Clinical trial NCT05498870
Conditions: ACL Injury Post Operative Pain
Keywords: acl injury acl repair
Sponsor: Medical University of South Carolina
Start date: 2022-08-25; Completion date: 2023-08-14
Enrollment: 82 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will consist of patients 12 years and older undergoing ACL reconstruction using a quadriceps or bone-patella tendon bone (BTB) graft. The patients will be randomized to adductor canal block alone, or adductor canal block + iPACK block. The primary goal will be to determine the differences in postoperative pain during the first 72 hours when comparing the two groups. Secondary outcomes will include opioid utilization during the first 72 hours postoperatively and range of motion including terminal knee extension at postoperative follow-up visits.

Detailed description:

Arms: arm 1: Participants randomized to the ACB only group will receive an adductor canal block alone. arm 2: Participants randomized to the ACB + iPACK group will receive both the ACB and iPACK block.
Interventions: intervention 1: Adductor Canal Block (ACB) Only intervention 2: Adductor Canal Block (ACB) + iPACK Block
Intervention descriptions: intervention 1: Patients will receive an ACB with lidocaine skin wheal intervention 2: Patients will receive an ACB with iPACK block

Protocol documents:
Prot_SAP_000.pdf: 
 
Functional and Analgesic Effects of The Addition of iPACK Blocks to Continuous Adductor Canal 
Blocks Following ACL Reconstruction with Quadriceps Tendon Autograft: A Randomized 
Controlled Trial 
 
NCT05498870 
 
Protocol Date: 06-17-2022 


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PROTOCOL TITLE: 
Studying the effects of iPACK blocks with adductor canal blocks for postoperative analgesia 
following ACL reconstruction 
 
PRINCIPAL INVESTIGATOR: 
• 
Carey Brewbaker, M.D. 
 
 
 


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1.0 
Objectives / Specific Aims 
We hypothesize that participants receiving the ACB-iPACK intervention will have lower 
subjective pain scores and lower total opioid consumption in the initial 72-hours of the 
postoperative window and increased range of motion at subsequent follow up visits with 
their surgeon. 
2.0 
Background 
Adequate analgesia with maintained functionality is crucial to recovery for patients 
undergoing outpatient anterior cruciate ligament (ACL) reconstruction. Perioperative 
peripheral nerve blocks have been utilized in these procedures to maximize postoperative 
pain control, minimize side effects from IV analgesics, and facilitate discharge from 
PACU. Past research has pointed to adductor canal blocks (ACBs) being superior to 
femoral nerve blocks (FNBs) for preserving motor strength during postoperative analgesia 
following knee arthroplasty [1]. Similar studies specifically looking at ACL reconstruction 
have shown similar analgesic effects between both blocks, with ACBs having a much 
higher maximal voluntary contraction of the quadriceps while in the PACU [2]. Further 
studies have found that for patients who underwent TKAs, ACBs were insufficient in 
reliving posterior knee pain due to the saphenous nerve innervating only the anterior and 
medial knee [3] [4]. This study looks to determine whether an increasingly used technique 
called iPACK block can be used to augment postoperative analgesia when used in 
conjunction with an ACB for ACL reconstruction. iPACK (infiltration between the 
popliteal artery and the capsule of the posterior knee) is thought to work by blocking 
branches of the popliteal plexus and genicular nerves, providing analgesia for the posterior 
knee that ACBs do not cover [5].  Previous studies have shown positive outcomes for TKA 
patients using an ACB-iPACK combination with regards to subjective pain measures and 
opioid consumption, however this relationship has not been confirmed for ACL 
reconstruction [6].  
3.0 
Intervention to be studied (if applicable) 
This study will consist of participants 12 years and older undergoing ACL reconstruction 
using a quadriceps or bone-patella tendon bone (BTB) graft. The primary goal will be to 
determine the differences in postoperative pain during the first 72 hours when comparing 
an ACB + iPACK block to an ACB alone. Secondary outcomes will include opioid 
utilization during the first 72 hours postoperatively and range of motion including terminal 
knee extension at postoperative follow-up visits. 
 
 
4.0 
Study Endpoints (if applicable) 
• 
The primary endpoint will measure subjective pain scores as 12-hour intervals during 
the first 72 hours of the postoperative window as collected by a study team member. 
• 
The secondary endpoints will measure total postoperative opioid consumption 
through postoperative day 2, as well as measure the range of motion and terminal 
knee extension of participants at postoperative follow-up visits.  
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 


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Participants being scheduled for an ACL reconstruction procedure who meet inclusion 
criteria will be approached and offered enrollment upon arriving to the pre-operative area 
before the procedure.  
Inclusion Criteria  
• 
Age 12 years and older 
• 
Patients who are scheduled to undergo an ACL reconstruction with quadriceps 
or BTB graft.  
Exclusion Criteria 
• 
Any contraindication to receiving regional anesthesia. This may include 
infection at the site of injection, allergy to local anesthetic, or pre-existing nerve 
injury.  
• 
Patients undergoing hamstring graft or allograft for ACL  
• 
Pre-existing infection at the site of injury 
• 
Patients on chronic opioid treatments  
• 
Pre-existing sensory or motor deficit in operative extremity 
• 
Patients having a revision of previous ACL reconstruction 
• 
Pregnant and/or lactating women  
• 
Weighs less than 40kg 
 
6.0 
Number of Subjects 
We will enroll and randomize 82 subjects.  
7.0 
Setting 
Participants will be approached about the study during their pre-surgical consultation with 
their surgeon and formal consent will be obtained while they are in pre-op/holding prior to 
the procedure, both of which will take place at MUSC’s Charleston West campus, or 
MUSC’s Rutledge Tower. The study procedure will also take place at either of these 
locations.  
8.0 
Recruitment Methods 
The study team will refer to the OR and clinic schedules available on EPIC to see which 
patients qualify. If time allows, the surgeon will introduce the study during the surgical 
consultation in clinic and provide an informational brochure about the study. If not, the 
study will be introduced to the patient in the pre-operative holding area prior to the 
procedure.   
9.0 
Consent Process 
Consent will be obtained by IRB approved study team members who have a medical 
degree and are qualified to discuss the clinical nature of the options being offered.  
• Potential study participants will be invited to participate in the study. Initial contact 
will be made with the patient on the day of the scheduled procedure by an IRB 


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approved study team member. The study will be explained, and the patient will be 
given time to read the consent thoroughly and ask any questions. This will happen 
in the private pre-op area.  
• Written informed consent will be obtained if the participant agrees to participate 
after the study is thoroughly explained. For participants under 18 years of age, 
informed consent will be obtained by their parent or legal guardian and assent will 
be obtained from the participants themselves. A copy of the signed informed 
consent will be provided to the participant. 
 
10.0 Study Design / Methods 
This study will be a prospective, single-center, single-blind randomized controlled 
trial. Participants will be randomized by using a stratified randomization technique, 
stratified by sex into two groups:  
1) continuous adductor canal block alone (ACB Only) or  
2) continuous adductor canal block with iPACK block (ACB + iPACK). 
Preoperative: Adult participants and pediatric patients >70kg will receive 1g 
Tylenol and 1-2mg midazolam and up to 20mcg of dexmedetomidine for pre-
procedure anxiolysis. Patients between 12 and 18 years old will receive Tylenol 
with a dose based on weight (Table 1), and 1-2mg midazolam and up to 20mcg of 
dexmedetomidine.  
 
 
 
 
 
 
 
 
All participants will receive the continuous adductor canal block which consists of 
20cc of 0.25% plain ropivacaine and will be given followed by placement of an 
OnQ pump infusing 0.2% ropivacaine at 6cc/hr. (4cc/hr. for participants less than 
60Kg).  
Those who are randomized to the ABC + iPACK group will receive an additional 
block consisting of 20cc of 0.25% Ropivacaine placed in the popliteal fossa 
between the popliteal artery and the posterior aspect of the capsule of the knee 
joint.  
Participants randomized to the ACB-only group will receive a skin wheal at the 
same site where the iPACK block would have been placed in an effort to maintain 
the blind.  
 
Perioperative: Participants will be appropriately sedated as per clinical care.  
Table 1. Tylenol Dosage Based on Weight for Pediatrics 
Weight 
Dosage 
≥70kg 
1,000mg 
45-70kg 
650mg 
<45kg 
500mg 


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Postoperative: Participants will be given 0.2mg hydromorphone every 8 minutes as 
needed for pain, and 5mg of oxycodone may be administered adjunctively as 
needed if pan scores remain elevated after intravenous hydromorphone  
Post-discharge: Participants will be instructed to schedule two post-operative 
follow up appointments with their surgeon as well as physical therapy. They will 
also be prescribed the following medication regimen after discharge:  
Ages 12-18 and <70kg 
• Tylenol 650mg q8h 
• Naproxen 250mg q8h 
• Oxycodone 5mg q4h PRN pain 
• Aspirin 81mg daily for DVT prophylaxis 
 
All patients ≥ 18 years of age and pediatric patients ≥70kg 
• Tylenol 1,000mg q8h 
• Naproxen 500mg twice daily 
• Oxycodone 5-10mg q4h PRN pain 
• Aspirin 325mg daily for DVT prophylaxis 
 
Additionally, participants will be instructed to follow the following bracing and 
weight bearing instructions: 
• Weight bearing as tolerated and no brace for isolated ACL reconstruction, 
small 2 or less sutures and all inside repair 
• Brace for bucketed meniscus with inside out repair, and associated mcl, OR 
large repaid (more than 3 sutures) 0-90, and weight bearing as tolerated in 
extension  
• Non-weight bearing with brace for meniscus roots, and lateral meniscus 
tears.  
Currently, there is no consensus guidelines for venous thromboembolism 
prophylaxis in the setting of anterior cruciate ligament reconstruction 
surgery.  Moreover, there is no universally agreed-upon dose for use of aspirin in 
the postoperative state for VTE prophylaxis.  There is current evidence which 
would suggest aspirin is an effective and safe medication for DVT prophylaxis and 
other major lower extremity orthopedic surgical procedures.  Additionally, current 
practice patterns would suggest that aspirin is the most commonly utilized VTE 
prophylaxis following anterior cruciate ligament reconstruction. [8] 
 
Baseline and Randomization 
After consenting and confirmation of meeting eligibility criteria, the participant will 
undergo the procedure as scheduled and as standard of care. The participant will be 


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randomized before they are anesthetized, as the block will be prepared and placed prior 
to the start of surgery.  
If randomized to ACB-Only (Group A) the participant will receive the ACB block first. 
The injection site is prepared with a sterile solution, an injection of lidocaine is given 
to numb the area, then using ultrasound guidance a needle is inserted into the adductor 
canal at the mid-thigh where a catheter is placed to administer the long-acting 
anesthetic.  Next, to maintain the blind, the participant will receive a skin wheal with 
lidocaine at the same location as Group B has the iPACK block placed. 
 
 
 
 
 
 
 
If randomized to ACB + iPACK (Group B) the participant will be administered the 
ACB first as stated above and the iPACK block second. The iPACK block will be 
placed at the posterior part of the knee. The area will be numbed first using lidocaine, 
then using ultrasound guidance, a needle will be inserted in the popliteal fossa between 
the popliteal artery and the capsule of the knee.  
 
 
 
 
 
 
 
 
 
Follow-Up 
The participant will be asked to provide their average pain score, worst pain score, and 
lowest pain score using a visual analog scale from 0-100 with 100 being the worst at 
various time points during the postoperative period. The first pain scores will be 
recorded before they leave the PACU on the day of the procedure. Beginning the 
following morning, the participant will receive a text message link sent by Twilio’s 
secure server that opens a survey housed in RedCap. The first text message will arrive 
at 9:00 AM and will follow the schedule in Table 6.   
They will receive a text message from a secure server asking the average pain 
questions as well as what medications they took for pain (including medication name, 
dosage, and frequency). The set of questions will state what time window (example: 
Table 5. Post-Op Follow Up Assessments 
Outcome Measure 
Instrument 
Collected 
Pain Rating 
Average pain, most pain, least pain from 0-10 
POD Days 0-3 
Opioid Consumption 
Number of pills taken in time period  
POD Days 0-3 
Physical Therapy 
Range of Motion and terminal knee extension  
Postoperative Visit 1 
and 2 
Adverse Events 
Adverse Events 
Throughout enrollment 
Table 4. Baseline and Intraoperative Assessments 
Demographics 
Baseline 
Pre-op meds including opioids in past 24 hours 
Randomization 
Anesthesia intra-op data 
Surgical techniques 
Adverse Events 


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12:00 AM midnight the night prior to 12:00 PM noon the same day) to consider when 
answering the questions. If the participant has been discharged from the hospital, they 
will answer these questions in the text message each day. If they are admitted to the 
hospital at this point in time, the information will be gathered from their chart for 
medications and asked verbally for pain scores. Range of motion and terminal knee 
extension will also be recorded at the in-person postoperative follow up visits.  
If the participant is unable or unwilling to receive text messages, they will be provided 
a document to record their pain and medications for the pre-determined intervals so 
when a study member contacts them, they are able to relay their answers back 
accurately.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.0 Data Management  
• 
The study will be a double-blinded randomized controlled trial of participants 
undergoing ACL reconstruction at one academic medical center.  Although the 
anesthesiologist administering the block will not be blinded, the surgeons, 
participants, and study statistician will be blinded to treatment assignment.  
Participants will be randomized to receive either ACB or ACB + iPACK block.  We 
will use stratified randomization, stratifying on biologic sex, to ensure similar 
distributions of male/female participants in each treatment arm the same. 
• 
The primary outcomes of interest are participant reported postoperative pain over 
time and quadricep strength based on the leg raise and knee extension test.  Post-
operative VAS pain score reported as average, worst, and least pain will be collected 
on post-op day 0 (after 12pm), 1 (prior to 12 pm and after 12 pm), and 2 (before 12 
pm).  The association between postoperative pain with block type will be evaluated 
using a series of linear mixed models evaluating average pain, worst pain, and least 
pain as dependent variables.  Models will include fixed effects for preoperative pain 
score, block type, postoperative time, and the interaction between block type and 
post-operative time and a random subject effect to account for correlation between 
pain scores collected on the same subject over time.  Model assumptions will be 
checked graphically, and transformations will be considered as needed.  The 
difference in patient reported pain between block type by post-operative time and 
pain score type will be evaluated using a series of linear contrasts.  A similar study 
Table 6. Post-Op Follow Up Assessment Schedule 
Post-Op Day 
Time of Text Message 
Data Collection Time Period 
POD 0 
Right before discharge 
Waking up from surgery to discharge 
POD 1-AM 
9:00 AM 
Discharge to 11:59 midnight prior 
POD 1-PM 
3:00 PM 
12:00 AM midnight night prior to 12:00 PM noon 
same day 
POD 2-AM 
9:00 AM 
12:01 PM noon day prior to 11:59 AM midnight 
night prior 
POD 2-PM 
3:00 PM 
12:00 AM midnight prior to 12:00 PM noon same 
day 
POD 3-AM 
9:00 AM 
12:01 PM noon day prior to 11:59 AM midnight 
night prior 
POD 3-PM 
3:00 PM 
12:00 AM midnight prior to 12:00 PM noon same 
day 


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by Amer (2018)1 comparing combined Adductor Canal and iPACK Blocks versus 
combined Adductor Canal and Periarticular Injection blocks for pain management in 
ACL Reconstruction Surgery found a difference in VAS pain scores of 1.5 between 0 
to 8 hours post-op and standard deviation in VAS pain of 2.5 units.  A sample size of 
n = 35 participants per treatment arm (70 total) with at least 3 measures of pain 
provides 80% power to detect a difference in pain score of 2 units at significance 
level α = 0.004 (Bonferroni corrected for 4 comparisons) and assuming a compound 
symmetric covariance structure with a conservative standard deviation = 3.0 and 
correlation within subject is ρ = 0.33.  We will enroll 41 participants (82 total) in 
each arm to allow for up to 20% attrition. 
• 
Secondary outcomes include cumulative post-operative opiate consumption over time 
(POD 0 pm, 1 am/pm, and 2 am), and difference in range of motion between surgical 
and non-surgical leg at first clinic visit (7-21 days post-op) and 6 weeks PO. 
Associations between these secondary outcomes with block type will be evaluated 
using a linear mixed approach.  Similar to the primary outcome, models will include 
fixed effects for type, time, and the interaction between block type and time.  The 
model for cumulative opiate consumption will also include a fixed effect for intra-
operative opiates received and the model for range of motion will include a fixed 
effect for pre-operative difference in range of motion between surgical and non-
surgical leg. 
• 
All data will be kept on a password protected MUSC server and in a REDCap 
database. All paper data sheets will be kept in a locked cabinet, in a locked office that 
only IRB approved study team members have access to. Participants will be given a 
study ID number that will be used to identify them throughout the study.  
12.0 Data Safety Monitoring 
• 
The study will be reviewed annually by the Department of Anesthesia’s DSMB.   Minutes and 
outcomes from these meetings will be reported to the IRB as required. 
 
• 
Information regarding Adverse Events is to be obtained and documented by the surgery center 
anesthesia attending and/or the study team member performing the data collection by 
questioning or examining the subject. All new complaints and symptoms (i.e., those not 
existing prior to signing of informed consent) will be recorded on the AE CRF. All AEs will 
be characterized in terms of their start and stop dates, start and stop times, intensity, action 
taken, relationship to research study, subject outcome and whether or not the AE led to an 
SAE. 
 
• 
Adverse events will be recorded and reported to the Department of Anesthesia’s Data Safety 
Monitoring Board and the IRB per policy. 
 
• 
PHI will be managed in a manner that complies with institutional rules and regulations.  
There will be an enrollment log that links the study ID number to the participant.  This log 
will be kept on a MUSC password protected server that can only be accessed by IRB 
approved study personnel.  
 
 
13.0 Withdrawal of Subjects  


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• 
The participant has the right to voluntarily withdraw consent from the study at any 
time for any reason without prejudice to his/her future medical care by the physician 
or at the institution. For the occasional participant who withdraws consent, the date 
and reason for consent withdrawal should be documented. Participant data will be 
included in the analysis up to the date of the consent withdrawal. 
• 
Investigators may stop a subject’s participation in the study at any time if they decide 
it is in the subject’s best interest. They may also do this if the subject does not follow 
the investigator’s instructions.  
 
14.0 Risks to Subjects 
• 
If a subject chooses not to participate the risk is the same since the interventions 
used are both standard of care at MUSC and will be offered regardless of study 
population.  
• 
The interventions for both blocks include risks such as bleeding, infection, nerve 
damage, local anesthetic toxicity, allergic reaction, and/or damage to surrounding 
structures. These risks are rare.  
• 
Subjects will be randomly assigned to receive either the adductor canal block, or 
adductor canal block with iPACK block. One group may prove to be less beneficial 
than the other. 
• 
There is a risk of loss of confidentiality.  
 
15.0 Potential Benefits to Subjects or Others 
There is a potential benefit that the subject’s participation in the study may 
contribute to knowledge in this area of practice and may impact subject care in the 
future. The subject could also experience less post-operative pain.  
 
16.0 Sharing of Results with Subjects 
• 
Results will not be shared with participants or their families. 
 
17.0 Drugs or Devices (if applicable)  
• 
The drugs (all FDA approved for ACB blocks and iPACK blocks) used for both 
blocks will be prepared by the OR pharmacy under a sterile hood.  
• 
The contents of the injectate will be based off of the participant’s randomly assigned 
group.  
• 
The pharmacist will not be blinded to the randomization.  
• 
All drugs are FDA approved for use in adults and standard of care off label in 
children according to ASRA/ESRA guidelines[7]. 
References 


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1. 
R. Johnson, S. Kop, J. Hebl, P. Erwin and C. Mantilla, "Falls and major orthopaedic 
surgery with peripheral nerve blockade: a systematic review and meta-analysis.," Br J 
Anaesth, vol. 110, pp. 518-528, 2013.  
2. 
R. Brull, "Adductor Canal Block Provides Noninferior Analgesia and Superior Quadriceps 
Strength Compared with Femoral Nerve Block in Anterior Cruciate Ligament 
Reconstruction," Anesthesiology, vol. 124, no. 5, pp. 1053-1064, 2016.  
3. 
K. H. Andersen, "Local infiltration analgesia in joint replacement: the evidence and 
recommendations for clinical practice," Acta Anaesthesiol Scand, vol. 55, pp. 778-784, 
2011.  
4. 
F. Abdallah, C. Madjdpour and R. Brull, "Is sciatic nerve block advantageous when 
combined with femoral nerve block for postoperative analgesia following total knee 
arthroplasty?," Can J Anaesth, vol. 63, pp. 552-568, 2016.  
5. 
J. Tran, L. Arango, P. Peng, S. Sinha, A. Agur and V. Chan, "Evaluation of the iPACK 
block injectate spread: a cadaveric study.," Reg Anesth Pain Med, vol. 208, p. 100355, 
2019.  
6. 
T. Et, "Comparison of iPACK and periarticular block with adductor block alone after total 
knee arthroplasty: a randomized clinical trial," Journal of Anesthesia, 2022. 
  
7. 
Suresh S, Ecoffey C, Bosenberg A, Lonnqvist PA, de Oliveira GS Jr, de Leon Casasola O, 
de Andrés J, Ivani G. The European Society of Regional Anaesthesia and Pain 
Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations 
on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Reg Anesth 
Pain Med. 2018 Feb;43(2):211-216. 
8. 
Keller RA, Moutzouros V, Dines JS, Bush-Joseph CA, Limpisvasti O. Deep Venous 
Thrombosis Prophylaxis in Anterior Cruciate Ligament Reconstructive Surgery: What Is 
the Current State of Practice? Sports Health. 2018 Mar/Apr;10(2):156-159. doi: 
10.1177/1941738117730576. Epub 2017 Sep 19. PMID: 28927346; PMCID: 
PMC5857726.