Femoral Nerve Block Versus Intravenous Fentanyl for Pain Management in Emergency Department Patients With Hip Fracture: A Randomized, Double-Blind, Clinical Trial
Phase: PHASE4
Conditions: Hip Fractures, Analgesia, Femoral Nerve
Sponsor: Marmara University

NCT06862154 
25.04.2022 
Comparison of the Efficiency of Femur Nerve Block and Intravenous Analgesia 
Treatment in Hip Fracture Patients 
 
MATERIALS AND METHODS 
Design and Setting 
This was a prospective, double-blind, randomized, single-center superiority trial with a 1:1 
parallel-group design, conducted in an academic ED. Ethical approval for this study was 
obtained from the local ethics committee and the institutional review board (approval no: 
09.2022.604, Marmara University Faculty of Medicine Clinical Research Ethics Committee). 
The study was conducted in accordance with the ethical standards of the Declaration of Helsinki 
and relevant local regulations. We used the CONSORT checklist when writing our report. 
Study Population, Inclusion, and Exclusion Criteria 
All consecutive adult patients (aged ≥18 years) presenting to our ED between November 2022 
to December 2024 with a radiologically verified hip fracture were screened for inclusion based 
on the following criteria: (i) diagnosed with a unilateral fracture of the femoral neck or proximal 
femur via radiological evaluation; (ii) provision of informed consent by the patient, a relative, 
or a legal guardian. 
The exclusion criteria were as follows: (i) hemodynamic instability or requiring urgent 
intervention for trauma; (ii) concomitant fractures; (iii) INR ≥2.5 or at risk of hemorrhage; (iv) 
received analgesics or a nerve block to the affected area prior to arrival at the ED; (v) allergy 
to local anesthetic agents or fentanyl; (vi) pregnancy; (vii) periprosthetic fracture; (viii) 
peripheral neuropathy. 
Randomization and Allocation Concealment 

NCT06862154 
25.04.2022 
Patients who met the inclusion/exclusion criteria were enrolled and randomly assigned in a 1:1 
ratio to receive either FNB or fentanyl therapy. Randomization was performed using a 
computer-generated sequence with blocks of six to ensure a balanced allocation of groups. The 
allocation sequence of patients was concealed using consecutively numbered and sealed 
envelopes. A non-blinded investigator performed the randomization. 
Masking  
In accordance with the methodology of the study, the attending physician, nurses, treatment 
team, and participants were blinded using the following protocol: 
To blind the treatment allocation, each participant was administered intravenous (IV) treatment 
and femoral nerve injection concurrently, with one group receiving a placebo in lieu of the IV 
analgesic and the other group receiving a placebo in place of the FNB. FNB was administered 
as 20 mL of 0.5% bupivacaine or a placebo (20 mL of 0.9% normal saline) filled into a syringe. 
The intravenous analgesic was administered as fentanyl at a dosage of 1 mcg/kg. (This was 
created by drawing 100 mcg of fentanyl into the syringe and diluting it with 100 mL of 0.9% 
sodium chloride solution.) The placebo consisted 100 mL of 0.9% normal saline solution. 
Syringes and serum set for FNB and IV treatment were prepared by a non-blinded investigator 
according to the instructions. The syringes were labeled with the designations "Syringe A" and 
"Syringe B," while the serum sets were labeled "Set A" and "Set B." Syringes and sets prepared 
with application instructions were given to the team administering the treatment according to 
the randomization order (A or B). The application instructions delineated the protocol for the 
administration of FNB and IV treatment, enumerating the sequence in which the respective 
procedures were to be executed. For example, "Initially, administer the medication in syringe 
B for FNB." Administer the drug in Set B for intravenous analgesic treatment at a dosage of 1 
cc per kilogram to the patient. 

NCT06862154 
25.04.2022 
Data Collection 
Vital signs, chronic diseases and demographic data about the patients were documented at the 
time of admission. Pain scores were recorded by nurses, blinded to the treatment groups, just 
before to the initiation of therapy and 20 minutes post-treatment completion.  
Cognitive functions of participants were evaluated utilizing the Glasgow Coma Scale (GCS) 
and the Abbreviated Mental Test 4 (AMT-4). The Numeric Pain Rating Scale (NPRS) was 
employed for patients capable of verbally rating their pain (GCS was 15 and AMT-4 ≥8) on a 
scale of 0 to 10, whilst the Pain Assessment in Advanced Dementia Scale (PAINAD) was 
utilized to evaluate pain in individuals with cognitive impairment (GCS <15 or AMT-4 <8). 
This guaranteed that all participants obtained a uniform score ranging from 0 to 10. 
We also followed whether patients needed rescue analgesia (IV fentanyl, tramadol or morphine) 
within four hours after the end of treatment. 
FNB procedure 
The femoral nerve block (FNB) was performed by three researchers who had training in this 
domain and a minimum of two years of practical experience in its implementation. 
Patients were placed in the supine position. Following preparation and the administration of 
local anesthesia, 20 mL of 0.5% bupivacaine or 20 mL of 0.9% normal saline as a placebo was 
injected into the region utilizing a high-frequency linear probe under ultrasound guidance. The 
nerve was recognized as an echogenic triangular region lateral to the femoral vein. An ultrasonic 
needle sized 22G x 50 mm (SonoPlex STIM; PAJUNK GmbH, Geisingen, Germany) was 
placed by the Seldinger technique until its tip was positioned near to the femoral nerve. 
Following the confirmation of negative aspiration, a small-volume injection was administered, 
and the expansion of the nerve sheath was visualized on the monitor as the fluid infused. 
Subsequently, the entire 20 mL was administered to finalize the treatment. Throughout the 

NCT06862154 
25.04.2022 
process, blood pressure, heart rate, respiration rate, and arterial oxygen saturation were 
observed. 
Outcomes 
The primary outcome of the study was the change in pain intensity from baseline to 20 minutes 
after the intervention. The secondary outcomes included the need for rescue analgesia and the 
occurrence of adverse events. 
Sample size estimation 
The sample size was calculated to obtain a statistically significant difference between the two 
groups in the change in the pain scale at 20 minutes after treatment, which was our primary 
endpoint in comparing the analgesic efficacy of FNB and IV opioids in patients with hip 
fractures. To demonstrate this difference with 90% power, we determined the sample size to be 
52 for each group, totaling 104, based on calculations from previous studies. Calculations were 
made with the G*Power program (Universitat Düsseldorf) 
Statistical analysis 
Analyses were conducted on an intention-to-treat (ITT) basis; subgroup analysis were also 
reported for comparison. No data was missing for the primary outcome. Baseline continuous 
variables were presented as mean (SD) or median (IQR), and categorical variables as n (%). 
The between-groups differences were calculated using the change of each group and reported 
as mean or median differences with 95% confidence intervals (CI). We considered differences 
statistically significant if the 95% CI did not cross zero. Effect sizes of differences and ratios 
were reported with their 95% CI. The accepted Type 1 error in this study was 5%. Graphs were 
produced using GraphPad Prism 10.4.1 (GraphPad Software Inc., San Diego, California). 
Statistical analyses were performed using Jamovi version 2.3.26 (The Jamovi Project, 
Australia).