Study design
This is a single-centered, randomized, placebo-controlled, double-blinded trial conducted at Kameda Medical Center, Japan. We obtained approval for this study from the hospital’s ethics committee (Kameda Medical Center Clinical Research Review Board; approval number: 22–024). This trial was also registered in the Japan Registry of Clinical Trials (register number: jRCT1031220294; first registration: August 26, 2022; https://jrct.niph.go.jp/en-latest-detail/jRCT1031220294). There is no plan to amend the study protocol, including eligibility criteria, outcomes, or analyses. This study has no financial support. All the research members involved in this study have no interests to declare.
The methods and results of this study will be reported according to the Standard Protocol Items: Recommendations for Interventional Trials 2013 statement (Additional file 1). The flow diagram for the trial is presented in Fig. 1.
Figure 1.
Title: The flow diagram of the trial.
Legend: PENG, pericapsular nerve group; Prehabilitation, preoperative rehabilitation.
Recruitment for this study began on November 2, 2022, and will continue through the end of 2025. The anticipated submission date for the primary trial manuscript is set for September 30, 2026.
Eligibility criteria
Inclusion criteria
Patients will be included if they: 1) are adults over the age of 20; 2) have a Garden classification 3 or 4 femoral neck fracture; 3) are scheduled to receive hip arthroplasty at Kameda Medical Center; and 4) have an American Society of Anesthesiologists physical status (ASA-PS) between I and III.
Exclusion criteria
Patients will be excluded if they: 1) have dementia, defined as scoring less than 3 points in the Mini-Cog test [12]; 2) have known allergies to local anesthetics; 3) have a history of hip arthroplasty at the injured extremity; 4) have an infection at the site where the PENG block will be performed; 5) are bedridden prior to the injury; 6) are diagnosed as a pathological femoral neck fracture; or 7) are assessed as inappropriate for participation at the discretion of the orthopedic surgeon.
Informed consent
and withdrawal
Patients will be assessed by the research members according to the eligibility criteria. Researcher members will provide full details of the trial both orally and in writing, including implications, possible adverse effects, and any risks to the eligible patients. If patients agree to participate, written consent will be obtained. All participants can withdraw from the trial at any time if they or their families request, or if there are any serious adverse events related to PENG block, including bleeding, infection, neuropathy, and local anesthetic intoxication.
Baseline assessment
After enrolment, all the participants will undergo a preintervention assessment that includes a medical record review, and scores of 1) the motor part of the Functional Independence Measure (FIM) [13]; 2) Barthel Index [14]; 3) EuroQol 5 Dimension Self-Report Questionnaire (EQ-5D) [15].
Interventions
PENG group
The patients allocated in the PENG group will receive PENG block with a 20 ml solution of 0.375% ropivacaine. The PENG block will be scheduled at least one hour prior to the initial prehabilitation session. We will perform the blocks at the patient’s bedside, using the method described by Giron-Arango L, et al [7]. We will use a handheld portable ultrasound device (Vscan Air, GE Healthcare, Chicago, USA), consisting of linear (3–12 MHz) and curved (2–5 MHz) array transducer probes on each side of the device. This ultrasound device can be seamlessly connected to an electronic tablet via Bluetooth for real-time visualization.
No sedation will be given to patients during the block procedure. After skin sanitization, the procedure starts with local anesthesia with 2 to 5 ml of 1.0% lidocaine. Using either the linear or curved transducer of the ultrasound device, which is covered with a sterile ultrasound probe cover, we will place the ultrasound probe along the line running from the anterior inferior iliac spine (AIIS) to the pubic ramus. This will visualize the key anatomical structures, including the iliopubic eminence, the iliopsoas muscle, the iliopsoas tendon, and the femoral artery. Subsequently, we will insert a 22-gauge, either 50- or 80-mm needle (Stimuplex Ultra, B. Braun, Melsungen, Germany), placing its tip in the lower musculofascial plane of the iliopsoas muscle just above the pubic ramus. After ensuring negative aspiration, we will inject a 20 ml solution of 0.375% ropivacaine while continuously monitoring the spread of the solution through the real-time ultrasound view on the connected electronic tablet. We will save the images or videos of the solution’s distribution for reference.
Every PENG block will be administered by board-certified anesthesiologists, or anesthesiology residents who have substantial expertise in performing PENG blocks. For residents, the whole procedure will be under the direct supervision of an experienced board-certified anesthesiologist, ensuring both the safety and efficacy of the block administration.
Placebo group
The patients allocated in the placebo group will receive the PENG block with a 20 ml solution of normal saline placebo, instead of 0.375% ropivacaine.
Prehabilitation
Following hospitalization, the physical therapy team will promptly schedule prehabilitation sessions, usually on the day of admission or the following day, excluding Sundays and holidays. Daily sessions lasting 40 to 60 minutes will be conducted until surgery. The prehabilitation program comprises five items, with each subsequent item incrementally more challenging than the preceding one:
1) Bed-sitting: Sitting up on the bed.
2) Edge-sitting: Sitting up on the edge of the bed.
3) Stand-up: Rising from the bed.
4) Maintaining-standing: Maintaining a standing position.
5) Wheelchair-transfer: Transferring to wheelchair.
During each session, a single physical therapist will guide and assist the patient through the program sequentially. Prehabilitation will be terminated and will not proceed to the subsequent item if the patient is unable to perform, requests a stop,
experiences intolerable pain or meets predefined discontinuation criteria [16].
Pain management
All patients will receive a standardized pain management protocol during their hospitalization, including the prescription of common medications such as acetaminophen, nonsteroidal anti-inflammatory drugs, and tramadol. We will not use strong opioids or any form of patient-controlled analgesia.
Surgical intervention
The participants in this study will undergo standard surgical treatment, with the surgery scheduled as early as possible, following the current guidelines. It is crucial to note that this study will not interfere with the surgical schedules.
Anesthesia management
The anesthesia plan will be determined by the anesthesiologists’ discretion. Typically, we will employ spinal anesthesia or general anesthesia, with options of preoperative neural blocks including FNB, FICB, PENG block, and lateral cutaneous femoral nerve block.
Postoperative rehabilitation
Patients will receive postoperative rehabilitation from postoperative day 1. Daily sessions, lasting 40 to 60 minutes, will continue until the patient’s discharge. During each session, the physical therapist will provide the same content as prehabilitation, using the predefined prehabilitation program. Postoperative rehabilitation will be discontinued if the patient experiences intolerable pain or meets the predefined discontinuation criteria [16].
Outcome measurement
The primary outcome of this study is the percentage of patients who complete the entire prehabilitation program during the initial prehabilitation session. The secondary outcomes are shown in Table 1.
Table 1
| Outcomes during the initial prehabilitation session |
| (1) | Achievement of each item in the prehabilitation program |
| (2) | NRS pain score |
| Surgery-related outcomes |
| (1) | Intraoperative bleeding amounts |
| (2) | Thromboembolic events from postoperative day 0 to 7 |
| Postoperative outcomes (i) In patients undergoing surgery within 48 hours of admission (ii) In patients undergoing surgery more than 48 hours of admission |
| (1) | Postoperative 3-day cumulative CAS score |
| (2) | CAS score at discharge |
| (3) | Discharge destination (i) Home (ii) Nursing home or other location |
NRS, Numerical Rating Scale; CAS, Cumulated Ambulation Score [17, 18]
Sample size calculation
In our pilot study, approximately 70% of the patients received PENG block and 20% of the patients with standard pain management achieved the primary outcome. Considering the potential biases in the pilot study, we hypothesized 50% of those in the PENG group and 20% of those in the placebo group will achieve the primary outcome. By setting a statistical power of 80% and a significance level (α) of 0.05 to identify this difference, we calculated a sample size of 78. Allowing a potential 20% follow-up and data loss, we plan to randomize 100 patients (50 patients in each group).
Recruitment
All participants will be recruited during the period between the time of presentation and the start of the initial prehabilitation session from Kameda Medical Center, a tertiary hospital in Chiba Prefecture, Japan. After prehabilitation is prescribed by the orthopedic surgeons, the physical therapy team will identify potential participants and notify the research team. For potentially eligible patients, a research member will assess the eligibility, provide a detailed explanation of the study, conduct a screening evaluation, and seek written informed consent from the patient to obtain their permission to participate in the study.
Randomization and blinding
Prior to the study, we generated a random allocation sequence using STATA 16.0 statistical software (Stata Statistical Software, College Station, TX, USA) and subsequently incorporated it into the Research Electronic Data Capture (REDCap), an online data management system, to assign the participants to either the PENG group (0.375% ropivacaine) or the placebo group (normal saline placebo) at a 1:1 ratio, in blocks of 4. An independent pharmacist will prepare a 20 ml solution of 0.375% ropivacaine and a 20 ml solution of normal saline, while an independent research staff will unveil the randomization sequence on REDCap and select the designated study drug. This entire process is masked from all the other researchers involved in the study, including the anesthesiologists who perform the block, and the physical therapists who perform the prehabilitation and evaluate the outcomes.
Data management
All study data will be collected promptly through REDCap. The images and videos of the block will be kept on a secured computer without an internet connection. Each patient will be assigned a unique study identifier, facilitating database linkage. Protection of personal health information will be upheld, with its disclosure limited to members of the research team only as required by specific study purposes. The data will be only accessible to authorized personnel through password-protected access. Specific privilege assignments within the database will be employed to restrict data access to the minimum necessary for each individual’s role in the trial. The allocation data will be only available to the independent research staff who unveil the allocation sequence. Electronic audit trails will be implemented to automatically capture and record any changes made to database contents.
Statistical analysis
The primary outcome will be analyzed with the Fischer’s exact test. The proportion and its 95% confidence interval of the difference between the groups will be obtained.
For secondary outcomes, the analysis will be performed using the Fischer’s exact test or the Wilcoxon rank-sum test. The mean values and its 95% confidence interval, or the proportions and its 95% confidence intervals between the groups will be reported.
Baseline characteristics will be summarized as summary statistics (minimum, median, and maximum) for continuous variables and as frequency and proportion for binary variables.
All the data analysis will be performed in the intention-to-treat principle using the R software (R Core Team, Vienna, Austria).
Monitoring
The data monitoring committee (DMC) will consist of members independent from the research team. The DMC will report at defined intervals to assess progress, identify potential issues, and promptly address any concerns that may arise.
Any serious adverse events, in addition to all non-serious adverse events that are both unexpected and determined to be related to the study treatment, will be documented in the study database, and reported as mandated to the hospital’s ethics committee, which will decide if the study needs to be stopped.
Dissemination Plans
Dissemination plans include presentations at local, national, and international scientific conferences, and publications in scientific journals. The full protocol will be available with the publications. The participant-level dataset and statistical code will also be disseminated when requested.