Clinical trial NCT05389800: Pre- and Post-Operative Exercise in Patients With Hip Fracture
Official title: Pre- and Post-Operative Effects of Upper Extremity Aerobic Exercise in Mobility, Haemostatic Balance, and Mortality- and Morbidity-related Biomarkers in Hip Fracture Patients: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hip Fractures
Keywords: hip fracture
exercise therapy
surgical stress
haemostasis
basic mobility
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
First posted: 2022-05-25
Enrollment: 116
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purposes of this study are to determine the benefits of a pre-operative aerobic exercise program and an 8-week postoperative aerobic exercise program with a portable upper extremity cycle-ergometer in patients with hip fracture.

Detailed description: Hip fracture is one of the primary causes of significant morbidity in those over than 65 years old. Hip fracture is also among the top ten causes of loss of disability-adjusted life years in elderly. For the year 2020, in terms of the percentage of population over 80 years, Greece was second among the countries of the European Union, with this age group constituting 7.2% of its total population. In Greece, between 1977 and 2007, hip fractures doubled, with the annual impact rising to 343.96 per 100,000 inhabitants. For this population, a critical part of management is physical activity and exercise prescription both to prevent complications and to enhance rehabilitation after surgery. Postoperative (post-discharge) aerobic exercise programs of moderate intensity have already been used in patients with hip fracture proving its safety and positive effect in a variety of outcomes, such as aerobic capacity and quality of life. It is well established that these patients do not meet the minimum least amount of activity that should be done per week, based on Guidelines for Physical Activity by the World Health Organization neither during their hospitalization nor during their later life in the community. Also, although most Clinical Guidelines recommend a surgical management within 48 hours after hip trauma, there are many patient and system factors which can contribute to delayed surgery, such as surgical readiness, available resources, prioritisation and out-of-hours admission.

In terms of pre-operative exercise program, the investigators hypothesize that it will reduce surgical stress through the body's better response to lactate accumulation and the acute physiological effects on the patient's hematopoietic activity and hemostatic profile. Moderate intensity exercise will reduce platelet hyperactivity, increase fibrinolytic activity and reduce coagulation factors. In this more favorable environment, the immediate postoperative recovery of basic mobility can be accelerated. Regarding the post-operative exercise program, the investigators hypothesize that it will improve the independence and function of the lower extremity by increasing the cardiopulmonary capacity, while the improvement of the nutritional factors (albumin and pre-albumin) through the post-training protein synthesis will also contribute to this.

Apart from primary and secondary outcomes, at baseline the investigators will also evaluate the following: demographics; characteristics about the fracture and upcoming surgery, such as the type of fracture and the surgical procedure; New Mobility Score (NMS) to define the prefracture functional level; Addenbrooke's Cognitive Examination - III (ACE-III) to define the cognitive status.

The power analysis for the selection of the sample size for the postoperative program in the change of the 6-Minute Walk Test (primary outcome) after the completion of the program, in the 8 weeks postoperatively, was performed for significance level α = 0.05 and power = 90%.The investigators' assumption for power analysis stands to find a difference of 50 meters between the groups. Considering that the ratio between the groups will be 1: 1, the required sample size is 96 patients (48 in each group). Adding a drop-out rate of 20%, required sample size is defined in 116 patients (58 in each group). About the other primary outcome (postoperative 3-day Cumulated Ambulation Score - CAS), the investigators' power analysis revealed a required sample size of 80 patients, based on the assumptions of 2.4 points difference between the groups, α = 0.05 and power = 90%. In statistical analysis, only patients who completed at least a 3 days of preoperative program will be included.

Eligibility criteria: Inclusion Criteria:

* Age: 65 years old and older
* Unilateral proximal femoral fracture/hip fracture (intertrochanteric or neck fracture)
* Ambulatory patients before fracture (with or without aid assistance)
* Agreed to participate and signed consent form

Exclusion Criteria:

* Pathological fractures (under musculoskeletal oncology)
* Severe neuropsychiatric disorder (eg severe psychiatric disorder, dementia, etc.) to the extent that the researcher deems the patient incompetent or likely unable to remain compliant with the follow-up
* Unable to implement the exercise program due to underlying pathology or disability in the upper extremities
* More than one fracture
* Severe and / or unstable cardiovascular disease \[e.g. congenital heart disease, uncontrolled severe hypertension (systolic blood pressure ≥ 180 mmHg and / or diastolic blood pressure ≥ 120 mmHg), unstable angina\]
* Neurological or other conditions that significantly impair function and independence (eg stage 3-5 Parkinson's disease according to Hoehn and Yahr, advanced Multiple Sclerosis, severe arthritis of degenerative or rheumatic etiology)
* Severe metabolic bone disease (eg Paget's disease, renal bone disease, osteomalacia), excluding osteoporosis
* Active deadly aggressive disease (eg end-stage cancer with an estimated survival expectancy of less than 6 months)
* Unable to understand the consent document and / or protocol instructions
* Refusal to participate in the research

Primary outcomes:
measure: Cumulated Ambulation Score
timeFrame: Total 3-day Cumulated Ambulation Score post-operatively.
measure: Six Minute Walk Test (6MWT)
timeFrame: 8 weeks post-operatively
Secondary outcomes:
measure: Cumulated Ambulation Score
timeFrame: 4 weeks post-operatively
measure: Six Minute Walk Test (6MWT)
timeFrame: 4, 26 & 52 weeks post-operatively
measure: Timed-Up & Go
timeFrame: 4, 8, 26 & 52 weeks post-operatively
measure: Modified Harris Hip Score
timeFrame: At admission (for pre-operative status) and 4, 8, 26 & 52 weeks post-operatively (for current status)
measure: Lower Extremity Functional Scale
timeFrame: At admission (for pre-operative status) and 4, 8, 26 & 52 weeks post-operatively (for current status)
measure: Lactate levels
timeFrame: Day 0 (at admission), Intraoperatively (at the beginning, 30 minutes later, and at the end of the surgery), & 12h postoperatively
measure: Albumin levels
timeFrame: First day of admission, one day before surgery, 3 days, 4, 8, 26 & 52 weeks post-operatively
measure: Tissue plasminogen activator
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: Plasminogen activator inhibitor-1
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: Thrombin-Antithrombin Complex
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: Endogenous Thrombin Potential
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: Fibrinogen plasma levels
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: D-Dimers plasma levels
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: Thrombomodulin plasma levels
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: von Willebrand factor (VWF); VWF:Antigen and VWF:Activity plasma levels
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: Haemostatic profile using ROTEM
timeFrame: First day of admission, one day before surgery, 3 days, 1, 4, 8, 26 & 52 weeks post-operatively
measure: Transfusion requirements (litre)
timeFrame: Post-operative day 1, 2 and 3
measure: Deep vein thrombosis & Pulmonary embolism (DVT & PE)
timeFrame: 4, 8, 26 & 52 weeks post-operatively
measure: Re-admission
timeFrame: 4, 8, 26 & 52 weeks post-operatively
measure: All-cause mortality
timeFrame: 4, 8, 26 & 52 weeks post-operatively
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 1st Department of Orthopaedic Surgery, Medical School, National and Kapodistrian University of Athens
state: Attiki
Study officials:
affiliation: 1st Department of Orthopaedic Surgery, National and Kapodistrian University of Athens
name: Panagiotis Koulouvaris, MD
role: PRINCIPAL_INVESTIGATOR
References: