Clinical trial NCT03818919
Conditions: Rotator Cuff Tear
Sponsor: Henry Ford Health System
Start date: 2019-01-22; Completion date: 2020-12-31
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, single blinded, standard of care controlled clinical trial. This project aims to compare postoperative pain control in patients in two treatment arms of rotator cuff repair: a treatment group given a nonopioid pain control regimen, and a standard of care control group given standard opioid pain control regimen

Detailed description:
Study Design: This is a randomized, single blinded, standard of care-controlled clinical trial. All adult patients over eighteen desiring rotator cuff repair will be eligible. Nonnarcotic postoperative pain control regimen described below were chosen based on previous studies in fracture care and joint arthroplasty.

Patients will be consented and recruited. Once participation has been determined and consent obtained, the names of participating patients will be provided to the research pharmacy. Patients will be randomized with a computer-generated table in 2 patient blocks by the research pharmacy. Patients postoperative analgesia will be divided into one of the following 2 treatment arms: 1) A novel nonopioid pain protocol or 2) traditional narcotic pain analgesia

Primary endpoints is reduction in pain as measured by visual analogue scale and Patient-Reported Outcomes Measurement Information System. The endpoints will be collected at each post-operative day using a journal. Moreover, endpoints will be collected at the patient's first post-operative appointment. These appointments are scheduled within one-week of the index procedure.

Statistical Analysis: All continuous data will be analyzed using independent 2-group t tests and reported as means ± standard deviations. Categorical data will be compared between the 2 groups using chi-square tests and reported as counts and percentages. A preliminary test to confirm the quality of variances will be conducted prior to utilizing the t test to confirm the appropriate statistical analysis. Nonparametric equivalents Wilcoxon rank-sum and Fisher exact tests will be used as needed for nonnormal distributions and low variable numbers, respectively. A multivariable regression analysis was performed to assess for potential confounding demographic variables.

Arms: arm 1: Patients in this group will be administered a novel multimodal pain protocol post-operatively consisting of: Celecoxib, Ketorolac, Gabapentin, Acetaminophen, Diazepam arm 2: Patients will be administered a traditional post-operative pain protocol consisting of: Hydrocodone-Acetaminophen Cap 5-500
Interventions: intervention 1: Celecoxib intervention 2: Ketorolac intervention 3: Gabapentin intervention 4: Acetaminophen intervention 5: Diazepam intervention 6: Hydrocodone-Acetaminophen
Intervention descriptions: intervention 1: Post-Operative Non Opioid Pain Protocol intervention 2: Post-Operative Non Opioid Pain Protocol intervention 3: Post-Operative Non Opioid Pain Protocol intervention 4: Post-Operative Non Opioid Pain Protocol intervention 5: Post-Operative Non Opioid Pain Protocol intervention 6: Traditionally used narcotic pain protocol

Protocol documents:
Prot_SAP_001.pdf: 
Multimodal Nonopioid Pain Protocol Provides Better or Equivalent Pain Control Compared to 
Opioid Analgesia Following Arthroscopic Rotator Cuff Surgery: A Prospective Randomized 
Controlled Trial 
 
Study Protocol: 
This study was a prospective observer-blinded randomized controlled trial with 2-week follow-
up and was developed in accordance with the CONSORT (Consolidated Standards of Reporting 
Trials) statement.  This investigation received institutional re- view board approval at our 
institution (IRB no. 12316) and was registered at ClinicalTrials.gov (NCT03818919). A 
hypothesis was formulated prior to trial initiation. Between August 2019 and December 2020, 70 
consecutive patients who presented to two fellowship-trained sports surgeons and were 
scheduled to undergo a primary arthroscopic rotator cuff repair were screened for inclusion. 
Inclusion criteria required patients to be between the ages of 18 and 75 and scheduled for a 
primary arthroscopic RCR. Exclusion criteria included being non-English speaking, history of 
ipsilateral surgery in the previous year, undergoing revision surgery, use of blood thinner 
medication, his- tory of peptic ulcer disease, history of substance abuse, and intolerance or 
allergies to study medication.  
Following the surgical consult, patients consented to participate in the study. Using an adaptive 
randomization software (MD Anderson Cancer Center, Houston, TX) with a 1:1 allocation, 
patients were randomized into the opioid or nonopioid cohort. A secure computer database was 
used to store all deidentified patient data. One week prior to the date of surgery, the project 
coordinator used a secure e-mail to inform the surgical staff of the patient’s group designation. 
Because of the fact that all outcomes would be self-reported by the patient, it was not necessary 
for the treating physician to be blinded. The research coordinator was not involved in patient care 
and performed patient enrollment and data collection.  
Intervention  
All patients indeterminate of treatment group received the following medication preoperatively: 
celecoxib 400 mg, acetaminophen 975 mg, tramadol 50 mg, gabapentin 300 mg, and 8 mg 
dexamethasone intravenously. Arthroscopic RCR was performed under preoperative block. 
Intraoperatively, all patients received a local infiltration of 30 mg (1 mL) ketorolac, 1 mg (1 mL) 
epinephrine, and 150 mg (30 mL) of .5% ropivacaine. Using a 20-mL syringe and 22-gauge 
needle, local infiltrate was administered in 2-mL increments in the subcutaneous tissue around 
the portal sites.  
Patients who randomized into the control group were prescribed 40 pills of 5 mg oxycodone. 
Patients were instructed to take 1-2 pills every 4-6 hours as needed (PRN) and told not to 
supplement their analgesia with ibuprofen or acetaminophen.  
Patients in the nonopioid group received a multi- modal nonopioid analgesic regimen previously 
described in the literature. The protocol was developed to target various postoperative pain 
generators. Gabapentin was used to target neuropathic pain. Methocarbamol was selected 
12/31/2020


because of its excellent control of muscle spasms and cramps. Acetaminophen and NSAIDs 
(ketorolac and meloxicam) were used to target the pain cascade and the inflammatory process. 
Prior to discharge patients were instructed to call the on-call physician regarding uncontrolled 
pain or adverse drug events postoperatively. Patients were provided an educational pamphlet 
describing the effects of narcotics, providing ways to manage pain, and treatment goals after 
surgery. All patients were discharged home the same day of surgery.  
Outcomes  
The data collection was performed by blinded observers. Preoperatively, patients completed the 
Patient- Reported Outcomes Measurement and Information System Pain Interference Short Form 
(PROMIS PI-SF) questionnaire. Postoperatively, a mobile messaging- based outcomes collection 
software (Mosio, Inc, Seattle, WA) was used to collect patient-reported outcomes. Patients’ 
responses were submitted as numerical response via text message. This process allowed for the 
timely collection of data. Surveys were distributed to patients 3 times daily for 10 postoperative 
days.  
Patient-reported pain scores were collected using a 11-point visual analog scale 3 times a day; in 
the morning (9 AM), afternoon (1 PM), and evening (7 PM). Questions regarding adverse drug 
effects and the number of opioids consumed in the last 24-hour period (if applicable) were 
distributed each evening. Responses regarding the amount of opioid consumption daily was 
converted to morphine milligram equivalents (MME). During the first postoperative clinic visit 
(Postoperative days 7-10), patients completed the PROMIS-PI SF questionnaires.  
Information regarding the patients’ demographic data (age, body mass index [BMI], race), 
anxiety/depression status, workers compensation, and previous opioid use was extracted from the 
electronic medical record.  
Statistical Plan:  
A power analysis was performed prior to the initiation of this investigation. Following a primary 
arthroscopic rotator cuff repair, previous literature has indicated that the minimal clinically 
significant difference (MCID) in VAS pain scores is 2.4 mm on a 10-mm scale. Additionally, a 
previous case series demonstrated that the standard of deviation among VAS pain scores in 
patients following an arthroscopic rotator cuff repair was 2.3 mm on a 10-point scale. With a 
power of 80% (b level 1⁄4 .80, a level 1⁄4 .05), effect size of 2.4 mm, and standard deviation of 
2.3 mm; the minimum number of patients was 16 per cohort (n 1⁄4 32) to evaluate the primary 
outcome.  
Continuous variables are reported as means and standard deviations, while frequency counts and 
per- centages are displayed for categorical variables. Com- parisons between the two pain control 
groups (traditional and nonopioid) are performed using chi- square tests, while Fisher’s exact test 
is used when expected cell counts are <5. For continuous variables, two-group comparisons are 
performed using independent 2-sample t-tests if the variable is normally distributed and using 
Wilcoxon rank sum tests if the variable is non-normally distributed.  


Pearson correlation coefficients and their corresponding P values are provided to show the 
correlation between select variables for the traditional pain control group, the nonopioid pain 
control group, and all patients.  
Repeated-measures analyses of variance were performed using mixed models and included the 
effects of time, pain control group, and the interaction between time and pain control group as 
applicable. If needed, significant interaction effects were analyzed with post hoc comparisons 
using a Tukey-Kramer P value correction. Predicted means of the outcome variables resulting 
from the models were plotted. Statistical significance is set at P < .05 for group comparisons and 
main effect testing. Significance is set at P < .10 for interaction testing. All analyses are 
performed using SAS 9.4 (SAS Institute, Inc., Cary, NC).  
 
Results: 
Thirty patients declined to participate or were excluded, and 40 patients were included in the final 
analysis. A total of 23 patients were in the traditional group, and 17 patients were in the 
nonopioid group. Control patients on opioid pain management reported a significantly higher 
VAS pain score on postoperative day 1 (opioid: 5.7 ± 2, nonopioid: 3.7 ± 2.2; P = .011) and 
postoperative day 4 (opioid: 4.4 ± 2.7, nonopioid: 2.4 ± 2.2; P = .023). No significant difference 
was seen on any other postoperative day. When mixed measured models were used to control 
for confounding factors, the nonopioid group demonstrated significantly lower VAS and 
PROMIS-PI scores (P < .01) at every time point. Patients in the traditional analgesia group 
reported significantly more days with constipation (P = .003) and days with upset stomach (P 
= .020) than those in the nonopioid group.