Comparison Between the Ultrasound Guided Pericapsular Nerve Group Block and Anterior Quadratus Lumborum Block in Elderly Patients Undergoing Total Hip Replacement Surgeries: A Randomized Controlled Clinical Trial
Phase: PHASE4
Conditions: Post Operative Analgesia
Sponsor: Cairo University

Study Protocol and Statistical Analysis Plan 
Version: 1.0 
Date: 16 March 2022 
Official Title: 
Comparison between the Ultrasound-Guided Pericapsular Nerve Group Block and 
Anterior Quadratus Lumborum Block in Elderly Patients Undergoing Total Hip 
Arthroplasty: A Randomized Controlled Clinical Trial 
ClinicalTrials.gov Identifier: NCT06679764 
Sponsor / Responsible Party: 
Department of Anesthesia, Surgical Intensive Care and Pain Management, Faculty of 
Medicine, Cairo University, Cairo, Egypt 
Principal Investigator: Mohamed A. Ollaek, MD 
Co-Investigators: Ahmed Elshall, MD; Osama Asaad, MD; Bassant M. Abdelhamid, 
MD; Alaa F. Abd Elbadei, MD 
 
Study Start Date (Actual): 1 May 2022 
Primary Completion Date (Actual): 15 September 2023 
Study Completion Date (Actual): 31 January 2024 

1. Background and Rationale 
Total hip arthroplasty (THA) is widely performed for traumatic hip fractures and 
degenerative hip disease in older adults and is associated with substantial postoperative 
pain that can delay mobilization and prolong hospital stay. Effective multimodal 
analgesia is essential to facilitate early rehabilitation and reduce opioid-related adverse 
effects in this vulnerable population. 
Opioid analgesics provide rapid pain relief but carry important risks in elderly patients, 
including respiratory depression, delirium, constipation, nausea/vomiting, and prolonged 
hospitalization. Regional anesthesia techniques, particularly peripheral nerve and fascial 
plane blocks, are increasingly used as opioid-sparing strategies after THA. 
The pericapsular nerve group (PENG) block targets the articular branches of the femoral, 
obturator, and accessory obturator nerves supplying the anterior hip capsule via local 
anesthetic injection between the psoas tendon and superior pubic ramus. It has been 
described as providing effective, largely motor-sparing postoperative analgesia for hip 
surgery and acute pain after hip fracture. 
The anterior quadratus lumborum block (AQLB) deposits local anesthetic in the fascial 
plane between the quadratus lumborum and psoas major muscles, aiming to block lumbar 
plexus articular branches and provide analgesia for hip surgery. Previous studies reported 
favorable analgesic profiles of AQLB in THA. 
Both PENG and AQLB appear anatomically capable of covering the operative field in 
THA, but they may differ in their balance between analgesic efficacy, opioid-sparing 
effect, and motor impairment. Comparative data between these two techniques in elderly 

patients undergoing THA under general anesthesia are limited. This trial evaluates 
whether ultrasound-guided PENG block or AQLB offers superior postoperative analgesia 
and functional recovery compared with standard opioid-based analgesia and compares 
PENG and AQLB directly. 
2. Study Objectives 
2.1 Primary Objective 
To compare total intravenous morphine consumption in the first 24 hours after surgery 
among three groups of elderly patients undergoing unilateral THA under general 
anesthesia: PENG block group, AQLB group, and Control group (opioid analgesia only). 
2.2 Secondary Objectives 
To compare intraoperative fentanyl consumption between the three groups. 
To compare time to first rescue analgesia postoperatively. 
To compare Numeric Pain Rating Scale (NRS) scores at rest and during passive 90° hip 
flexion at predefined postoperative time points (30 min, 2, 4, 6, 8, 12, 18, and 24 hours). 
To assess block failure rate, defined as the requirement for more than one rescue 
morphine dose in the first postoperative hour. 
To compare motor recovery (manual muscle test for quadriceps and iliopsoas, and active 
hip flexion range of motion) over the first 24 hours. 
To compare time to first ambulation and length of hospital stay. 

To compare intraoperative hemodynamic profiles (heart rate and mean arterial pressure). 
To compare the incidence of block-related complications and morphine-related adverse 
events (e.g., nausea/vomiting, respiratory depression, hypotension, falls). 
To compare block performance time and surgical duration between groups. 
3. Study Design 
This is a prospective, randomized, double-blind, parallel-group clinical trial with three 
arms (PENG, AQLB, and Control) with equal allocation (1:1:1). The study is conducted 
at a single tertiary university hospital (Orthopedic Surgical Theater, Cairo University 
Hospital). Patients and outcome assessors are blinded to group assignment; the 
anesthesiologist performing the block is not involved in postoperative assessments. 
4. Study Population 
4.1 Inclusion Criteria 
Age ≥65 years. 
Male or female patients with traumatic hip fracture scheduled for elective unilateral THA 
via an anterolateral approach. 
Planned anesthesia: general anesthesia. 
Body mass index (BMI) 20–35 kg/m². 
American Society of Anesthesiologists (ASA) physical status I–III. 
Provision of written informed consent. 

4.2 Exclusion Criteria 
Known allergy or contraindication to local anesthetics (bupivacaine) or opioids. 
History of psychological disorders and/or chronic pain requiring long-term analgesic 
therapy. 
Pre-existing peripheral neuropathy affecting lower limbs. 
Coagulopathy or current anticoagulant therapy precluding regional blocks. 
Unstable or severe cardiac disease (e.g., unstable coronary syndromes). 
Acute respiratory disease (e.g., active chest infection, respiratory failure). 
Advanced liver disease (liver enzymes >3× upper limit of normal). 
Severe renal impairment (serum creatinine >2 mg/dL). 
Local infection at the intended needle puncture site. 
Expected operative duration >3 hours. 
Refusal to participate. 
4.3 Withdrawal Criteria 
Withdrawal of consent at any time. 
Intraoperative events requiring deviation from protocol (e.g., conversion to different 
surgical procedure). 

Significant protocol violations deemed to invalidate study data (to be documented and 
evaluated case by case). 
5. Ethical and Regulatory Considerations 
The study was approved by the Research Ethics Committee, Faculty of Medicine, Cairo 
University (ID: MD-16-2022, approval date 16 March 2022). The trial is registered at 
ClinicalTrials.gov (NCT06679764). All participants (or their legal representatives) 
receive detailed verbal and written information about the study and sign a written 
informed consent form prior to any study procedure. Data confidentiality is maintained 
according to institutional and national regulations. Participant identities are coded and not 
included in reports or publications. 
6. Interventions 
All patients undergo standardized general anesthesia and perioperative management as 
detailed below. 
6.1 General Anesthesia Regimen 
Monitoring includes ECG, non-invasive blood pressure, pulse oximetry, and end-tidal 
CO₂. Induction is achieved with fentanyl 2 μg/kg IV, propofol 2 mg/kg IV, and 
atracurium 0.5 mg/kg IV to facilitate tracheal intubation. Anesthesia is maintained with 
isoflurane 1–1.5% in an oxygen-air mixture (FiO₂ 0.5) and atracurium 0.1 mg/kg IV 
every 30 minutes. Ventilation is adjusted to maintain end-tidal CO₂ between 30–35 
mmHg. Hypotension is treated with crystalloids (0.9% saline and/or Ringer’s acetate) and 
incremental ephedrine 5 mg doses as needed. At the end of surgery, neuromuscular 

blockade is reversed with neostigmine 0.05 mg/kg and atropine 0.02 mg/kg IV and 
patients are extubated after full recovery. 
6.2 Study Arms 
6.2.1 PENG Block Group 
After induction of general anesthesia and before surgical incision, patients in the PENG 
group are placed supine. A low-frequency curvilinear ultrasound probe (2–5 MHz) is 
positioned transversely over the anterior inferior iliac spine and rotated approximately 
45° counter-clockwise along the pubic ramus. Key sonoanatomy includes the iliopubic 
eminence, iliopsoas muscle/tendon, and femoral nerve and vessels. A 22-G, 50 mm nerve 
block needle is inserted in-plane from lateral to medial to reach the fascial plane between 
the iliopsoas fascia and the pubic ramus, under the iliopsoas tendon. After negative 
aspiration and a 1 mL saline test injection, 30 mL of local anesthetic mixture (29 mL 
0.25% bupivacaine plus 1 mL containing 4 mg dexamethasone) is injected with 
visualization of appropriate spread. 
6.2.2 Anterior Quadratus Lumborum Block (AQLB) Group 
After induction of general anesthesia, patients assigned to the AQLB group are 
positioned in the lateral decubitus position with the operative side up. A low-frequency 
curvilinear ultrasound probe is placed horizontally above the iliac crest to visualize the 
transverse process, psoas major, erector spinae, and quadratus lumborum muscles. A 22-
G, 50 mm needle is advanced in-plane from posterior to anterior into the fascial plane 
between quadratus lumborum and psoas major. Following hydro-localization with 1 mL 

saline, 30 mL of 0.25% bupivacaine with 4 mg dexamethasone (29 mL + 1 mL) is 
injected in this plane. 
6.2.3 Control Group 
Patients in the Control group do not receive a regional nerve or fascial plane block. 
Analgesia is based on systemic opioids only: intraoperative fentanyl and postoperative 
morphine as described below. A sham dressing may be applied to mimic a block site and 
maintain blinding. 
6.3 Intraoperative Analgesia and Monitoring 
Rescue analgesia consists of fentanyl 1 μg/kg IV if mean arterial pressure or heart rate 
increases more than 20% above baseline values. Hemodynamic variables (heart rate and 
mean arterial pressure) are recorded at baseline, 5 minutes after intubation, at skin 
incision, and then at regular intervals throughout surgery. 
6.4 Postoperative Management 
In the post-anesthesia care unit (PACU), patients are monitored for 2 hours. NRS scores 
at rest and during movement, mean arterial pressure, and heart rate are recorded on 
arrival. On the ward, patients receive paracetamol 500 mg IV every 6 hours. Rescue 
analgesia consists of morphine 0.05 mg/kg IV bolus when NRS ≥4 at rest or during 
movement, with a maximum dose of 0.3 mg/kg in 24 hours. Ondansetron 0.1 mg/kg IV is 
administered for moderate or severe postoperative nausea/vomiting. 
6.5 Definition of Time to First Ambulation and Hospital Discharge 

Time to first walk is defined as the interval between the end of surgery and the time at 
which the patient can take at least three steps with a walker under physiotherapist 
supervision. Length of hospital stay is defined as the number of days from surgery until 
hospital discharge as decided by the orthopedic surgeon. 
7. Outcomes and Assessments 
7.1 Primary Outcome 
The primary outcome is total morphine consumption (mg) in the first 24 postoperative 
hours, calculated as the cumulative dose of intravenous morphine administered in the 
PACU and on the ward up to 24 hours after surgery. 
7.2 Secondary Outcomes 
To compare intraoperative fentanyl consumption between the three groups. 
To compare time to first rescue analgesia postoperatively. 
To compare Numeric Pain Rating Scale (NRS) scores at rest and during passive 90° hip 
flexion at predefined postoperative time points (30 min, 2, 4, 6, 8, 12, 18, and 24 hours). 
To assess block failure rate, defined as the requirement for more than one rescue 
morphine dose in the first postoperative hour. 
To compare motor recovery (manual muscle test for quadriceps and iliopsoas, and active 
hip flexion range of motion) over the first 24 hours. 
To compare time to first ambulation and length of hospital stay. 

To compare intraoperative hemodynamic profiles (heart rate and mean arterial pressure). 
To compare the incidence of block-related complications and morphine-related adverse 
events (e.g., nausea/vomiting, respiratory depression, hypotension, falls). 
To compare block performance time and surgical duration between groups. 
8. Sample Size Determination 
The planned analysis for the primary outcome is a three-arm comparison of 24-hour 
opioid consumption. Based on retrospective data reporting 24-hour hydromorphone 
consumption of 4.5 ± 2.9 mg after PENG block, a conservative standardized effect size of 
0.35 was assumed. With α = 0.05 (two-tailed), power of 80%, and three groups, the 
required sample size was 81 patients. Allowing for approximately 15% attrition, the final 
target sample size was 93 participants (31 per group). 
9. Randomization, Allocation Concealment, and Blinding 
Randomization is based on a computer-generated sequence allocating patients to the three 
study groups in a 1:1:1 ratio. Allocation concealment is achieved using serially 
numbered, opaque, sealed envelopes prepared by a study coordinator not involved in 
patient care. Envelopes are opened only after induction of anesthesia. The 
anesthesiologist performing the block opens the envelope, prepares and administers the 
assigned intervention, and has no role in postoperative assessment. Patients, surgeons, 
ward staff, and outcome assessors are blinded to group assignment. Unblinding is 
permitted only if necessary for urgent clinical management, and the reason and timing are 
documented. 

10. Data Collection and Management 
Data are recorded on pre-designed case report forms by trained staff. Source documents 
include anesthesia charts, PACU and ward observation charts, medication administration 
records, and physiotherapy notes. Data are entered into a password-protected electronic 
database with double-entry verification. Only authorized investigators have access to the 
final dataset, which is stored in de-identified form for at least five years after study 
completion. 
11. Statistical Analysis Plan 
11.1 General Principles 
Statistical analyses will be performed using IBM SPSS Statistics (version 28). All 
randomized participants who receive the allocated intervention and have outcome data 
will be included in the primary analysis (modified intention-to-treat). Two-sided tests will 
be used with a significance level of P < 0.05. Continuous variables will be assessed for 
normality using the Shapiro–Wilk test and visual inspection of histograms and Q-Q plots. 
Normally distributed variables will be presented as mean ± standard deviation and non-
normally distributed variables as median (interquartile range). Categorical variables will 
be presented as counts and percentages. Adjustment for multiple pairwise comparisons 
will use Bonferroni correction where applicable. 
11.2 Analysis Populations 
The Full Analysis Set (FAS) includes all randomized participants who receive the 
allocated intervention and provide at least one primary outcome measurement. The Per-

Protocol Set (PPS) includes participants without major protocol deviations that could 
influence the primary outcome. The primary analysis will be performed on the FAS; 
sensitivity analyses may be repeated on the PPS if protocol deviations occur. 
11.3 Handling of Missing Data 
The study is expected to have minimal missing data due to the short follow-up period. If 
missing data occur, the primary approach will be complete-case analysis. Reasons for 
missingness will be documented. No formal imputation strategy is planned. 
11.4 Baseline Characteristics 
Baseline variables (age, sex, BMI, ASA class, and other demographic or clinical 
characteristics) will be summarized by group. Continuous baseline variables will be 
compared using one-way ANOVA for normally distributed data or Kruskal–Wallis test 
otherwise. Categorical variables will be compared using chi-square test or Fisher’s exact 
test when expected cell counts are less than five. Baseline comparisons will be interpreted 
descriptively. 
11.5 Primary Outcome Analysis 
The primary outcome, total morphine consumption in the first 24 postoperative hours, 
will initially be assessed for normality. If the distribution is non-normal, the primary 
analysis will use the Kruskal–Wallis test to compare the three groups. If the overall test is 
significant (P < 0.05), pairwise comparisons between groups (PENG vs AQLB, PENG vs 
Control, AQLB vs Control) will be conducted using Mann–Whitney U tests with 

Bonferroni-adjusted significance thresholds. Median differences and 95% confidence 
intervals will be reported when appropriate. 
11.6 Secondary Outcome Analyses 
Total intraoperative fentanyl dose and other continuous secondary outcomes (such as 
time to first rescue morphine, time to ambulation, length of hospital stay, block 
performance time, and surgical duration) will be analyzed using one-way ANOVA for 
normally distributed data or Kruskal–Wallis test for skewed data, with appropriate 
pairwise post-hoc tests. NRS pain scores at rest and during movement and motor 
recovery scores will be analyzed at each time point using Kruskal–Wallis tests with 
Bonferroni-adjusted Mann–Whitney comparisons. Exploratory repeated-measures 
analyses (e.g., mixed-effects models) may be used to evaluate time-by-group interactions 
when assumptions are satisfied. Categorical outcomes, such as adverse event incidence 
and block failure rates, will be compared using chi-square or Fisher’s exact tests as 
appropriate. 
11.7 Subgroup and Sensitivity Analyses 
No formal subgroup analyses are pre-specified. Exploratory analyses may examine 
outcomes by sex, ASA class, or age category (e.g., 65–74 vs ≥75 years), clearly labeled 
as post-hoc. Sensitivity analyses may be performed excluding protocol deviations or 
extreme outliers in morphine consumption to evaluate the robustness of the primary 
findings. 
11.8 Interim Analyses and Stopping Rules 

No interim efficacy or futility analyses were planned or conducted. The study is small, 
single-center, and short-term, and no formal stopping rules beyond standard clinical 
safety judgment were defined. 
12. Safety Monitoring 
All serious adverse events and suspected block-related complications will be recorded 
from block performance until 24 hours postoperatively and throughout the hospital stay. 
Any severe or unexpected serious adverse event judged related to the intervention will be 
reported to the institutional ethics committee according to local regulations. Given the 
limited size and low risk of the study, no independent data monitoring committee is 
established; safety monitoring responsibilities lie with the principal investigator and the 
department head. 
13. Dissemination Plan 
Study results will be reported on ClinicalTrials.gov and submitted for publication in peer-
reviewed journals in anesthesia and orthopedics. Authorship will follow the criteria of the 
International Committee of Medical Journal Editors. Participants will not be individually 
identified in any report or publication.