Clinical trial NCT02967172
Conditions: Pain, Postoperative Ankle Fractures
Sponsor: University of Iowa
Start date: 2016-10-01; Completion date: 2018-09-21
Enrollment: 100 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the efficacy and safety of a peri-articular multimodal injection for post-operative pain control following operative management of closed, rotational ankle fractures. Enrolled subjects will be randomized to either receive or not receive intra-operative injections in addition to standard opioid analgesic regimens. Patients will be treated with standard of care surgical techniques by the treating orthopaedic surgeon for the patient's specific fracture pattern. The patients randomized into the injection cohort will receive a 25cc intra-operative injection with 200 mg ropivacaine, 0.6 mg epinephrine, 5 mg and morphine into the local superficial and deep peri-incisional tissues while under general anesthesia. Total post-operative opioid consumption expressed in morphine equivalent dose will be recorded, including IV and oral opioids. Time in hours from operation conclusion to discharge and discharge disposition (to where the patient is discharged) will also be recorded. Post-operative pain scores will be assessed and recorded in the immediate post-operative period and every 4 hours subsequently until the patient is discharged. Medication related side effects will be monitored. The investigators hypothesize that the injection cohort will have reduced pain scores, lower narcotic requirements, shorter length of stay, and be more likely to discharge to home following surgery.

Detailed description:
Periarticular fractures (bone breaks extending into the joint surface) treated by orthopaedic surgeons are associated with significant pain in the post-operative period, often requiring high doses of opioid analgesics. In recent years, the high risk of misuse, abuse, and death associated with prescription opioid use has become increasingly evident.

Although physicians are being advised to avoid administration of opioid prescriptions, alternative pain management options are limited. Currently, there is a need to investigate different pain management models in order to provide safe and effective pain relief during the post-operative period. The investigators aim to evaluate the effectiveness of peri-incisional multimodal injections as an alternative post-operative pain control method in orthopaedic trauma patients with operative ankle fractures. Approximately 200 patients will be randomized to either receive or not receive intra-operative injections in addition to standard opioid analgesic regimens. Post-operative pain management outcomes will be assessed and compared between the 2 study groups to determine effectiveness of the injections. The proposed study will build upon related work to advance post-operative pain control regimens in orthopaedic surgery. Goals include the reduction of unnecessary patient suffering, reliance on opioids, and length of stay, while improving patient experience. These aims will be accomplished through the expansion of currently used multimodal periarticular injections from populations undergoing elective surgery to orthopaedic trauma patients with rotational ankle fractures.

The study design is a prospective, double-blinded, randomized controlled trial. Patients included in the study will be randomly assigned to one of two treatment groups: intra-operative multimodal periarticular injection or control (no injection). The peri-incisional injection will consist of ropivacaine, epinephrine, and morphine. All pharmacologic agents in the anesthetic cocktail are FDA approved and have been previously used in combination during other types of orthopaedic surgeries.

All patients included in the study will receive standard post-operative opioid analgesic regimens, administered 'per needed', regardless of their assigned treatment group per study protocol. ≥ 40 patients will be randomly assigned to each group. The patients enrolled in the investigation as well as health care professionals performing post-operative assessments and collecting data will be blinded to treatment allocation. The feasibility of multimodal peri-incisional injections is supported by their current efficacy in populations undergoing elective orthopedic surgeries. These injections may be equally effective at reducing pain compared to regional anesthesia with continuous infusions, and single-shot nerve blocks.

The investigators hypothesize that the injection cohort will have reduced pain scores, lower narcotic requirements, shorter length of stay, and be more likely to discharge to home following surgery.

Arms: arm 1: A single, 25 cc multimodal analgesic cocktail will be injected following completion of ankle fracture fixation/instrumentation while the patient remains under general anesthesia and prior to skin closure. The injection will be administered as such:

* 20 mL injected into the peri-incisional soft tissues in a circumferential fashion
* 5mL injected into the ankle joint This cocktail includes 200 mg of 0.8% ropivacaine, 0.6 mg of epinephrine, 5 mg of morphine sulfate, and sodium chloride solution. All infiltrations will be completed with a blunt trochar to minimize the risk of intravascular injection.

Interventions:

Drug: Ropivacaine Drug: Epinephrine Drug: Morphine Drug: 0.9% sodium chloride solution Following surgery, patients in the treatment and non-treatment groups will both be provided with the same intravenous (patient-controlled analgesia) and oral pain medications scheduled "per needed". arm 2: Ankle fracture fixation/instrumentation will be completed per the standard of care. No peri-incisional injection will be completed.
Interventions: intervention 1: Ropivacaine intervention 2: Epinephrine intervention 3: Morphine intervention 4: 0.9% sodium chloride solution
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents:
Prot_000.pdf: 
Study Title:  
Efficacy of Multimodal Periarticular Injections in Operatively Treated Ankle Fractures: A 
Randomized Controlled Trial 
Date: 8/8/2016  
NCT: NCT02967172 


Study Protocol: 
Periarticular fractures (bone breaks extending into the joint surface) treated by orthopaedic 
surgeons are associated with significant pain in the post-operative period, often requiring high 
doses of opioid analgesics. In recent years, the high risk of misuse, abuse, and death associated 
with prescription opioid use has become increasingly evident. Although physicians are being 
advised to avoid administration of opioid prescriptions, alternative pain management options are 
limited. Currently, there is a need to investigate different pain management models in order to 
provide safe and effective pain relief during the post-operative period. 
 
We aim to evaluate the effectiveness of peri-incisional multimodal injections as an alternative 
post-operative pain control method in orthopaedic trauma patients with operative ankle fractures. 
Approximately 200 patients will be randomized to either receive or not receive intra-operative 
injections in addition to standard opioid analgesic regimens. Post-operative pain management 
outcomes will be assessed and compared between the 2 study groups to determine effectiveness 
of the injections. 
 
The proposed study will build upon related work to advance post-operative pain control 
regimens in orthopaedic surgery. Goals include the reduction of unnecessary patient suffering, 
reliance on opioids, and length of stay, while improving patient experience. These aims will be 
accomplished through the expansion of currently used multimodal periarticular injections from 
populations undergoing elective surgery to orthopaedic trauma patients with rotational ankle 
fractures. 
 
The study design is a prospective, double-blinded, randomized controlled trial. Patients included 
in the study will be randomly assigned to one of two treatment groups: intra-operative 
multimodal periarticular injection or control (no injection). The peri-incisional injection will 
consist of ropivacaine, epinephrine, and morphine. All pharmacologic agents in the anesthetic 
cocktail are FDA approved and have been previously used in combination during other types of 
orthopaedic surgeries. 
 
All patients included in the study will receive standard post-operative opioid analgesic regimens, 
administered ‘per needed’, regardless of their assigned treatment group per study protocol. ≥ 40 
patients will be randomly assigned to each group. The patients enrolled in the investigation as 
well as health care professionals performing post-operative assessments and collecting data will 
be blinded to treatment allocation. 
 
The feasibility of multimodal peri-incisional injections is supported by their current efficacy in 
populations undergoing elective orthopedic surgeries. These injections may be equally effective 
at reducing pain compared to regional anesthesia with continuous infusions, and single-shot 
nerve blocks.[7, 8] 


 
We hypothesize that the injection cohort will have reduced pain scores, lower narcotic 
requirements, shorter length of stay, and be more likely to discharge to home following surgery. 
We aim to evaluate the effectiveness of peri-incisional multimodal injections as an alternative 
post-operative pain control method in orthopaedic trauma patients with operative, closed, 
rotational ankle fractures. Patients undergoing surgical internal fixation of such fractures will be 
randomized to either receive or not receive intra-operative injections in addition to standard 
opioid analgesic regimens. 
 
Control group will receive no injection and will receive IV and oral analgesics post-operatively. 
 
Treatment group will receive injection during surgery into the periarticular space of ropivacaine, 
morphine, and epinephrine. They will also be provided with IV and oral analgesics post-
operatively. 
 
We will evaluate effectiveness of intra-operative injections by assessing inter-group differences 
in post-operative pain management outcomes, including: (1) subjective patient pain levels via 
visual analog scales in the immediate postoperative period; (2) quantity of opioid analgesics 
required prior to discharge; (3) post-operative length of stay; (4) discharge status (e.g. SNF, 
Rehab, Home). 
 
We hypothesize that the injection cohort will have reduced pain scores, lower narcotic 
requirements, shorter length of stay, and be more likely to discharge to home following surgery. 
Following consent, patients will be randomized by the research team using Microsoft Word (R) 
Random Number Generator. 
 
Patients will be blinded as to whether they received the injection or not. This is possible as they 
will be unconscious in surgery during their procedure. While an inpatient, the patients will be 
notified that they may ask which arm of the study they are in during their 3 month followup 
visit***. Until then they will stay blinded. 
 
They will then be treated with internal fixation of their fracture(s) as per standard of care. 
 
*** 
During this surgery, patients randomized to the peri-incisional injection cohort will receive a 
single, 25 mL intra-operative injection with medication following completion of fracture fixation 
and just prior to skin closure. The injection will be administered as such: 
20 mL injected into the peri-incisional soft tissues in a circumferential fashion. 
5mL injected into the ankle joint. 


This will take approximately 2 minutes of total surgery time. 
 
Following surgery, patients in the treatment and non-treatment groups will both be provided with 
the same intravenous (patient-controlled analgesia) and oral pain medications scheduled "per 
needed". 
 
Following surgery, (and again at their followup visits up to 3 months following surgery) the 
research team will examine the patient medical record and record narcotic use by the patient 
during their hospital stay. They will also record clinical outcomes from the medical record. 
(Notably VAS score). At 3 months the patient will no longer be followed in the study. At this 
point, the patients requesting information on which treatment arm they were in can be told. 
 
No follow-up after 3 months. 

SAP_001.pdf: 
Study Title:  
Efficacy of Multimodal Periarticular Injections in Operatively Treated Ankle Fractures: A 
Randomized Controlled Trial 
Date: 8/8/2016 
NCT: NCT02967172 


Statistical Analysis Plan: 
We will compare the two groups by improvement in the following measures: 
 
Visual Analog Scores scores recorded as Standard of Care during daily rounds 
Patient controlled analgesia usage as recorded as Standard of Care in Medical Record 
Time spent in hospital 
Standard of care outcome measures noted in Patient Medical Record 
 
Standard statistical analysis will be performed to analyze differences between groups. ANOVA, 
T-Test, and Kolmogorov-Smirnov, and other tests will be used. 
 
Based on a power analysis we estimate a minimal sample size of forty patients in each group to 
detect a 1.5 point difference in the Visual Analog Score (VAS) at each recording, with a standard 
deviation of 2.0 points, a p-value of .05, and a power of 80% or higher. Additional subjects (total 
subjects = 200) will aid in subgroup analyses, and ensure that we maintain an adequate sample 
size even if we run into issues with patient compliance (e.g. refusal of VAS during post-op stay) 
or unintentional de-blinding (nurse, student, resident etc. accidentally telling patient their 
treatment assignment) following the procedure.