Landmark trials

1. 2001
   SpineSpine

   Fritzell

   Lumbar fusion vs non-surgical care for chronic low back pain?

   Finding

   Fusion modestly reduced pain and disability at two years, though the non-operative comparator was weak.

2. 2002
   TraumaNEJM

   LEAP

   Limb salvage vs amputation after severe lower extremity trauma?

   Finding

   Two-year function was equivalent either way, and injury severity scores could not predict which limbs to salvage.

3. 2002
   SportsNEJM

   Moseley

   Arthroscopic debridement or lavage vs placebo surgery for knee osteoarthritis?

   Finding

   Arthroscopy was no better than sham at any point over two years, ending its routine use for osteoarthritis.

4. 2006
   SpineJAMA/NEJM

   SPORT

   Surgery vs non-operative care for disc herniation, spinal stenosis, and degenerative spondylolisthesis?

   Finding

   Heavy crossover blurred the intention-to-treat result; as-treated analyses favoured surgery, most clearly for stenosis and spondylolisthesis.

5. 2007
   SpineNEJM

   Peul

   Early surgery vs prolonged conservative care for severe sciatica of 6–12 weeks?

   Finding

   Early surgery relieved leg pain faster, but outcomes were equivalent by one year; waiting cost time, not outcome.

6. 2007
   TraumaJBJSCanadian-led

   COTS

   Plate fixation vs sling for completely displaced midshaft clavicle fractures?

   Finding

   Plating reduced nonunion and symptomatic malunion, though later trials tempered how much function that actually buys.

7. 2008
   TraumaJBJSCanadian-led

   SPRINT

   Reamed vs unreamed intramedullary nailing for tibial shaft fractures?

   Finding

   Reamed nailing reduced reoperations in closed fractures; no advantage in open fractures.

8. 2008
   SportsNEJMCanadian-led

   Kirkley

   Arthroscopic lavage and debridement plus optimised physical and medical therapy vs the therapy alone for knee osteoarthritis?

   Finding

   Arthroscopy added nothing to optimised non-operative care at two years — the active-comparator complement to Moseley that ended arthroscopy for knee OA.

9. 2009
   SpineNEJM

   Vertebroplasty sham trials

   Vertebroplasty vs a sham procedure for painful osteoporotic vertebral compression fractures?

   Finding

   Two simultaneous blinded trials found no benefit over sham out to six months; patient selection remains contested.

10. 2010
    TraumaLancet

    CRASH-2

    Tranexamic acid vs placebo in bleeding trauma patients?

    Finding

    TXA cut all-cause mortality without excess thrombosis, with the benefit concentrated within three hours of injury.

11. 2010
    SportsNEJM

    KANON

    Early ACL reconstruction plus rehabilitation vs rehabilitation with optional delayed reconstruction?

    Finding

    Outcomes matched at 2 and 5 years; over half the reconstructions could have been avoided.

12. 2010
    Foot & ankleJBJSCanadian-led

    Willits

    Operative vs non-operative treatment of acute Achilles rupture with accelerated functional rehabilitation?

    Finding

    With early functional rehab, non-operative care matched surgery and rerupture rates were far closer than historically taught.

13. 2011
    TraumaNEJM

    FOCUS

    Liberal (10 g/dL) vs restrictive (8 g/dL or symptoms) transfusion threshold after hip fracture surgery?

    Finding

    The restrictive threshold matched liberal transfusion for death and walking ability at 60 days, and most restrictive-arm patients avoided transfusion entirely.

14. 2013
    SportsNEJM

    FIDELITY

    Arthroscopic partial meniscectomy vs sham surgery for degenerative meniscal tears?

    Finding

    Meniscectomy was no better than sham surgery, a landmark for surgical placebo effects.

15. 2013
    SportsNEJM

    METEOR

    Surgery vs physiotherapy for meniscal tear with knee osteoarthritis?

    Finding

    No significant functional difference at 6–12 months, though many PT patients crossed over.

16. 2013
    ArthroplastyAnn Intern MedCanadian-led

    EPCAT I

    After ~10 days of dalteparin following THA, extend prophylaxis with aspirin or continued dalteparin?

    Finding

    Aspirin was non-inferior for symptomatic VTE, legitimising aspirin as extended prophylaxis — though enrolment stopped short of the planned 1,100.

17. 2014
    Hand & wristBMJ

    DRAFFT

    K-wires vs volar locking plates for dorsally displaced distal radius fractures?

    Finding

    No difference in patient-reported wrist function at 12 months; wires were cheaper.

18. 2015
    Shoulder & elbowJAMA

    PROFHER

    Surgical vs nonsurgical treatment for displaced proximal humerus fractures?

    Finding

    No difference in patient-reported outcomes over two years.

19. 2015
    TraumaNEJMCanadian-led

    FLOW

    Irrigation pressure and soap vs saline for open fracture wounds?

    Finding

    Very low pressure was acceptable; soap led to more reoperations than saline.

20. 2015
    ArthroplastyNEJM

    Skou

    Total knee replacement plus 12 weeks of non-surgical treatment vs the non-surgical treatment alone?

    Finding

    The first RCT of TKR itself: greater improvement with surgery, but far more serious adverse events, and many non-surgical patients never needed the operation.

21. 2016
    SpineNEJM

    Försth

    Decompression plus fusion vs decompression alone for lumbar stenosis, with or without degenerative spondylolisthesis?

    Finding

    Fusion added blood loss and operating time but no clinical benefit at 2 or 5 years.

22. 2016
    SpineNEJM

    SLIP

    Laminectomy plus fusion vs laminectomy alone for grade I degenerative spondylolisthesis?

    Finding

    Published beside Försth with the opposite conclusion: fusion modestly improved SF-36 physical scores and markedly reduced reoperation.

23. 2017
    TraumaLancetCanadian-led

    FAITH

    Sliding hip screw vs cancellous screws for femoral neck fractures?

    Finding

    No overall difference in reoperation at 24 months between fixation strategies.

24. 2018
    Shoulder & elbowLancet

    CSAW

    Arthroscopic subacromial decompression vs placebo arthroscopy for shoulder impingement?

    Finding

    Decompression offered no meaningful benefit over placebo surgery.

25. 2018
    TraumaJAMA

    WOLLF

    Negative pressure wound therapy vs standard dressings for severe open lower limb fractures?

    Finding

    No difference in disability at 12 months.

26. 2018
    ArthroplastyNEJMCanadian-led

    EPCAT II

    After 5 days of rivaroxaban following hip or knee arthroplasty, extend prophylaxis with aspirin or continued rivaroxaban?

    Finding

    Aspirin was non-inferior for VTE at 90 days, making the short-DOAC-then-aspirin switch mainstream — though everyone got rivaroxaban first.

27. 2019
    InfectionNEJM

    OVIVA

    Oral vs intravenous antibiotics for the first 6 weeks of treating bone, joint, or metalware-associated infection?

    Finding

    Oral therapy was non-inferior for treatment failure at one year, overturning a parenteral-only standard traceable to 1970.

28. 2019
    ArthroplastyNEJMCanadian-led

    HEALTH

    Total hip arthroplasty vs hemiarthroplasty for displaced femoral neck fractures?

    Finding

    No significant difference in secondary procedures at 24 months; modest functional gains with THA.

29. 2019
    ArthroplastyLancet

    TOPKAT

    Total vs partial knee replacement for isolated medial compartment osteoarthritis?

    Finding

    Both were effective at 5 years; partial replacement was cost-effective with similar outcomes.

30. 2020
    SpineNEJMCanadian-led

    Bailey

    Microdiscectomy vs 6 months of standardised non-operative care for sciatica already persisting 4–12 months?

    Finding

    Once symptoms were established beyond a few months, surgery genuinely outperformed continued conservative care — the chronic counterpart to Peul.

31. 2020
    TraumaLancetCanadian-led

    HIP ATTACK

    Accelerated surgery (within ~6 h) vs standard care for hip fracture?

    Finding

    Accelerated surgery did not reduce mortality or major complications versus standard timing.

32. 2020
    Shoulder & elbowLancet

    UK FROST

    Capsular release vs manipulation under anaesthesia vs structured physiotherapy for frozen shoulder?

    Finding

    No option was clearly superior; manipulation was the most cost-effective.

33. 2020
    Foot & ankleLancet

    UKSTAR

    Plaster cast vs functional brace for non-operatively treated Achilles rupture?

    Finding

    Early weight-bearing in a functional brace matched casting at nine months and was safe.

34. 2020
    Hand & wristPlast Reconstr Surg

    WRIST

    Volar plate vs external fixation vs pinning vs casting for distal radius fractures in adults 60 and over?

    Finding

    The plate recovered faster early but all arms converged by 12 months; cast malunion did not translate into worse function.

35. 2021
    Hand & wristJAMA Surgery

    CROSSFIRE

    Volar locking plate vs closed reduction and casting for distal radius fractures in adults 60 and over?

    Finding

    No clinically important difference in wrist function at 12 months, though patients rated surgery as more successful.

36. 2021
    TraumaNEJM

    REGAIN

    Spinal vs general anaesthesia for hip fracture surgery in previously ambulatory adults?

    Finding

    No difference in survival, walking, or delirium at 60 days, dismantling the observational case that regional anaesthesia protects the elderly hip.

37. 2021
    SpineNEJM

    NORDSTEN-DS

    Decompression alone vs decompression with instrumented fusion for stenosis with degenerative spondylolisthesis of 3 mm or more?

    Finding

    Decompression alone was non-inferior at 2 years and remained so at 5 — the pragmatic tiebreaker after Försth and SLIP disagreed.

38. 2022
    Hand & wristBMJ

    DRAFFT2

    K-wire fixation vs moulded cast after manipulation of dorsally displaced distal radius fractures?

    Finding

    Wrist function was the same at 12 months, but roughly one in eight cast patients needed later surgery for redisplacement.

39. 2022
    ArthroplastyJAMA

    CRISTAL

    Aspirin vs enoxaparin for VTE prophylaxis after hip or knee arthroplasty?

    Finding

    Aspirin failed non-inferiority, with significantly more symptomatic VTE at 90 days after primary joint replacement.

40. 2022
    Foot & ankleNEJM

    Myhrvold

    Non-operative treatment vs open repair vs minimally invasive repair for acute Achilles rupture?

    Finding

    Patient-reported outcomes were similar across all three arms at 12 months; reruptures were more frequent without surgery.

41. 2022
    TraumaLancetCanadian-led

    Aqueous-PREP

    Aqueous 10% povidone-iodine vs 4% chlorhexidine gluconate skin antisepsis for open fracture surgery?

    Finding

    No difference in surgical site infection — the companion to PREPARE under the same master protocol.

42. 2023
    TraumaNEJM

    PREVENT CLOT

    Aspirin vs enoxaparin for thromboprophylaxis after an operatively treated extremity fracture or any pelvic/acetabular fracture?

    Finding

    In the largest orthopaedic trauma trial ever run, aspirin was non-inferior for 90-day mortality with low event rates and no signal of harm.

43. 2024
    TraumaNEJMCanadian-led

    PREPARE

    Iodine povacrylex in alcohol vs chlorhexidine in alcohol for skin antisepsis before fracture surgery?

    Finding

    Iodine cut surgical site infection by roughly a quarter in closed fractures — a nearly free intervention — with no difference in open fractures.

44. 2026
    ArthroplastyNEJMCanadian-led

    EPCAT III

    Aspirin from day zero vs a 5-day rivaroxaban lead-in before aspirin after hip or knee arthroplasty?

    Finding

    Aspirin monotherapy was non-inferior in standard-risk patients; the low-risk cohort defines where aspirin alone is defensible rather than overturning CRISTAL.

45. 2026
    Arthroplastyconference report

    PEPPER

    Aspirin vs warfarin vs rivaroxaban for thromboprophylaxis after hip or knee replacement?

    Finding

    Interim reports suggest more VTE with aspirin and more bleeding with the anticoagulants; the definitive publication is still pending.

Brief takeaways simplify complex studies. Read the original trials before citing them in an examination or applying them in theatre.