with more than 350 major lung resections performed within the institution annually, as well as the University Health Network's Toronto General Hospital. The study will evaluate the incidence of post-operative venous thromboembolism (VTE) and will include 150 consecutively recruited patients. Study interventions will include Computed Tomography with pulmonary embolus (PE) protocol and bilateral extended leg Doppler Ultrasound for the detection of Deep Vein Thrombosis 30 days post-surgery.

In summary, this study is aimed at evaluating, for the first time in a prospective manner, the actual incidence of DVT and PE in patients undergoing major lung resections for malignancies. The knowledge gained in this study will be used to inform a future investigation involving an RCT to compare current post-operative thromboprophylaxis with an extended 30-day prophylaxis protocol with the hope of providing an evidence-based practice change in VTE prophylaxis care for this high risk population.

Conditions

Venous Thrombosis; Pulmonary Embolism; Lung Neoplasms

Keywords

venous thromboembolism prophylaxis; deep venous thrombosis; pulmonary embolus; thoracic surgery; lung resection; incidence

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• At least 18 years of age
• Either gender
• Diagnosed with resectable lung cancer or metastatic lung disease eligible to complete metastasectomy
• Undergoing one of the following surgeries: Segmentectomy, wedge resection, lobectomy, bilobectomy or pneumonectomy
• Competent to understand and sign consent documents

Exclusion Criteria

• Known allergic or anaphylactic reaction to contrast dye, heparin or low molecular weight heparin (LMWH)
• Under current anticoagulation for venous thromboembolism or other medical conditions
• Known renal impairment, defined as creatinine clearance value of less than 55ml/min/m2 as calculated by the Cockroft-Gault method
• History of, or ongoing liver disease, manifested as ascites or previous peritoneal tapping for ascites
• Pregnant or planning to become pregnant
• Diagnosed or treated for VTE in the past 3 months prior to surgery
• Present or previous increase risk of haemorrhage
• History of previous HIT (heparin induced thrombocytopenia)
• Platelet count must be below 75,000
• Previously inserted Inferior Vena Cava Filter (IVC) filter.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Toronto General Hospital

OTHER

Sponsor Role: collaborator

Heart and Stroke Foundation of Canada

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Yaron Shargall

Head of Services Thoracic Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yaron Shargall, MD BSc

Role: PRINCIPAL_INVESTIGATOR

St. Joseph's Healthcare Hamilton

Locations

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Toronto General Hospital (UHN)

Toronto, Ontario, Canada

Countries

Canada

References

Comp PC, Spiro TE, Friedman RJ, Whitsett TL, Johnson GJ, Gardiner GA Jr, Landon GC, Jove M; Enoxaparin Clinical Trial Group. Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am. 2001 Mar;83(3):336-45. doi: 10.2106/00004623-200103000-00004.

Reference Type: BACKGROUND

PMID: 11263636 (View on PubMed)

Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):381S-453S. doi: 10.1378/chest.08-0656.

Reference Type: BACKGROUND

PMID: 18574271 (View on PubMed)

Daddi G, Milillo G, Lupattelli L, Ragusa M, Lemmi A, Puma F, Agnelli G; Pulmonary Embolism in Thoracic Surgery Study Group. Postoperative pulmonary embolism detected with multislice computed tomography in lung surgery for cancer. J Thorac Cardiovasc Surg. 2006 Jul;132(1):197-8. doi: 10.1016/j.jtcvs.2006.03.036. No abstract available.

Reference Type: BACKGROUND

PMID: 16798341 (View on PubMed)

Kalweit G, Huwer H, Volkmer I, Petzold T, Gams E. Pulmonary embolism: a frequent cause of acute fatality after lung resection. Eur J Cardiothorac Surg. 1996;10(4):242-6; discussion 246-7. doi: 10.1016/s1010-7940(96)80146-1.

Reference Type: BACKGROUND

PMID: 8740059 (View on PubMed)

Dentali F, Malato A, Ageno W, Imperatori A, Cajozzo M, Rotolo N, Douketis J, Siragusa S, Crowther M. Incidence of venous thromboembolism in patients undergoing thoracotomy for lung cancer. J Thorac Cardiovasc Surg. 2008 Mar;135(3):705-6. doi: 10.1016/j.jtcvs.2007.10.036. No abstract available.

Reference Type: BACKGROUND

PMID: 18329505 (View on PubMed)

Ziomek S, Read RC, Tobler HG, Harrell JE Jr, Gocio JC, Fink LM, Ranval TJ, Ferris EJ, Harshfield DL, McFarland DR, et al. Thromboembolism in patients undergoing thoracotomy. Ann Thorac Surg. 1993 Aug;56(2):223-6; discussion 227. doi: 10.1016/0003-4975(93)91151-c.

Reference Type: BACKGROUND

PMID: 8347002 (View on PubMed)

Saarinen J, Kallio T, Sisto T, Tarkka M. Incidence of deep venous thrombosis after thoracotomy. Vasa. 2001 Nov;30(4):259-61. doi: 10.1024/0301-1526.30.4.259.

Reference Type: BACKGROUND

PMID: 11771209 (View on PubMed)

Cade JF, Clegg EA, Westlake GW. Prophylaxis of venous thrombosis after major thoracic surgery. Aust N Z J Surg. 1983 Aug;53(4):301-4. doi: 10.1111/j.1445-2197.1983.tb02451.x.

Reference Type: BACKGROUND

PMID: 6577843 (View on PubMed)

Azorin JF, Regnard JF, Dahan M, Pansart M. [Efficacy and tolerability of fraxiparine in the prevention of thromboembolic complications in oncologic thoracic surgery]. Ann Cardiol Angeiol (Paris). 1997 May-Jun;46(5-6):341-7. French.

Reference Type: BACKGROUND

PMID: 9295896 (View on PubMed)

Hull RD, Pineo GF, Stein PD, Mah AF, MacIsaac SM, Dahl OE, Butcher M, Brant RF, Ghali WA, Bergqvist D, Raskob GE. Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med. 2001 Nov 20;135(10):858-69. doi: 10.7326/0003-4819-135-10-200111200-00006.

Reference Type: BACKGROUND

PMID: 11712876 (View on PubMed)

Bergqvist D, Benoni G, Bjorgell O, Fredin H, Hedlundh U, Nicolas S, Nilsson P, Nylander G. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996 Sep 5;335(10):696-700. doi: 10.1056/NEJM199609053351002.

Reference Type: BACKGROUND

PMID: 8703168 (View on PubMed)

Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet. 1996 Jul 27;348(9022):224-8. doi: 10.1016/s0140-6736(96)01453-5.

Reference Type: BACKGROUND

PMID: 8684199 (View on PubMed)

Hull RD, Pineo GF, Francis C, Bergqvist D, Fellenius C, Soderberg K, Holmqvist A, Mant M, Dear R, Baylis B, Mah A, Brant R. Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators. Arch Intern Med. 2000 Jul 24;160(14):2208-15. doi: 10.1001/archinte.160.14.2208.

Reference Type: BACKGROUND

PMID: 10904465 (View on PubMed)

Lassen MR, Borris LC, Anderson BS, Jensen HP, Skejo Bro HP, Andersen G, Petersen AO, Siem P, Horlyck E, Jensen BV, Thomsen PB, Hansen BR, Erin-Madsen J, Moller JC, Rotwitt L, Christensen F, Nielsen JB, Jorgensen PS, Paaske B, Torholm C, Hvidt P, Jensen NK, Nielsen AB, Appelquist E, Tjalve E, et al. Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study. Thromb Res. 1998 Mar 15;89(6):281-7. doi: 10.1016/s0049-3848(98)00018-8.

Reference Type: BACKGROUND

PMID: 9669750 (View on PubMed)

White RH, Romano PS, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med. 1998 Jul 27;158(14):1525-31. doi: 10.1001/archinte.158.14.1525.

Reference Type: BACKGROUND

PMID: 9679793 (View on PubMed)

Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005 Jun;6(6):401-10. doi: 10.1016/S1470-2045(05)70207-2.

Reference Type: BACKGROUND

PMID: 15925818 (View on PubMed)

White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost. 2003 Sep;90(3):446-55. doi: 10.1160/TH03-03-0152.

Reference Type: BACKGROUND

PMID: 12958614 (View on PubMed)

Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E, Moia M, Parazzini F, Rossi R, Sonaglia F, Valarani B, Bianchini C, Gussoni G. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg. 2006 Jan;243(1):89-95. doi: 10.1097/01.sla.0000193959.44677.48.

Reference Type: BACKGROUND

PMID: 16371741 (View on PubMed)

Bottaro FJ, Elizondo MC, Doti C, Bruetman JE, Perez Moreno PD, Bullorsky EO, Ceresetto JM. Efficacy of extended thrombo-prophylaxis in major abdominal surgery: what does the evidence show? A meta-analysis. Thromb Haemost. 2008 Jun;99(6):1104-11. doi: 10.1160/TH07-12-0759.

Reference Type: BACKGROUND

PMID: 18521515 (View on PubMed)

Kakkar VV, Balibrea JL, Martinez-Gonzalez J, Prandoni P; CANBESURE Study Group. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. J Thromb Haemost. 2010 Jun;8(6):1223-9. doi: 10.1111/j.1538-7836.2010.03892.x. Epub 2010 Apr 30.

Reference Type: BACKGROUND

PMID: 20456751 (View on PubMed)

Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e351S-e418S. doi: 10.1378/chest.11-2299.

Reference Type: BACKGROUND

PMID: 22315267 (View on PubMed)

Hurwitz LM, Yoshizumi TT, Goodman PC, Nelson RC, Toncheva G, Nguyen GB, Lowry C, Anderson-Evans C. Radiation dose savings for adult pulmonary embolus 64-MDCT using bismuth breast shields, lower peak kilovoltage, and automatic tube current modulation. AJR Am J Roentgenol. 2009 Jan;192(1):244-53. doi: 10.2214/AJR.08.1066.

Reference Type: BACKGROUND

PMID: 19098206 (View on PubMed)

Sodickson A, Baeyens PF, Andriole KP, Prevedello LM, Nawfel RD, Hanson R, Khorasani R. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology. 2009 Apr;251(1):175-84. doi: 10.1148/radiol.2511081296.

Reference Type: BACKGROUND

PMID: 19332852 (View on PubMed)

Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. National Institute for Health and Clinical Excellence (NICE). 2010

Reference Type: BACKGROUND

Other Identifiers

13-368

Identifier Type: OTHER

Identifier Source: secondary_id

SJHH_VTEincidence

Identifier Type: -

Identifier Source: org_study_id