HIP ATTACK Trial: Can we improve outcomes after a hip fracture with accelerated surgery? PJ Devereaux, MD, PhD

Transcription

1 HIP ATTACK Trial: Can we improve outcomes after a hip fracture with accelerated surgery? PJ Devereaux, MD, PhD

2 Disclosure Member of research group with policy of not accepting honorariums or other payments from industry for own personal financial gain Accept honorariums/payments from industry to support research endeavors and reimbursement of costs to participate in meetings Based on study questions I originated and grants I wrote I have received grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol- Myers Squibb, Covidien, Roche Diagnostics, Stryker, Octapharma

3 Background > 35,000 Canadians per year suffer hip fracture Poor outcomes and substantial cost Case Hip fracture trauma Immobilization Inflammation Stress Pain Bleeding Hypercoagulability Catabolism Pneumonia, VTE, Stroke, MI, disability, Death

4 Systematic review of observational data Systematic review & meta-analysis 5 observational studies (multivariable adjustment) 4,208 patients with hip fracture 721 deaths Early surgery various definitions across studies < 72 hrs, < 48 hrs, < 24hrs adjusted RR 0.81 (95% CI, )

5 Design RCT Patients Pilot RCT patients with hip fracture during working hours Intervention accelerated medical clearance and surgery versus standard care Objectives feasibility or recruitment feasibility of accelerated care

6 Results Randomized 60 patients 3 centres 100% f/u at 30 days Median time from Dx to Sx standard care 24.2 hrs accelerated care 6.0 hrs Main clinical outcome (composite of death, preop MI, MINS, stroke, PE, pneumonia, major bleed) standard care 47% accelerated care 30% 6

7 HIP ATTACK Trial Multicentre international 1000 patient RCT comparing accelerated surgical care versus standard care in hip fracture patients Will begin recruitment in early 2014 Please consider joining

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10 Are hip fractures medical emergencies? Acute condition Poor outcome Outcome improvement by rapid treatment Myocardial infarction Ischemic stroke Hip fracture?

11 Need for trial No progress in mortality in last 15 years Observational data suggest improved outcomes after early surgery Observational data may overestimate effect residual confounding Observational data may underestimate effect greatest impact after very early surgery

12 Secondary objectives Primary composite outcome at 30 days all cause mortality and nonfatal MI, MINS, PE, pneumonia, life threatening/major bleeding Individual outcomes at 30 days components of primary composite, CHF, new AF, nonfatal cardiac arrest, DVT, cardiac cath, PCI, CABG, other bleeding, AKI, sepsis, nursing home placement Functional outcomes FIM motor domain, short form SF-36, delirium, LOS

13 Revision to trial design After first 11 patients - revision to Tx pathway Initial Treatment Pathway Revised Treatment Pathway Hip Fracture Arrival to ER Diagnosis Medical Clearance Randomization Arrival in OR Hip Fracture Arrival to ER Diagnosis Randomization Medical Clearance Arrival in OR

14 Inclusion criteria age >45 years Eligibility criteria hip fracture requiring surgery diagnosed during working hours and weekday Exclusion criteria requiring urgent surgery (e.g., MVA) open hip fracture therapeutic dose anticoagulation with agent other than warfarin or UFH refusal to participate or prior enrollment

15 Patient follow-up Days 1-7 after randomization daily troponin daily CAMs Daily in hospital outcome events medications date of first mobilization date of discharge and location 30 day assessment FIM and short SF-36

16 Baseline characteristics Accelerated care Standard care (N=30) (N=30) Mean Age (SD) 79.5 (±9.5) 82.6 (±9.0) Female (n) 56.7 % (17) 70.0% (21)

17 Cardiovascular history Accelerated care (N=30) n (%) Standard care (N=30) n (%) History of Stroke 8 (26.7) 3 (10.0) History of TIA 0 (0.0) 2 (6.7) History of CAD 5 (16.7) 7 (23.3) History of Coronary 3 (10.0) 1 (3.33) Revascularization CABG < 6 months PCI < 6 months History of Aortic Stenosis 1 (3.3) 3 (10.0) Moderate to Severe (3.3)

18 Cardiovascular history (2) Accelerated care (N=30) n (%) Standard care (N=30) n (%) History of PVD 2 (6.7) 1 (3.3) History of Atrial Fibrillation 5 (16.7) 7 (23.3) Current Atrial Fibrillation 4 (13.3) 5 (16.7) History of CHF 2 (6.7) 1 (3.3) Current CHF 0 1 (3.3) History of DVT 1 (3.3) 4 (13.3) History of PE 0 0 Current Troponin T elevation 1 (3.3) 3 (10.0)

19 Other medical history Accelerated care (N=30) n (%) Standard care (N=30) n (%) History of Hypertension 20 (66.7) 21 (70.0) History of Diabetes 3 (10.0) 1 (3.3) History of COPD 3 (10.0) 3 (10.0) History of Pneumonia within month prior to randomization Current UTI (3.3) History of Renal Failure with Dialysis egfr <30 ml/min 4 (13.3) 3 (10.0) History of Dementia 6 (20.0) 4 (13.3)

20 Other medical history (2) Required assistance with ADL prior to fracture Use of walking aid prior to fracture Nursing home residence prior to fracture Median time (hours) from fracture to ED (IQR) Median time in hours from arrival to diagnosis (IQR) Accelerated care (N=30) n (%) Standard care (N=30) n (%) 8 (26.7) 10 (33.3) 14 (46.7) 15 (50.0) 6 (20.0) 6 (20.0) 1.9 ( ) 1.6 ( ) 2.9 ( ) 2.6( )

21 Baseline measurements Accelerated care (N=30) Standard care (N=30) Mean Pre-op Systolic BP Mean Pre-op Heart Rate Mean BMI (SD) 25.2 (±4.0) 24.5 (±5.0) 21

22 Surgical/anesthetic data Accelerated care (N=30) n (%) Standard care (N=30) n (%) Fracture Type Femoral Neck 17 (56.7) 14 (46.7) Intertrochanteric 12 (40.0) 13 (43.3) Subtrochanteric 1 (3.3) 3 (10.0) Surgery Performed Internal Fixation 17 (56.7) 16 (53.3) Arthroplasty 12 (40.0) 14 (46.7) Anesthetic * Neuroaxial 25 (83.3) 24 (80.0) General 4 (13.3) 6 (20.0)

23 Trial results

24 Recruitment f/u data N % Met eligibility outside study hours 342 Total patients eligible 82 Total patients randomized 60 Eligible not randomized Patient/family declined Physician declined participation Not identified pre-op >1 patient eligible on same working day Lost to Follow-up

25 Feasibility outcomes Centre Number patients eligible Number patients randomized Number months recruiting Recruitment rate (pts/month) JHCC SJHH SIOR, India Total

26 Feasibility outcomes Accelerated care median hours (IQR) Standard care median hours (IQR) Dx to clearance (2 hr target) 76.7% 20.0% Initial Pathway Dx to clearance (AC 6, SC 5) 1.0 ( ) 1.0 ( ) Revised Pathway Dx to clearance (AC 24, SC 25) 1.8 ( ) 4.5 ( ) Overall Dx to clearance 1.5 ( ) 3.4 ( )

27 Accelerated patients with primary clinical endpoint Time from fracture to randomization (hours) Time from randomization to surgery (hours) Number of days to primary event Mean (median) (11.1) (6.7) 5.3 (3.0)

28 Feasibility outcomes Accelerated care mean hours (n=3) Standard care mean hours (n=3) VKA only patients Dx to OR (AC 1, SC 3) day primary event rate (%) 100% (PE) 66.6% (MINS) VKA + Octaplex Patients Dx to OR (AC 2, SC 0) 8.4 N/A 30 day primary event rate (%) 0% 0%

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30 Individual clinical outcomes Accelerated Care Standard Care N % N % Death Vascular Non vascular Pre-op MI MINS Stroke Pulmonary embolism Pneumonia Major/life-threatening bleeding

31 Individual clinical outcomes Accelerated Care Standard Care N % N % New CHF Sepsis Nonfatal cardiac arrest New AF DVT New AKI and dialysis Cardiac catheterization PCI CABG

32 Individual clinical outcomes Accelerated Standard Care Care N % N % New nursing home admission Delirium within 7 days postrandomization Mean FIM score SF-36 Health Survey Mean Physical score Mean mental score

33 Individual clinical outcomes Accelerated Care Standard Care n Median Mean n Median Mean Time from Randomization to first Mobilization (days) Length of Critical Care stay Length of Hospital Stay Length of Rehab Stay Combined length of hospital/rehab stay

34 Pilot conclusions HIP ATTACK Trial is feasible 6-hour target between hip fracture diagnosis and surgery is feasible >18 hr separation between accelerated and standard care from Dx to Sx Acute conditions hindering immediate OR uncommon High incidence of clinical events Efficacy results in pilot underpowered but encouraging

35 Moving forward Need faster triage in ER Need continued access to octaplex Need to review mobilization standards post Sx Need to consider implications of expanded hrs Full trial Need 850 pts 14 sites 2.5 years recruitment CIHR grant strategize about local funding to initiate now

36 Discussion

37 30 Day primary events VKA + Octaplex (N=2) n VKA Only (N=4) n Primary Composite 0 3 All cause mortality 0 0 Myocardial Injury 0 2 Pulmonary embolism 0 1 Pneumonia 0 0 Bleeding 0 0 Stroke 0 0

38 VKA & Octaplex Timelines VKA + Octaplex (Acc. Care) Pt. 1 Pt. 2 VKA Only (Acc. Care) VKA Only (Std. Care) Pt. 1 Pt. 2 Pt. 3 Time from Dx to Sx 9 hrs, 26 min 7 hrs, 19 min 13 hrs, 11 min 25 hrs, 39 min 29 hrs, 0 min 49 hrs, 15 min