A Different Approach to Preventing Thrombosis

NCT02774265 | Completed Phase 3 Results DMC

• 1 other identifier: HP-00065750
• Study Type: interventional
• Target: 329
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to perform a pragmatic randomized controlled trial to compare the use of low molecular weight heparin (LMWH, lovenox, enoxaparin) versus acetylsalicylic acid (ASA) for venous thromboembolism (VTE) prophylaxis in patients with high-risk lower extremity fractures.

Conditions

Venous Thromboembolism; Pulmonary Embolism

Keywords

Fracture; Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Bleeding Events as Assessed by the Need for Blood Transfusions and Procedures for Bleeding Complications After Initiation of the Study Medication.

  Includes a greater than 2g/dL drop in hemoglobin, blood transfusion, hematoma evacuation, re-operation for a deep surgical site infection or minor procedure for bleeding and GI bleed

  90 days

Secondary Outcomes (2)

• Number of Participants With Deep Venous Thromboembolism

  90 days

• Number of Participants With Pulmonary Embolism Events

  90 days

Study Arms (2)

VTE prophylaxis with Enoxaparin 30mg BID

ACTIVE COMPARATOR

The group receiving VTE prophylaxis with enoxaparin 30mg subcutaneous BID.

Drug: VTE prophylaxis with Enoxaparin 30mg BID

VTE prophylaxis with Aspirin 81mg BID

ACTIVE COMPARATOR

The group receiving VTE prophylaxis with ASA 81mg PO BID

Drug: VTE prophylaxis with Aspirin 81mg BID

Interventions

VTE prophylaxis with Enoxaparin 30mg BID DRUG

Patients will receive Enoxaparin 30mg BID for DVT prophylaxis and will be followed to determine the efficacy, safety and cost when used for VTE prophylaxis in high-risk orthopedic traumas administered for the length of time indicated by standard of care based on the injury.

Also known as: Lovenox, Low Molecular Weight Heparin (LMWH)

VTE prophylaxis with Enoxaparin 30mg BID

VTE prophylaxis with Aspirin 81mg BID DRUG

Patients will receive Aspirin 81mg BID for DVT prophylaxis and will be followed to determine the efficacy, safety and cost when used for VTE prophylaxis in high-risk orthopedic traumas administered for the length of time indicated by standard of care based on the injury.

Also known as: ASA (Acetylsalicylic Acid)

VTE prophylaxis with Aspirin 81mg BID

Eligibility Criteria

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

You may qualify if:

• All patients treated at a level-1 trauma center with any one or more of the following injuries: Pelvis fracture (operative or non-operative), Acetabulum fracture (operative or non-operative), or any operative extremity fracture (proximal to metatarsals/carpals)
• Age greater than or equal to 18 years old

You may not qualify if:

• Patients receiving pre-existing confounding prophylaxis or therapeutic anticoagulation (not to include anti-platelet agents) prior to admission or those receiving greater than one dose of LMWH since injury
• Patients with pre-existing coagulopathy
• Patients with a previous history of VTE within the last 6 months
• Patients who are pregnant
• Patients with CNS or spinal cord injury with potential need for further neurosurgical intervention precluding anticoagulation with aspirin
• Patients with active bleeding precluding the use of anticoagulation
• Impaired creatinine clearance \<30ml/min at the time of randomization
• History of Heparin Induced Thrombocytopenia or ASA or NSAID allergy
• Prisoners
• Non-english speaking patients
• Patients who have an indication for therapeutic anticoagulation
• Patients who would not normally receive VTE prophylaxis for their injury

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (40)

• Cohen AT, Imfeld S, Markham J, Granziera S. The use of aspirin for primary and secondary prevention in venous thromboembolism and other cardiovascular disorders. Thromb Res. 2015 Feb;135(2):217-25. doi: 10.1016/j.thromres.2014.11.036. Epub 2014 Dec 13.

  PMID: 25541030 BACKGROUND

• Selby R, Geerts WH, Kreder HJ, Crowther MA, Kaus L, Sealey F; D-KAF (Dalteparin in Knee-to-Ankle Fracture) Investigators. A double-blind, randomized controlled trial of the prevention of clinically important venous thromboembolism after isolated lower leg fractures. J Orthop Trauma. 2015 May;29(5):224-30. doi: 10.1097/BOT.0000000000000250.

  PMID: 25900749 BACKGROUND

• Scolaro JA, Taylor RM, Wigner NA. Venous thromboembolism in orthopaedic trauma. J Am Acad Orthop Surg. 2015 Jan;23(1):1-6. doi: 10.5435/JAAOS-23-01-1.

  PMID: 25538125 BACKGROUND

• Gritsiouk Y, Hegsted DA, Schlesinger P, Gardiner SK, Gubler KD. A retrospective analysis of the effectiveness of low molecular weight heparin for venous thromboembolism prophylaxis in trauma patients. Am J Surg. 2014 May;207(5):648-51; discussion 651-2. doi: 10.1016/j.amjsurg.2013.12.010. Epub 2014 Jan 30.

  PMID: 24560359 BACKGROUND

• Schousboe JT, Brown GA. Cost-effectiveness of low-molecular-weight heparin compared with aspirin for prophylaxis against venous thromboembolism after total joint arthroplasty. J Bone Joint Surg Am. 2013 Jul 17;95(14):1256-64. doi: 10.2106/JBJS.L.00400.

  PMID: 23864173 BACKGROUND

• Lieberman JR, Pensak MJ. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am. 2013 Oct 2;95(19):1801-11. doi: 10.2106/JBJS.L.01328.

  PMID: 24088973 BACKGROUND

• Mortazavi SM, Hansen P, Zmistowski B, Kane PW, Restrepo C, Parvizi J. Hematoma following primary total hip arthroplasty: a grave complication. J Arthroplasty. 2013 Mar;28(3):498-503. doi: 10.1016/j.arth.2012.07.033. Epub 2012 Oct 31.

  PMID: 23122656 BACKGROUND

• Brakenridge SC, Henley SS, Kashner TM, Golden RM, Paik DH, Phelan HA, Cohen MJ, Sperry JL, Moore EE, Minei JP, Maier RV, Cuschieri J; Inflammation and the Host Response to Injury Investigators. Comparing clinical predictors of deep venous thrombosis versus pulmonary embolus after severe injury: a new paradigm for posttraumatic venous thromboembolism? J Trauma Acute Care Surg. 2013 May;74(5):1231-7; discussion 1237-8. doi: 10.1097/TA.0b013e31828cc9a0.

  PMID: 23609272 BACKGROUND

• Sagi HC, Dziadosz D, Mir H, Virani N, Olson C. Obesity, leukocytosis, embolization, and injury severity increase the risk for deep postoperative wound infection after pelvic and acetabular surgery. J Orthop Trauma. 2013 Jan;27(1):6-10. doi: 10.1097/BOT.0b013e31825cf382.

  PMID: 23263468 BACKGROUND

• Raphael IJ, Tischler EH, Huang R, Rothman RH, Hozack WJ, Parvizi J. Aspirin: an alternative for pulmonary embolism prophylaxis after arthroplasty? Clin Orthop Relat Res. 2014 Feb;472(2):482-8. doi: 10.1007/s11999-013-3135-z.

  PMID: 23817755 BACKGROUND

• Stewart DW, Freshour JE. Aspirin for the prophylaxis of venous thromboembolic events in orthopedic surgery patients: a comparison of the AAOS and ACCP guidelines with review of the evidence. Ann Pharmacother. 2013 Jan;47(1):63-74. doi: 10.1345/aph.1R331. Epub 2013 Jan 16.

  PMID: 23324504 BACKGROUND

• Anderson DR, Dunbar MJ, Bohm ER, Belzile E, Kahn SR, Zukor D, Fisher W, Gofton W, Gross P, Pelet S, Crowther M, MacDonald S, Kim P, Pleasance S, Davis N, Andreou P, Wells P, Kovacs M, Rodger MA, Ramsay T, Carrier M, Vendittoli PA. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med. 2013 Jun 4;158(11):800-6. doi: 10.7326/0003-4819-158-11-201306040-00004.

  PMID: 23732713 BACKGROUND

• Cossetto DJ, Goudar A, Parkinson K. Safety of peri-operative low-dose aspirin as a part of multimodal venous thromboembolic prophylaxis for total knee and hip arthroplasty. J Orthop Surg (Hong Kong). 2012 Dec;20(3):341-3. doi: 10.1177/230949901202000315.

  PMID: 23255642 BACKGROUND

• Vulcano E, Gesell M, Esposito A, Ma Y, Memtsoudis SG, Gonzalez Della Valle A. Aspirin for elective hip and knee arthroplasty: a multimodal thromboprophylaxis protocol. Int Orthop. 2012 Oct;36(10):1995-2002. doi: 10.1007/s00264-012-1588-4. Epub 2012 Jun 12.

  PMID: 22684546 BACKGROUND

• Mont MA, Jacobs JJ. AAOS clinical practice guideline: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg. 2011 Dec;19(12):777-8. doi: 10.5435/00124635-201112000-00008. No abstract available.

  PMID: 22134210 BACKGROUND

• Bozic KJ, Vail TP, Pekow PS, Maselli JH, Lindenauer PK, Auerbach AD. Does aspirin have a role in venous thromboembolism prophylaxis in total knee arthroplasty patients? J Arthroplasty. 2010 Oct;25(7):1053-60. doi: 10.1016/j.arth.2009.06.021. Epub 2009 Aug 12.

  PMID: 19679434 BACKGROUND

• Hill J, Treasure T; Guideline Development Group. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital: summary of the NICE guideline. Heart. 2010 Jun;96(11):879-82. doi: 10.1136/hrt.2010.198275. No abstract available.

  PMID: 20478866 BACKGROUND

• Slobogean GP, Lefaivre KA, Nicolaou S, O'Brien PJ. A systematic review of thromboprophylaxis for pelvic and acetabular fractures. J Orthop Trauma. 2009 May-Jun;23(5):379-84. doi: 10.1097/BOT.0b013e3181a5369c.

  PMID: 19390367 BACKGROUND

• Goel DP, Buckley R, deVries G, Abelseth G, Ni A, Gray R. Prophylaxis of deep-vein thrombosis in fractures below the knee: a prospective randomised controlled trial. J Bone Joint Surg Br. 2009 Mar;91(3):388-94. doi: 10.1302/0301-620X.91B3.20820.

  PMID: 19258618 BACKGROUND

• Novicoff WM, Brown TE, Cui Q, Mihalko WM, Slone HS, Saleh KJ. Mandated venous thromboembolism prophylaxis: possible adverse outcomes. J Arthroplasty. 2008 Sep;23(6 Suppl 1):15-9. doi: 10.1016/j.arth.2008.04.014. Epub 2008 Jun 13.

  PMID: 18555656 BACKGROUND

• Watson HG, Chee YL. Aspirin and other antiplatelet drugs in the prevention of venous thromboembolism. Blood Rev. 2008 Mar;22(2):107-16. doi: 10.1016/j.blre.2007.11.001. Epub 2008 Jan 15.

  PMID: 18226435 BACKGROUND

• Myers DD Jr, Wrobleski SK, Longo C, Bedard PW, Kaila N, Shaw GD, Londy FJ, Rohrer SE, Fex BA, Zajkowski PJ, Meier TR, Hawley AE, Farris DM, Ballard NE, Henke PK, Schaub RG, Wakefield TW. Resolution of venous thrombosis using a novel oral small-molecule inhibitor of P-selectin (PSI-697) without anticoagulation. Thromb Haemost. 2007 Mar;97(3):400-7.

  PMID: 17334507 BACKGROUND

• Slavik RS, Chan E, Gorman SK, de Lemos J, Chittock D, Simons RK, Wing PC, Ho SG. Dalteparin versus enoxaparin for venous thromboembolism prophylaxis in acute spinal cord injury and major orthopedic trauma patients: 'DETECT' trial. J Trauma. 2007 May;62(5):1075-81; discussion 1081. doi: 10.1097/TA.0b013e31804fa177.

  PMID: 17495705 BACKGROUND

• Burnett RS, Clohisy JC, Wright RW, McDonald DJ, Shively RA, Givens SA, Barrack RL. Failure of the American College of Chest Physicians-1A protocol for lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty. 2007 Apr;22(3):317-24. doi: 10.1016/j.arth.2007.01.007.

  PMID: 17400085 BACKGROUND

• Stannard JP, Lopez-Ben RR, Volgas DA, Anderson ER, Busbee M, Karr DK, McGwin GR Jr, Alonso JE. Prophylaxis against deep-vein thrombosis following trauma: a prospective, randomized comparison of mechanical and pharmacologic prophylaxis. J Bone Joint Surg Am. 2006 Feb;88(2):261-6. doi: 10.2106/JBJS.D.02932.

  PMID: 16452735 BACKGROUND

• Myers DD Jr, Rectenwald JE, Bedard PW, Kaila N, Shaw GD, Schaub RG, Farris DM, Hawley AE, Wrobleski SK, Henke PK, Wakefield TW. Decreased venous thrombosis with an oral inhibitor of P selectin. J Vasc Surg. 2005 Aug;42(2):329-36. doi: 10.1016/j.jvs.2005.04.045.

  PMID: 16102635 BACKGROUND

• Steele N, Dodenhoff RM, Ward AJ, Morse MH. Thromboprophylaxis in pelvic and acetabular trauma surgery. The role of early treatment with low-molecular-weight heparin. J Bone Joint Surg Br. 2005 Feb;87(2):209-12. doi: 10.1302/0301-620x.87b2.14447.

  PMID: 15736745 BACKGROUND

• Jorgensen PS, Warming T, Hansen K, Paltved C, Vibeke Berg H, Jensen R, Kirchhoff-Jensen R, Kjaer L, Kerbouche N, Leth-Espensen P, Narvestad E, Rasmussen SW, Sloth C, Torholm C, Wille-Jorgensen P. Low molecular weight heparin (Innohep) as thromboprophylaxis in outpatients with a plaster cast: a venografic controlled study. Thromb Res. 2002 Mar 15;105(6):477-80. doi: 10.1016/s0049-3848(02)00059-2.

  PMID: 12091045 BACKGROUND

• Rogers FB, Cipolle MD, Velmahos G, Rozycki G, Luchette FA. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: the EAST practice management guidelines work group. J Trauma. 2002 Jul;53(1):142-64. doi: 10.1097/00005373-200207000-00032. No abstract available.

  PMID: 12131409 BACKGROUND

• Lassen MR, Borris LC, Nakov RL. Use of the low-molecular-weight heparin reviparin to prevent deep-vein thrombosis after leg injury requiring immobilization. N Engl J Med. 2002 Sep 5;347(10):726-30. doi: 10.1056/NEJMoa011327.

  PMID: 12213943 BACKGROUND

• Brookenthal KR, Freedman KB, Lotke PA, Fitzgerald RH, Lonner JH. A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty. J Arthroplasty. 2001 Apr;16(3):293-300. doi: 10.1054/arth.2001.21499.

  PMID: 11307125 BACKGROUND

• Hak DJ. Prevention of venous thromboembolism in trauma and long bone fractures. Curr Opin Pulm Med. 2001 Sep;7(5):338-43. doi: 10.1097/00063198-200109000-00015.

  PMID: 11584186 BACKGROUND

• Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000 Apr 15;355(9212):1295-302.

  PMID: 10776741 BACKGROUND

• Greenfield LJ, Proctor MC, Rodriguez JL, Luchette FA, Cipolle MD, Cho J. Posttrauma thromboembolism prophylaxis. J Trauma. 1997 Jan;42(1):100-3. doi: 10.1097/00005373-199701000-00017.

  PMID: 9003265 BACKGROUND

• Lotke PA, Palevsky H, Keenan AM, Meranze S, Steinberg ME, Ecker ML, Kelley MA. Aspirin and warfarin for thromboembolic disease after total joint arthroplasty. Clin Orthop Relat Res. 1996 Mar;(324):251-8. doi: 10.1097/00003086-199603000-00031.

  PMID: 8595765 BACKGROUND

• Collaborative overview of randomised trials of antiplatelet therapy--III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration. BMJ. 1994 Jan 22;308(6923):235-46.

  PMID: 8054013 BACKGROUND

• Schumacher WA, Heran CL. Effect of thromboxane receptor antagonists on venous thrombosis in rats. J Pharmacol Exp Ther. 1989 Mar;248(3):1109-15.

  PMID: 2522985 BACKGROUND

• Vesterqvist O, Green K, Johnsson H. Thromboxane and prostacyclin formation in patients with deep vein thrombosis. Thromb Res. 1987 Feb 15;45(4):393-402. doi: 10.1016/0049-3848(87)90228-3.

  PMID: 3554598 BACKGROUND

• McKenna R, Galante J, Bachmann F, Wallace DL, Kaushal PS, Meredith P. Prevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression. Br Med J. 1980 Feb 23;280(6213):514-7. doi: 10.1136/bmj.280.6213.514.

  PMID: 6989432 BACKGROUND

• Harris WH, Salzman EW, Athanasoulis CA, Waltman AC, DeSanctis RW. Aspirin prophylaxis of venous thromboembolism after total hip replacement. N Engl J Med. 1977 Dec 8;297(23):1246-9. doi: 10.1056/NEJM197712082972302.

  PMID: 335247 BACKGROUND

MeSH Terms

Conditions

Venous Thromboembolism; Pulmonary Embolism; Fractures, Bone

Interventions

Enoxaparin; BID protein, human; Heparin, Low-Molecular-Weight; Aspirin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Bryce Haac
• Organization: University of Maryland Medical Center

bhaac@som.umaryland.edu

410-328-3495

Study Officials

• Deborah Stein, MD, MPH

  R. Adams Cowley Shock Trauma Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery, Chief of Trauma

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 17, 2016
• Study Start: January 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: September 1, 2017
• Last Updated: January 5, 2022
• Results First Posted: July 24, 2018

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)