Hip fracture Accelerated care and TreaTment trACK (HIP ATTACK)-2

Patients suffering a hip fracture with an acute myocardial injury are at
substantial risk for mortality. The current standard of care is to delay
surgery for those patients while additional tests and potential treatments are
implemented with the intention of minimizing the risk of post-operative
complications. However, there is no RCT data demonstrating that cardiac
stabilization and surgical delay are beneficial for these patients. Among the
patients with an acute myocardial injury randomized to standard care in the HIP
ATTACK-1 trial mortality was more than doubled as compared to patients that
underwent accelerated surgery.
There exists a strong biological rationale for how accelerated surgical
treatment of a hip fracture and an acute myocardial injury may lower a
patient*s risk of death. There is also encouraging data from HIP ATTACK-1 trial
suggesting that early surgery for a hip fracture reduces a patient*s risk of
mortality. Moreover, the HIP ATTACK-1 trial demonstrated the feasibility of a
trial comparing accelerated medical assessment and surgery versus standard care
in those patients. Currently, most patients wait more than 24 hours to have
surgery after diagnosis of a hip fracture when there is an ongoing myocardial
injury. The need for a large adequately powered trial to settle the issue in a
clear way that will drive subsequent practice is compelling.
This is the first large trial that may change the paradigm to postpone surgery
in patients suffering acute myocardial injuries before surgery, proposing a
novel approach to reverse myocardial injury through expedited surgical care.

In patients diagnosed with a hip fracture who also have acute myocardial injury
on presentation to hospital, is accelerated surgery superior to standard care
for the primary outcome of death at 90 days after randomization?

The HIP ATTACK-2 trial is an investigator-initiated, multicentre,
international, open-label, RCT that will include 1100 patients presenting with
a hip fracture and an acute heart injury. Patients will be randomized to
accelerated medical assessment and surgical repair (i.e., goal of surgery
within 6 hours of hip fracture diagnosis) or standard care (i.e., medical
management of the heart injury and then surgery when the acute heart injury has
stabilized). We hypothesize that accelerated surgery is superior to medical
management for the primary outcome of death at 90 days after randomization.

The planned trial intervention consists of accelerated medical clearance and
surgery (i.e., goal of surgery within 6 hours of hip fracture diagnosis). Our
objective with accelerated surgery is to facilitate surgery as quickly as
possible. We have selected a goal of 6 hours because we know this is a
substantial improvement beyond standard care and achieving this target is
feasible, based on the HIP ATTACK-1 trial. The control group will receive
standard care (i.e., medical management and cardiac stabilization of the
myocardial injury, and performing surgery according to usual timing based on
local institution practices), usually >24 hours after the hip fracture
diagnosis.
Patients randomized to accelerated care will undergo medical clearance by a
dedicated HIP ATTACK-2 medical specialist (e.g., medical specialist would
include internal medicine specialist, perioperative care physician,
cardiologist, or anaesthetist), who will be available to quickly arrive in the
ED 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-2 specialist will assess patients regarding
ongoing cardiovascular symptoms (e.g., chest pain), ECG ischemic changes, signs
of acute congestive heart failure or cardiogenic shock. After medical
clearance, the orthopedic surgeon and anaesthesiologist have to agree that the
patient is appropriate for surgery in order for the case to proceed. Patients
randomized to accelerated care who are receiving therapeutic dose vitamin K
antagonist anticoagulant will receive Prothrombin Complex Concentrate, where
available and appropriate.
Patients randomized to accelerated care, after obtaining medical clearance,
should be accommodated into the next orthopedic operating room slot.
Immediately after medical clearance is obtained, research personnel will inform
all the relevant stakeholders (i.e., surgical booking clerk, orthopedic
surgeon, and anesthesiologist).
Patients randomized to standard care will undergo medical management of the
acute myocardial injury based on local standard practices. The medical
management may include medical management of the acute myocardial injury (e.g.,
aspirin, statin, beta-blockers, ACE inhibitors), additional tests and
observation of the heart injury (e.g., serial troponin measurements, serial
ECGs, preoperative Echocardiogram), and then hip surgery when the acute heart
injury has stabilized (i.e., typically >24 hours after diagnosis). After the
patient is medically cleared, they will be waitlisted for surgery according to
local standard care.

There is a potential risk that accelerated surgery patients may have another
preoperative acute medical condition missed that could benefit from medical
optimization before surgery (Appendix 2 presents a list of acute medical
conditions likely to benefit from medical optimization prior to surgery). For
example, the myocardial injury could be in fact a high-risk acute coronary
syndrome (i.e., acute myocardial infarction with a mechanical complication
[i.e., acute papillary muscle rupture, ventricular septal defect], ST-elevation
myocardial infarction, cardiogenic shock) that may benefit from medical
optimization. We specified these conditions as one of the exclusion criteria
for the trial. The same HIP ATTACK-1 protocol will be implemented where at each
site a medical specialist will clear the patient before surgery, and the
anaesthesiologist and the surgeon will have to also approve these patients for
surgery.
In HIP ATTACK-1 only 9 of the 2970 patients had an acute severe medical
condition from hospital arrival to randomization (i.e., acute myocardial
infarction with a mechanical complication, ST-elevation myocardial infarction,
cardiogenic shock, stroke, subarachnoid hemorrhage, pulmonary embolus, coronary
revascularization, any condition resulting in dialysis, presumptive bacteremia,
and respiratory failure requiring mechanical ventilation). Moreover, a
pre-specified subgroup analysis did not demonstrate association with higher
mortality (HR 0.92; CI 95% 0.73-1.16 in patients with no acute medical
condition vs. HR 0.34; CI 95% 0.03-3.41 in patients with acute medical
condition; p value for interaction 0.36) or a composite of major complications
comparing patients in the accelerated care group and standard care group (HR
0.98; CI 95% 0.84-1.14 in patients with no acute medical condition vs. HR 0.30;
CI 95% 0.03-2.75 in patients with acute medical condition; p value for
interaction 0.19). A post-hoc subgroup analysis including an expanded list of
acute medical conditions demonstrated similar results for mortality (HR 0.91;
CI 95% 0.71-1.16 in patients with no expanded acute medical condition vs. HR
0.82; CI 95% 0.41-1.66 in patients with expanded acute medical condition; p
value for interaction 0.78), or for a composite of major complications
comparing patients in the accelerated care group and standard care group (HR
0.96; CI 95% 0.82-1.13 in patients with no expanded acute medical condition vs.
HR 1.00; CI 95% 0.57-1.73 in patients with expanded acute medical condition; p
value for interaction 0.93).
Patients randomized to standard care will receive care according to usual local
practices, and as such these patients are not at increased risk of
complications compared to patients not participating in the trial.