HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial

Each year, 35,000 Canadians and millions of adults worldwide suffer a hip
fracture. Hip fractures primarily occur in the elderly and have devastating
consequences. Patients suffering a hip fracture are at risk of developing
cardiovascular (e.g., myocardial infarction, stroke), venous thrombosis (e.g.,
pulmonary embolism), infectious (e.g., pneumonia, sepsis), and bleeding (e.g.,
life-threatening and major) complications. These complications can result in
death. After a hip fracture, the 30-day mortality rate is 7-10% and 90-day
mortality is 10-20%. Patients who survive to 30 days are at substantial risk of
disability. Even among patients who were community-dwelling prior to their hip
fracture 11% are bed-ridden, 16% are in a long-term care facility, and 80% are
using a walking aid at 1 year. The disability adjusted life-years lost as a
result of hip fractures ranks in the top 10 of all causes of disability
globally. Hip fractures also result in substantial costs; the annual economic
impact in Canada is estimated at over $1 billion. Despite the magnitude of this
problem, little progress has occurred in improving the outcome of patients
suffering a hip fracture.
A hip fracture initiates inflammatory, hypercoagulable, stress, and catabolic
states that can cause medical complications. Early surgical treatment will
reduce the time patients are exposed to these harmful states and therefore may
reduce the risk of medical complications and mortality. Furthermore, rapid
surgery may result in a shorter period of immobility, which may impact
functional outcomes and hospital costs. There is preliminary evidence that
suggests early surgical treatment of a hip fracture may improve patients*
outcomes; however, standard care is that most patients typically wait >24 hours
to have surgery. We will undertake a large international randomized controlled
trial (RCT) to assess the impact of accelerated medical clearance and surgery
versus standard care of hip fractures. We call this trial the HIP fracture
Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial.

Patients suffering a hip fracture are at substantial risk of serious
complications and mortality. Among the patients randomized to standard care in
our pilot RCT 13.3% died and 46.7% suffered a major perioperative complication
within 30 days of randomization. There exists a strong biological rationale for
how accelerated surgical treatment of a hip fracture may lower a patient*s risk
of a major complication, improve their functional outcome, and reduce their
length of hospital stay. These postulated benefits could accrue from reducing
the patient*s exposure to the inflammatory, hypercoagulable, stress, and
catabolic states induced by a hip fracture and accelerating their time to first
mobilization. There also exist encouraging observational data suggesting that
early surgery for a hip fracture reduces a patient*s risk of mortality.
Moreover, our pilot RCT demonstrates the feasibility of a trial comparing
accelerated medical assessment and surgery versus standard care. Currently,
most patients wait more than 24 hours to have surgery after a diagnosis of a
hip fracture. The need for a large adequately powered trial to settle the issue
in a clear way that will drive subsequent practice is compelling.

HIP ATTACK is an international RCT of 3000 patients with a hip fracture that
requires a surgical intervention. This trial will determine the effect of
accelerated medical clearance and accelerated surgery compared to standard care
on the 90-day risk of all-cause mortality and major perioperative complications
(i.e., a composite of mortality, nonfatal myocardial infarction, nonfatal
pulmonary embolism, nonfatal pneumonia, nonfatal sepsis, nonfatal stroke, and
nonfatal life-threatening and major bleeding).
Currently, across Canada, 80 to 90% of patients with a hip fracture undergo hip
surgery within 48 hours after the diagnosis. Therefore, to minimize the
variation in timing of surgery between centres, we will only include
international centres that have >80% of their hip fracture patients undergo
surgery within 48 hours. This will assure that the standard care group in all
centres will have comparable time to surgery. In the HIP ATTACK Pilot 86.7% of
the standard care patients had surgery within 48 hours of being diagnosed with
a hip fracture.
Notable aspects of HIP ATTACK include: (1) this study is using an RCT design,
whereas all the prior studies (excluding our pilot) have used observational
data to evaluate the impact of surgical timing on health outcomes in patients
with hip fractures. Moreover, many authors have suggested an RCT was not
possible or would not occur; however, our pilot has demonstrated such a trial
is feasible. (2) Most interventions evaluated in RCTs only target 1 mechanistic
state (e.g., hypercoagulable state). It is biologically plausible that
accelerated surgery will impact 4 mechanistic states (i.e., inflammatory,
hypercoagulable, stress, and catabolic) and may therefore result in a larger
effect size (i.e., hazard ratio <=0.70) than normally seen in most clinical
trials (i.e., hazard ratio >=0.75). (3) Simple entry criteria and recording only
essential baseline and outcome data ensures feasibility and will facilitate
rapid recruitment and completion. (4) International enrolment with broad
eligibility criteria will ensure widely applicable results. (5) The trial will
yield important results. If it demonstrates accelerated surgery is beneficial,
it will have immense public health implications given the millions of adults
annually who suffer a hip fracture. If the trial demonstrates accelerated
surgery is not beneficial, this will avoid the substantial system modifications
required to facilitate accelerated surgical access for hip fracture patients.

Patients randomized to accelerated care will undergo medical clearance by a
dedicated HIP ATTACK medical specialist (e.g., medical specialist would
include, internal medicine specialist, geriatrician, cardiologist,
anaesthetist), who will be available to quickly arrive in the emergency
department for the assessment. This specialist will use their own judgement
regarding management when considering any medical conditions that they
identify, and they will weigh the potential benefits of delaying surgery for
medical management versus the potential negative consequences of protracted
exposure to the inflammatory, hypercoagulable, stress, and catabolic states
associated with a hip fracture. The HIP ATTACK medical specialist will be aware
of all the conditions that the trial consensus group believes are likely to
benefit from medical optimization before surgery, listed in Appendix 1. After
medical clearance the orthopedic surgeon and anaesthesiologist have to also
agree that the patient is appropriate for surgery for the case to proceed.
Patients randomized to accelerated care (i.e., medical clearance and surgery)
who are receiving therapeutic dose vitamin K antagonist anticoagulant will
receive Prothrombin Complex Concentrate to target an INR <=1.5.
Patients randomized to accelerated care, after obtaining medical clearance,
will move into the next orthopedic elective operating room slot (i.e., they
will gain priority over scheduled elective cases). Immediately after medical
clearance is obtained, research personnel will inform all the relevant
stakeholders (i.e., surgical booking clerk, orthopedic surgeon, and
anesthesiologist) to facilitate the exchange of the elective and the
accelerated hip fracture cases. The scheduled elective cases will shift a slot
forward and will occur a few hours later than originally planned, and the final
scheduled elective case will occur after normal working hours.
Patients randomized to standard care will undergo medical clearance based on
local standard practices. After the patient is medically cleared they will be
waitlisted for surgery according to local standard care.
Surgeons* decisions around the choice of surgical implant will be left to their
discretion and modern implants will be used.

With accelerated medical assessment there is a potential risk that the medical
specialist will miss a medical condition that would benefit from medical
optimization prior to surgery. This did not occur in the pilot, and we will
attempt to minimize this risk through the following measures. At each site a
HIP ATTACK medical specialist is designated daily who has time to rapidly get
to the emergency department to perform a consult within 2 hours. Further, the
anaesthesiologist and surgeon have to also approve the patient for surgery.
Patients randomized to standard care are not at any increased risk as they will
receive care according to usual local practices.