Aggregometry in Elderlies With Hip Fracture and Receiving Clopidogrel

Anesthesia Clinical Trial

Official title:

Platelet Aggregometry to Drive the Surgical Timing in Elderlies With Hip Fracture and Receiving Clopidogrel.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04642209
• Other study ID #: Teg-Femur
• Status: Not yet recruiting
• Start date: December 1, 2020
• Est. completion date: December 30, 2020

Study information

• Verified date: November 2020
• Source: University Magna Graecia
• Contact: Federico Longhini, MD
• Phone: 00393475395967
• Email: longhini.federico[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In elderly patients, hip fracture should be surgically treated within 48 hours from admission, since its deferral worsens the mortality. However, sometimes patients are affected by cardiovascular or cerebral comorbidities, deeming necessary the use of antiplatelets and/or anticoagulant therapies. Clopidogrel is a second-generation thienopyridine antiplatelet drug which exerts its effect by the inhibition of the platelet's purinergic receptor P2Y12 preventing adenosine diphosphate (ADP) from stimulating it. Guidelines recommend to withhold clopidogrel for 5 days before the possibility to perform neuraxial anesthesia, which is frequently the optimal perioperative management of a fragile patient. It should be mentioned however that around 30% of patients are resistant to clopidogrel and they show a normal platelet reactivity despite the antiplatelet therapy. Therefore, in principle, these patients do not require to defer surgery. We have therefore hypothesized that some patients taking clopidogrel might anticipate surgery before 5 days and within 48 hours, following a protocol based on the assessment of coagulation and platelet aggregation through thromboelastography (TEG) in combination with an ADP Platelet Mapping assay kit.

After hospital admission for femur fracture, eligible patients would be evaluated by the anesthesiologist and the orthopedic physicians for anesthesia and surgery. Immediately a sample of blood should be collected for TEG with ADP Platelet Mapping test. If both MA-ADP and platelets aggregation (%) will be within normal values, the patient could be considered as candidate for immediate surgery (within 48 hours) with neuraxial anesthesia and ultrasound-guided antalgic femoral nerve block. If MA-ADP and/or platelets aggregation (%) are lower, risk for mortality should be assessed. If the patient would be considered at high risk for mortality, he/she would undergo to general anesthesia and peripheral antalgic block to not postpone surgery. Otherwise, surgery would be postponed until the normalization of both MA-ADP and platelet aggregation.

Description:

Hip fracture is an established and recognized health problem associated with the age of the population. In the elderly, it is essential that surgery for hip fractures would be performed within 48 hours from admission. Whenever delayed beyond 48 hours, the probability of 30-day mortality increases by 41% and the odds of one-year mortality by 32%.

Neuraxial anesthesia and/or peripheral nerve block are generally preferred in elderlies. However, cardiovascular and/or cerebral comorbidities require antiplatelets therapies at home. This treatment precludes the possibility of an optimal anesthesiologic strategy (i.e., loco-regional anesthesia) within the recommended surgical timing. Therefore, an individual approach is required to balance the risk of drugs continuation/cessation on major cardiovascular events and on peri-operative bleeding.

Clopidogrel is a second-generation thienopyridine antiplatelet drug, that exerts its effect by the inhibition of the platelet's purinergic receptor P2Y12, preventing adenosine diphosphate (ADP) from stimulating it. In patients needing surgery, guidelines recommend withholding clopidogrel 5 days before. However, around 30% of patients are resistant to clopidogrel for several reasons. Patients resistant to clopidogrel may be identify through the thromboelastography (TEG). TEG is a resonance-frequency viscoelastic point-of-care diagnostic system that assesses hemostasis and response to antiplatelet therapy, in combination with the ADP Platelet Mapping assay kit.

It has been hypothesized that the assessment of platelet aggregation with TEG and ADP Platelet Mapping may identify patients resistant to clopidogrel, not requiring to wait for 5 days for hip replacement surgery. We have therefore designed this protocol to guide anesthesiologists in the management of elderlies receiving clopidogrel and requiring surgery for hip fracture. The aim of this pilot study is to evaluate if in a small population of patients, our protocol based on platelet function monitoring would anticipate surgery within 48 hours at least in 70% of elderly patients receiving clopidogrel.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 9
• Est. completion date: December 30, 2020
• Est. primary completion date: December 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• all patients older than 65 years/old

• admission to the hospital for suspected traumatic femur fracture

• home therapy with clopidogrel 75 mg/die at home

Exclusion Criteria:

• pre-existing coagulopathies

• assumption of any anticoagulant oral therapy

• platelet count <100.000 mcL

• pre-existing liver disease

• known autoimmune diseases

• presence of hematological malignancies

Related Conditions & MeSH terms

• Anesthesia
• Clopidogrel, Poor Metabolism of
• Fractures, Bone
• Hip Fractures

Intervention

Device:
• Aggregometry
After evaluation at the Emergency Department the anesthesiologist immediately collects a sample of blood for TEG with ADP Platelet Mapping test. If both MA-ADP and platelets aggregation (%) are within normal values (i.e. =45 mm and =83%, respectively), the patient could be considered as candidate for immediate surgery (within 48 hours) with neuraxial anesthesia. If MA-ADP and/or platelets aggregation (%) are lower than normal values, the Nottingham Hip Fracture Score (NHFS) is computed, to predict the 30-day mortality after hip fracture surgery. If NHFS is =4 (high risk), the patient will undergo to general anesthesia and peripheral antalgic block, to perform surgery within 48 hours. In case of low risk for mortality (i.e. a NHFS <4), surgery will be postponed until the normalization of both MA-ADP and platelet aggregation.

Locations

Country	Name	City	State
Italy	Federico Longhini	Catanzaro

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Bottle A, Aylin P. Mortality associated with delay in operation after hip fracture: observational study. BMJ. 2006 Apr 22;332(7547):947-51. Epub 2006 Mar 22. — View Citation

Kristensen SD, Knuuti J, Saraste A, Anker S, Bøtker HE, De Hert S, Ford I, Gonzalez Juanatey JR, Gorenek B, Heyndrickx GR, Hoeft A, Huber K, Iung B, Kjeldsen KP, Longrois D, Luescher TF, Pierard L, Pocock S, Price S, Roffi M, Sirnes PA, Uva MS, Voudris V, Funck-Brentano C; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur J Anaesthesiol. 2014 Oct;31(10):517-73. doi: 10.1097/EJA.0000000000000150. Review. — View Citation

Price MJ, Walder JS, Baker BA, Heiselman DE, Jakubowski JA, Logan DK, Winters KJ, Li W, Angiolillo DJ. Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial. J Am Coll Cardiol. 2012 Jun 19;59(25):2338-43. doi: 10.1016/j.jacc.2012.02.042. — View Citation

Tarrant SM, Kim RG, McGregor KL, Palazzi K, Attia J, Balogh ZJ. Dual Antiplatelet Therapy and Surgical Timing in Geriatric Hip Fracture. J Orthop Trauma. 2020 Oct;34(10):559-565. doi: 10.1097/BOT.0000000000001779. — View Citation

Warlo EMK, Arnesen H, Seljeflot I. A brief review on resistance to P2Y(12) receptor antagonism in coronary artery disease. Thromb J. 2019 May 20;17:11. doi: 10.1186/s12959-019-0197-5. eCollection 2019. Review. — View Citation

Yang Z, Ni J, Long Z, Kuang L, Gao Y, Tao S. Is hip fracture surgery safe for patients on antiplatelet drugs and is it necessary to delay surgery? A systematic review and meta-analysis. J Orthop Surg Res. 2020 Mar 12;15(1):105. doi: 10.1186/s13018-020-01624-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients undergoing to hip replacement surgery	Number of patients undergoing to hip replacement surgery within 48 hours from hospital admission	within 48 hours from hospital admission
Secondary	Occurrence of peri or post-operative complications	Occurrence of peri or post-operative complications, such as postoperative myocardial infarction, thromboembolism, and postoperative confusion	28 days from admission
Secondary	Occurrence of intra-operative hypotension	Reduction of mean arterial pressure by 10% from baseline	During surgery
Secondary	Presence of post-operative bleeding	Presence of post-operative bleeding greater than 600 ml, considered as clinically relevant	Within 48 hours after surgery