Landmark trials
The permanent backlist: trials that changed (or refused to change) orthopedic practice, in chronological order.
2001 · Spine · Spine: low back pain
Fritzell
Lumbar fusion vs non-surgical care for chronic low back pain?
Fusion modestly reduced pain and disability at two years, though the non-operative comparator was weak.
2002 · NEJM · Trauma: limb salvage
LEAP
Limb salvage vs amputation after severe lower extremity trauma?
Two-year function was equivalent either way, and injury severity scores could not predict which limbs to salvage.
2002 · NEJM · Sports: knee
Moseley
Arthroscopic debridement or lavage vs placebo surgery for knee osteoarthritis?
Arthroscopy was no better than sham at any point over two years, ending its routine use for osteoarthritis.
2006 · JAMA/NEJM · Spine: lumbar
SPORT
Surgery vs non-operative care for disc herniation, spinal stenosis, and degenerative spondylolisthesis?
Heavy crossover blurred the intention-to-treat result; as-treated analyses favoured surgery, most clearly for stenosis and spondylolisthesis.
2007 · NEJM · Spine: sciatica
Peul
Early surgery vs prolonged conservative care for severe sciatica of 6–12 weeks?
Early surgery relieved leg pain faster, but outcomes were equivalent by one year; waiting cost time, not outcome.
2007 · JBJS · Trauma: clavicle · 🇨🇦 Canadian-led
COTS
Plate fixation vs sling for completely displaced midshaft clavicle fractures?
Plating reduced nonunion and symptomatic malunion, though later trials tempered how much function that actually buys.
2008 · JBJS · Trauma: tibia · 🇨🇦 Canadian-led
SPRINT
Reamed vs unreamed intramedullary nailing for tibial shaft fractures?
Reamed nailing reduced reoperations in closed fractures; no advantage in open fractures.
2008 · NEJM · Sports: knee · 🇨🇦 Canadian-led
Kirkley
Arthroscopic lavage and debridement plus optimised physical and medical therapy vs the therapy alone for knee osteoarthritis?
Arthroscopy added nothing to optimised non-operative care at two years — the active-comparator complement to Moseley that ended arthroscopy for knee OA.
2009 · NEJM · Spine: osteoporotic fracture
Vertebroplasty sham trials
Vertebroplasty vs a sham procedure for painful osteoporotic vertebral compression fractures?
Two simultaneous blinded trials found no benefit over sham out to six months; patient selection remains contested.
2010 · Lancet · Trauma: resuscitation
CRASH-2
Tranexamic acid vs placebo in bleeding trauma patients?
TXA cut all-cause mortality without excess thrombosis, with the benefit concentrated within three hours of injury.
2010 · NEJM · Sports: knee
KANON
Early ACL reconstruction plus rehabilitation vs rehabilitation with optional delayed reconstruction?
Outcomes matched at 2 and 5 years; over half the reconstructions could have been avoided.
2010 · JBJS · Foot & ankle · 🇨🇦 Canadian-led
Willits
Operative vs non-operative treatment of acute Achilles rupture with accelerated functional rehabilitation?
With early functional rehab, non-operative care matched surgery and rerupture rates were far closer than historically taught.
2011 · NEJM · Trauma: hip
FOCUS
Liberal (10 g/dL) vs restrictive (8 g/dL or symptoms) transfusion threshold after hip fracture surgery?
The restrictive threshold matched liberal transfusion for death and walking ability at 60 days, and most restrictive-arm patients avoided transfusion entirely.
2013 · NEJM · Sports: knee
FIDELITY
Arthroscopic partial meniscectomy vs sham surgery for degenerative meniscal tears?
Meniscectomy was no better than sham surgery, a landmark for surgical placebo effects.
2013 · NEJM · Sports: knee
METEOR
Surgery vs physiotherapy for meniscal tear with knee osteoarthritis?
No significant functional difference at 6–12 months, though many PT patients crossed over.
2013 · Ann Intern Med · Arthroplasty: VTE · 🇨🇦 Canadian-led
EPCAT I
After ~10 days of dalteparin following THA, extend prophylaxis with aspirin or continued dalteparin?
Aspirin was non-inferior for symptomatic VTE, legitimising aspirin as extended prophylaxis — though enrolment stopped short of the planned 1,100.
2014 · BMJ · Hand & wrist
DRAFFT
K-wires vs volar locking plates for dorsally displaced distal radius fractures?
No difference in patient-reported wrist function at 12 months; wires were cheaper.
2015 · JAMA · Shoulder & elbow
PROFHER
Surgical vs nonsurgical treatment for displaced proximal humerus fractures?
No difference in patient-reported outcomes over two years.
2015 · NEJM · Trauma: open fractures · 🇨🇦 Canadian-led
FLOW
Irrigation pressure and soap vs saline for open fracture wounds?
Very low pressure was acceptable; soap led to more reoperations than saline.
2015 · NEJM · Arthroplasty: knee
Skou
Total knee replacement plus 12 weeks of non-surgical treatment vs the non-surgical treatment alone?
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.
2016 · NEJM · Spine: stenosis
Försth
Decompression plus fusion vs decompression alone for lumbar stenosis, with or without degenerative spondylolisthesis?
Fusion added blood loss and operating time but no clinical benefit at 2 or 5 years.
2016 · NEJM · Spine: stenosis
SLIP
Laminectomy plus fusion vs laminectomy alone for grade I degenerative spondylolisthesis?
Published beside Försth with the opposite conclusion: fusion modestly improved SF-36 physical scores and markedly reduced reoperation.
2017 · Lancet · Trauma: hip · 🇨🇦 Canadian-led
FAITH
Sliding hip screw vs cancellous screws for femoral neck fractures?
No overall difference in reoperation at 24 months between fixation strategies.
2018 · Lancet · Shoulder & elbow
CSAW
Arthroscopic subacromial decompression vs placebo arthroscopy for shoulder impingement?
Decompression offered no meaningful benefit over placebo surgery.
2018 · JAMA · Trauma: open fractures
WOLLF
Negative pressure wound therapy vs standard dressings for severe open lower limb fractures?
No difference in disability at 12 months.
2018 · NEJM · Arthroplasty: VTE · 🇨🇦 Canadian-led
EPCAT II
After 5 days of rivaroxaban following hip or knee arthroplasty, extend prophylaxis with aspirin or continued rivaroxaban?
Aspirin was non-inferior for VTE at 90 days, making the short-DOAC-then-aspirin switch mainstream — though everyone got rivaroxaban first.
2019 · NEJM · Infection: bone & joint
OVIVA
Oral vs intravenous antibiotics for the first 6 weeks of treating bone, joint, or metalware-associated infection?
Oral therapy was non-inferior for treatment failure at one year, overturning a parenteral-only standard traceable to 1970.
2019 · NEJM · Arthroplasty: hip · 🇨🇦 Canadian-led
HEALTH
Total hip arthroplasty vs hemiarthroplasty for displaced femoral neck fractures?
No significant difference in secondary procedures at 24 months; modest functional gains with THA.
2019 · Lancet · Arthroplasty: knee
TOPKAT
Total vs partial knee replacement for isolated medial compartment osteoarthritis?
Both were effective at 5 years; partial replacement was cost-effective with similar outcomes.
2020 · NEJM · Spine: sciatica · 🇨🇦 Canadian-led
Bailey
Microdiscectomy vs 6 months of standardised non-operative care for sciatica already persisting 4–12 months?
Once symptoms were established beyond a few months, surgery genuinely outperformed continued conservative care — the chronic counterpart to Peul.
2020 · Lancet · Trauma: hip · 🇨🇦 Canadian-led
HIP ATTACK
Accelerated surgery (within ~6 h) vs standard care for hip fracture?
Accelerated surgery did not reduce mortality or major complications versus standard timing.
2020 · Lancet · Shoulder & elbow
UK FROST
Capsular release vs manipulation under anaesthesia vs structured physiotherapy for frozen shoulder?
No option was clearly superior; manipulation was the most cost-effective.
2020 · Lancet · Foot & ankle
UKSTAR
Plaster cast vs functional brace for non-operatively treated Achilles rupture?
Early weight-bearing in a functional brace matched casting at nine months and was safe.
2020 · Plast Reconstr Surg · Hand & wrist
WRIST
Volar plate vs external fixation vs pinning vs casting for distal radius fractures in adults 60 and over?
The plate recovered faster early but all arms converged by 12 months; cast malunion did not translate into worse function.
2021 · JAMA Surgery · Hand & wrist
CROSSFIRE
Volar locking plate vs closed reduction and casting for distal radius fractures in adults 60 and over?
No clinically important difference in wrist function at 12 months, though patients rated surgery as more successful.
2021 · NEJM · Trauma: hip
REGAIN
Spinal vs general anaesthesia for hip fracture surgery in previously ambulatory adults?
No difference in survival, walking, or delirium at 60 days, dismantling the observational case that regional anaesthesia protects the elderly hip.
2021 · NEJM · Spine: stenosis
NORDSTEN-DS
Decompression alone vs decompression with instrumented fusion for stenosis with degenerative spondylolisthesis of 3 mm or more?
Decompression alone was non-inferior at 2 years and remained so at 5 — the pragmatic tiebreaker after Försth and SLIP disagreed.
2022 · BMJ · Hand & wrist
DRAFFT2
K-wire fixation vs moulded cast after manipulation of dorsally displaced distal radius fractures?
Wrist function was the same at 12 months, but roughly one in eight cast patients needed later surgery for redisplacement.
2022 · JAMA · Arthroplasty: VTE
CRISTAL
Aspirin vs enoxaparin for VTE prophylaxis after hip or knee arthroplasty?
Aspirin failed non-inferiority, with significantly more symptomatic VTE at 90 days after primary joint replacement.
2022 · NEJM · Foot & ankle
Myhrvold
Non-operative treatment vs open repair vs minimally invasive repair for acute Achilles rupture?
Patient-reported outcomes were similar across all three arms at 12 months; reruptures were more frequent without surgery.
2022 · Lancet · Trauma: open fractures · 🇨🇦 Canadian-led
Aqueous-PREP
Aqueous 10% povidone-iodine vs 4% chlorhexidine gluconate skin antisepsis for open fracture surgery?
No difference in surgical site infection — the companion to PREPARE under the same master protocol.
2023 · NEJM · Trauma: VTE
PREVENT CLOT
Aspirin vs enoxaparin for thromboprophylaxis after an operatively treated extremity fracture or any pelvic/acetabular fracture?
In the largest orthopedic trauma trial ever run, aspirin was non-inferior for 90-day mortality with low event rates and no signal of harm.
2024 · NEJM · Trauma: infection · 🇨🇦 Canadian-led
PREPARE
Iodine povacrylex in alcohol vs chlorhexidine in alcohol for skin antisepsis before fracture surgery?
Iodine cut surgical site infection by roughly a quarter in closed fractures — a nearly free intervention — with no difference in open fractures.
2026 · NEJM · Arthroplasty: VTE · 🇨🇦 Canadian-led
EPCAT III
Aspirin from day zero vs a 5-day rivaroxaban lead-in before aspirin after hip or knee arthroplasty?
Aspirin monotherapy was non-inferior in standard-risk patients; the low-risk cohort defines where aspirin alone is defensible rather than overturning CRISTAL.
2026 · conference report · Arthroplasty: VTE
PEPPER
Aspirin vs warfarin vs rivaroxaban for thromboprophylaxis after hip or knee replacement?
Interim reports suggest more VTE with aspirin and more bleeding with the anticoagulants; the definitive publication is still pending.
One-line takeaways are simplifications; read the trials themselves before quoting them in an exam or the OR.