Skip to main content

Advertisement

SpringerLink
Log in

Are large fracture trials really possible? What we have learned from the randomized controlled damage control study?

  • Original Article
  • Published:
European Journal of Trauma and Emergency Surgery Aims and scope Submit manuscript

Abstract

Purpose

Although they are considered the ‘gold standard’ of evidence-based medicine, randomized controlled trials are still a rarity in orthopedic surgery. In the management of patients with multiple trauma, there is a current trend toward ‘damage control orthopedics’, but to date, there is no proof of the superiority of this concept in terms of evidence-based medicine. The purpose of this article is to present unexpected difficulties we encountered in successfully completing our randomized controlled trial and to discuss the problematic differences between theoretically planning a trial and real-life practical experience of implementing the plan, with attention to published strategies.

Methods

The multicenter randomized controlled trial on risk adapted damage control orthopedic surgery of femur shaft fractures in multiple trauma patients (DCO study) was designed to determine whether ‘risk adapted damage control orthopedics’ of femoral shaft fractures is advantageous when treating multiple trauma patients. We compared our methods of study planning and realization point by point with published methods for conducting such trials.

Results

The study was methodically planned. We met the most prerequisites for successfully completing a large fracture trial, but experienced unexpected difficulties. After 2.5 years, the Deutsche Forschungsgemeinschaft suspended the financing because of low recruitment. The reasons were multifactorial.

Conclusions

We believe it is much more difficult to perform a large fracture trial in reality than to plan it in theory. Even the theoretically best designed trial can prove unsuccessful in its implementation. The question remains: are large fracture trials even possible? Hopefully YES!

Trial registration

Current Controlled Trials ISRCTN10321620. Date assigned: 09/02/2007.

Level of evidence

Level I.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Trauma Registry of the German Trauma Society: annual reports. 2017. http://www.traumaregister.de.

  2. Morshed S, Bhandari M. Clinical trial design in fracture-healing research: Meeting the challenge. J Bone Jt Surg Am. 2008;90(Suppl 1):55–61.

    Article  Google Scholar 

  3. Bono CM, Tornetta P. Common errors in the desgin of orthopaedic studies. Injury. 2006;37:355–60.

    Article  Google Scholar 

  4. Bhandari M, Pape HC, Giannoudis PV. Issues in the planning and conduct of randomised trials. Injury. 2006;37:349–54.

    Article  Google Scholar 

  5. Simunovic N, Devereaux PJ, Bhandari M. Design considerations for randomised trials in orthopaedic fracture surgery. Injury. 2008;39:696–704.

    Article  Google Scholar 

  6. Mejaddam AY, Velmahos GC. Randomized controlled trials affecting polytrauma care. Eur J Trauma Emerg Surg. 2012;38:211–21.

    Article  CAS  Google Scholar 

  7. Hauser CJ, Boffard K, Dutton R, et al. Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage. J Trauma. 2010;69:489–500.

    Article  CAS  Google Scholar 

  8. Bartl C, Stengel D, Bruckner T, et al. Open reduction and internal fixation versus casting for highly comminuted and intra-articular fractures of the distal radius (ORCHID): protocol for a randomized clinical multi-center trial. Trials. 2011;22;12:84.

    Article  Google Scholar 

  9. Rixen D, Steinhausen E, Sauerland S, et al. Protocol for a randomized controlled trial on risk adapted damage control orthopedic surgery of femur shaft fractures in multiple trauma patients. Trials. 2009;19;10:72.

    Article  Google Scholar 

  10. Dutton R, Hauser C, Boffard K, et al. Scientific and logistical challenges in designing the CONTROL trial: recombinant factor VII in severe trauma patients with refractory bleeding. Clin Trials. 2009;6:467–79.

    Article  Google Scholar 

  11. Rixen D, Grass G, Sauerland S, et al. Evaluation of criteria for temporary external fixation in risk-adapted damage control orthopedic surgery of femur shaft fractures in multiple trauma patients: “evidence-based medicine” versus “reality” in the trauma registry of the German Trauma Society. J Trauma. 2005;59:1375–94.

    Article  Google Scholar 

  12. Rixen D, Steinhausen E, Sauerland S, et al. Randomized, controlled, two-arm, interventional, multicenter study on risk-adapted damage control orthopedic surgery of femur shaft fractures in multiple-trauma patients. Trials. 2016;25:17:47.

    Article  Google Scholar 

  13. Csimma C, Swiontkowski MF. Large clinical trials in musculoskeletal trauma: Are they possible? J Bone Jt Surg. 2005;87:218–22.

    Google Scholar 

  14. Chan S, Bhandari M. The quality of reporting of orthopaedic randomized trials with use of a checklist for nonpharmacological therapies. J Bone Jt Surg Am. 2007;89:1970–8.

    Google Scholar 

  15. Jeray KJ, Tanner S, Schemitsch EH, et al. Are large fracture trials possible? J Orthop Trauma. 2010;24:S87–92.

    Article  Google Scholar 

  16. MacKenzie EJ, Bosse MJ, Pollak AN, et al. Long-term persistence of disability following severe lower-limb trauma. Results of a seven-year follow-up. J Bone Jt Surg Am. 2005;87:1801–9.

    Google Scholar 

  17. Bhandari M, Guyatt G, Investigators, et al. Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures: Study to prospectively evaluate reamed intramedullary nails in patients with tibial fractures. J Bone Jt Surg Am. 2008;90:2567–78.

    Article  Google Scholar 

  18. Helfet DL, Suk M, Hanson B. A critical appraisal of the SPRINT trial. Orthop Clin N Am. 2010;41:241–7.

    Article  Google Scholar 

  19. Govender S, Csimma C, Genant HK, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Jt Surg Am. 2002;84:2123–34.

    Article  Google Scholar 

  20. Rixen D, Raum M, Bouillon B, et al. Predicting the outcome in severe injuries: an analysis of 2069 patients from the trauma register of the German Society of Traumatology (DGU). Unfallchirurg. 2001;104:230–9.

    Article  CAS  Google Scholar 

  21. Dunham CM, Bosse MJ, Clancy TV, et al. Practice management guidelines for the optimal timing of long-bone fracture stabilization in polytrauma patients: the EAST Practice Management Work Group. J Trauma. 2001; 50:958–67.

  22. Pape HC, Rixen D, Morley J, et al. Impact of the method of initial stabilization for femoral shaft fractures in patients with multiple injuries at risk for complications (borderline patients). Ann Surg. 2007;246:491–501.

    Article  Google Scholar 

  23. Ferreira FL, Bota DP, Bross A, et al. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286:1754–8.

    Article  CAS  Google Scholar 

  24. Morrison CA, Horwitz IB, Carrick MM. Ethical and legal issues in emergency research: barriers to conducting prospective randomized trials in an emergency setting. J Surg Res. 2009;157(1):115–22.

    Article  Google Scholar 

  25. Rice TW, Morris S, Tortella BJ, et al. Deviations from evidence-based clinical management guidelines increase mortality in critically injured trauma patients. Crit Care Med. 2012;40(3):778–86.

    Article  Google Scholar 

  26. Bednarska E, Bryant D, Devereaux PJ, et al. Orthopaedic surgeons prefer to participate in expertise-based randomized trials. Clin Orthop Relat Res. 2008;466:1734–44.

    Article  Google Scholar 

  27. Soucacos PN, Johnson EO, Babis G. Randomised controlled trials in orthopaedic surgery and traumatology: Overview of parameters and pitfalls. Injury. 2008;39:636–42.

    Article  Google Scholar 

  28. Bhandari M, Richards RR, Sprague S, et al. The quality of reporting of randomized trials in the Journal of Bone and Joint Surgery from 1988 through 2000. J Bone Jt Surg Am. 2002; 84A:388–96.

    Article  Google Scholar 

  29. Huber-Wagner S, Lefering R, Qvick LM, et al. Effect of whole-body CT during trauma resuscitation on survival: a retrospective, multicentre study. Lancet. 2009;373:1455–61.

    Article  Google Scholar 

  30. Brinck T, Handolin L, Paffrath T, et al. Trauma registry comparison: six-year results in trauma care in Southern Finland and Germany. Eur J Trauma Emerg Surg. 2015;41:509–16.

    Article  CAS  Google Scholar 

  31. Timm A, Maegele M, Lefering R, et al. Pre-hospital rescue times and actions in severe trauma. A comparison between two trauma systems: Germany and the Netherlands. Injury. 2014;45(Suppl 3):S43–52.

    Article  Google Scholar 

  32. Brinck T, Raj R, Skrifvars MB, et al. Unconscious trauma patients: outcome differences between Finland and Germany: lessons learned from trauma-registry comparisons. Eur J Trauma Emerg Surg. 2016;42:445–51.

    Article  Google Scholar 

  33. Thien TM, Chatziagorou G, Garellick G, et al. Periprosthetic femoral fracture within two years after total hip replacement: analysis of 437,629 operations in the nordic arthroplasty register association database. J Bone Jt Surg Am. 2014;1;96(19):e167.

    Article  Google Scholar 

  34. Cnudde PH, Kärrholm J, Rolfson O, et al. Cement-in-cement revision of the femoral stem: analysis of 1179 first-time revisions in the Swedish Hip Arthroplasty Register. Bone Jt J. 2017; 99-B(4 Supple B):27–32.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the members of the Study Steering Committee, the Data Safety Monitoring Board and the Ethics Committee for their supervision. We thank Dr. Melanie Affüpper-Fink (Institute for Research in Operative Medicine, University of Witten-Herdecke, Cologne, Germany), as well as the Coordinating Center for Clinical Studys Cologne (KKSK) for their help in performing the study.

Dr. G. Matthes1, PD Dr. H.J. Bail2, Dr. C. Grüber3, PD Dr. W. Zenker4, PD Dr. C. Burger5, Prof. Dr. D. Rixen6, Dr. E. Steinhauen6, Dr. G. Schiffer7, Prof. Dr. S. Flohe8, Dr. T. Lögters8, Prof. Dr. G. Täger9, Dr. B. Hußmann9, Prof. Dr. I. Marzi10, Dr. S. Wutzler10, Dr. A. Bonk11, Dr. M. Kremer11, Dr. L. Irlenbusch12, Prof. Dr. J.M. Rueger13, Prof. Dr. F. Hildebrand14, Dr. P. Mommsen14, Dr. O. Schoierer15, Dr. M. Burkhardt16, Dr. J. Scherer17, Prof. Dr. A. Seekamp18, Prof. Dr. C. Josten19, Dr. C. Wölfl20, Prof. Dr. C. Jürgens21, Dr. M. Zimmermann22, Prof. Dr. S. Ruchholtz23, Prof. Dr. W. Mutschler24, Dr. S. Huber-Wagner24, Dr. H. Trentzsch25, Dr. A. Ernstberger26, Prof. Dr. T. Mittlmeier27.

1Department of Trauma and Reconstructive Surgery, Unfallkrankenhaus Berlin (UKB), Berlin, Germany;2Center for Musculosceletal Surgery, Department of Trauma and Reconstructive Surgery, University of Berlin Charite Campus Virchow Clinic, Berlin, Germany;3Department of Trauma, Hand and Reconstructive Surgery, Helios Clinic Berlin-Buch, Berlin, Germany;4Department of Surgery, Trauma and Reconstructive Surgery Vivantes-Clinic Berlin, Berlin, Germany;5Department of Orthopedic and Trauma Surgery, University of Bonn, Bonn, Germany;6Department of Trauma Surgery, Orthopedics and Sporttraumatology, University of Witten-Herdecke at the Campus Cologne-Merheim, Cologne, Germany;7Department of Trauma, Hand and Reconstructive Surgery, University of Cologne, Cologne, Germany;8Department of Trauma and Hand Surgery, University of Düsseldorf, Düsseldorf, Germany;9Department of Trauma Surgery, University of Essen, Essen, Germany;10Department of Trauma, Hand and Reconstructive Surgery, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany;11Center for Trauma Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt, Frankfurt, Germany;12Department of Trauma Surgery University of Halle, Halle, Germany;13Department of Trauma, Hand and Reconstructive Surgery, University of Hamburg, Hamburg, Germany;14Department of Trauma Surgery Medical University of Hannover, Hannover, Germany;15Department of Trauma Surgery, Surgical University Hospital Heidelberg, Heidelberg, Germany;16Department of Trauma, Hand and Reconstructive Surgery University of Saarland (Homburg), Homburg, Germany;17Department of Trauma Surgery, Clinic Ingolstadt, Ingolstadt, Germany;18Department of Trauma Surgery, University Hospitals Schleswig-Holstein, Campus Kiel, Kiel, Germany;19Department of Trauma and Reconstructive Surgery, University of Leipzig, Leipzig, Germany;20Department of Trauma Surgery, Berufsgenossenschaftliche Unfallklinik Ludwigshafen, Ludwigshafen, Germany;21Department of Trauma Surgery, University Hospitals Schleswig-Holstein, Campus Lübeck, Lübeck, Germany;22Department of Trauma Surgery, St. Marien-Hospital Lünen, Lünen, Germany;23Department of Trauma, Reconstructive and Hand Surgery, University of Marburg/Gießen, Marburg, Germany;24Department of Trauma Surgery, University of Munich, Campus Innenstadt, Munich, Germany;25Department of Trauma Surgery, University of Munich, Campus Großhadern, Munich, Germany;26Department of Trauma Surgery, University of Regensburg, Regensburg, Germany;27Department of Trauma and Reconstructive Surgery, University of Rostock, Rostock, Germany

Author information

Authors and Affiliations

  1. Department of Orthopedic and Trauma Surgery, BG Klinikum Duisburg, Großenbaumer Allee 250, 47249, Duisburg, Germany

    Eva Steinhausen

  2. Faculty of Health, University of Witten/Herdecke, Witten, Germany

    Eva Steinhausen, Bertil Bouillon & Dieter Rixen

  3. Department of Trauma, Orthopaedic Surgery and Sports Traumatology, Cologne Merheim Medical Center, University of Witten/ Herdecke, Ostmerheimer Str. 200, 51109, Cologne, Germany

    Bertil Bouillon

Authors
  1. Eva Steinhausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bertil Bouillon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dieter Rixen
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Members of the damage control study group

  • G. Matthes
  • , H. J. Bail
  • , C. Grüber
  • , W. Zenker
  • , C. Burger
  • , D. Rixen
  • , E. Steinhauen
  • , G. Schiffer
  • , S. Flohe
  • , T. Lögters
  • , G. Täger
  • , B. Hußmann
  • , I. Marzi
  • , S. Wutzler
  • , A. Bonk
  • , M. Kremer
  • , L. Irlenbusch
  • , J. M. Rueger
  • , F. Hildebrand
  • , P. Mommsen
  • , O. Schoierer
  • , M. Burkhardt
  • , J. Scherer
  • , A. Seekamp
  • , C. Josten
  • , C. Wölfl
  • , C. Jürgens
  • , M. Zimmermann
  • , S. Ruchholtz
  • , S. Mutschler
  • , S Huber-Wagner
  • , H. Trentzsch
  • , A. Ernstberger
  •  & T. Mittlmeier

Contributions

ES: drafted the manuscript, was the study manager and coordinated multicenter management. BB: clinical scientific advisor and conceived and designed the study. DR: principal coordinating investigator, conceived and designed the study, and drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Eva Steinhausen.

Ethics declarations

Funding

The Damage Control Study was funded by the Deutsche Forschungsgemeinschaft (grant number: RI 929/3-1).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 109 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Steinhausen, E., Bouillon, B., Rixen, D. et al. Are large fracture trials really possible? What we have learned from the randomized controlled damage control study?. Eur J Trauma Emerg Surg 44, 917–925 (2018). https://doi.org/10.1007/s00068-017-0891-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00068-017-0891-6

Keywords

Search

Navigation