Clinical trial NCT03770208: RIB PAIN (Rib Fractures Treated With Parental Analgesia With Infused LidocaiNe)
Official title: A Randomized Control Trial of Intravenous Lidocaine for the Management of Traumatic Rib Fractures: a Single Trauma Centre Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Rib Fracture Multiple
Pain, Chest
Pain, Acute
Respiratory Failure
Thoracic Injuries
Trauma Chest
Keywords: Lidocaine Infusions
Thoracic trauma
Analgesic Management
Rib Fractures
Pain
Lead sponsor: Western University, Canada
Sponsor class: OTHER
First posted: 2018-12-10
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RCT, single site, double blinded
Primary purpose: TREATMENT

Brief summary: Traumatic rib fractures (RF) are a relatively common occurrence in patients of all ages, with a 10% incidence in all trauma patients and are associated with significant morbidity and mortality. Adequate analgesia is paramount for preventing pulmonary complications and can reduce morbidity and mortality. There is longstanding evidence of lidocaine's effectiveness and safety in the post-operative patient and the investigators hypothesize that this modality may prove to be ideal in trauma patients with RF. Therefore, it is imperative that intravenous lidocaine be investigated to ascertain if there is significant benefit for pain reduction in patients who have sustained rib fractures.

A single-centre, double-blind, randomized control trial to evaluate the analgesic efficacy of a 72-96 hour IV lidocaine infusion plus standard analgesics versus placebo infusion plus standard analgesics will be performed on patients (age 18 or older) diagnosed with two or more traumatic rib fractures ,from blunt thoracic trauma, requiring hospital admission at Victoria Hospital.

The primary outcome is mean pain score, as measured on the Visual Analog Scale (VAS) when the patient is at rest and with movement. Secondary outcomes are protocol adherence, patient satisfaction as measured on the VAS, incidence of respiratory failure requiring mechanical ventilation, hospital length of stay, ICU length of stay, mortality, incidence of lidocaine toxicity, treatment regimens (use of additional non-opioid analgesics) and total morphine equivalents used (including breakthrough doses).

This trial will serve to quantify the analgesic efficacy of intravenous lidocaine for patients with traumatic rib fractures. Successful completion of a single centre trial will inform the development of a multi-centre trial powered to demonstrate a reduction in respiratory failure in the trauma population.

Detailed description: This trial will use a randomized double blind design. All patients (age 18 or older) diagnosed with two or more traumatic rib fractures requiring hospital admission at Victoria Hospital will be identified at the time of admission by trauma team members and / or ICU research assistants. Patients unable to understand or follow instructions in English or French, and those unable to complete the Visual Analog Scale (VAS) for pain for any reason, will be excluded.

Any physician member of the inpatient trauma service team, trauma nurse practitioner, or ICU research assistants may approach patients and their families to discuss participation in the trial. Research assistants will be responsible for providing the Letter of Information and Consent Form to families, and storing them once complete. Consented patients will be randomized at admission using the online randomization tool, like REDCAP, by pharmacy. Once randomized, research assistants will contact pharmacy to order "Study Drug", but will remain blinded to study arm

Consented patients will receive either standard care (acetaminophen, NSAIDs, opioids) plus IV placebo or standard care plus IV lidocaine using a fixed strategy with variable blocks and a 1:1 allocation ratio. The pharmacy will be the only party unblinded to randomization and will distribute the "Study Drug" \[either IV lidocaine or Lactated Ringer's (a clear colourless solution that is indistinguishable from Lidocaine)\] to study participants. All patients will be followed throughout their hospital stay by our research assistants to assess pain and secondary outcomes.

IV lidocaine will be administered as a bolus dose of 2 mg/kg (maximum dose 100 mg) followed by a 2 mg/kg/hr infusion for 72-96 hrs. Lactated Ringer's will be administered at the same overall rate to the control group. Patient pain scores will be accessed at the bedside using the VAS at time 0hrs and every six hours for the duration of study drug infusion.

Daily monitoring of the patient will be performed by the trauma team and bedside nurses. Clinical care will be conducted as usual with the exception of the provision of study drug, the recording of pain Q6 hours, and the assessment of patient satisfaction at the end of the 72-96 hour infusion. All other patient data will be collected from the patient's EMR and bedside chart. In accordance with LHSC hospital Lidocaine policy, all study patients will be on telemetry to monitor for arrhythmias resulting from lidocaine toxicity. As the use of IV lidocaine is already common in the LHSC patient population, all nursing staff are trained to detect signs and symptoms of lidocaine toxicity, and will contact the treatment and research teams if these develop. The study drug infusions will be stopped if any signs of toxicity are seen. The treating team will be unblinded to randomization group in any cases of suspected Lidocaine toxicity.

The primary outcome will be mean pain score calculated from the multiple VAS measures performed during Lidocaine infusions when the patient is at rest and with movement. Secondary outcomes are protocol adherence, patient satisfaction as measured on the VAS, incidence of respiratory failure requiring mechanical ventilation, hospital length of stay, ICU length of stay, mortality, incidence of lidocaine toxicity, treatment regimens (use of additional non-opioid analgesics) and total morphine equivalents used (including breakthrough doses). Secondary outcomes will be recorded by the ICU research assistants on a daily basis during each patient's index stay. Research assistants will help administer the satisfaction survey to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion. The methodology, pain and satisfaction reporting with VAS is very similar to the investigator's previous work.

A sample size of 26 patients is required to find a difference between two independent group means using the following parameters: (1) a 20% reduction in VAS score (20mm), (2) 90% power, (3) probability of a Type I error = 5%, and s stand deviation of 15% (15mm).

An anticipated attrition rate of 20% will be used to ensure enough patients are included for adequate power. Therefore a minimum of 32 patients will be enrolled in the study.

Continuous data will be reported as mean +/- standard deviation or median and interquartile range, depending on the distribution of each data point. Categorical data will be reported as percentages with corresponding 95% confidence intervals. The mean pain score will be compared between treatment groups using Student's T-test. Findings with a Type I error rate \< 5% will be considered statistically significant. Analyses of secondary outcomes will be primarily descriptive. Any significance testing of these outcomes will be strictly hypotheses-generating.

Eligibility criteria: Inclusion Criteria:

* All adult patients, 18 years or older, admitted to Victoria Hospital's Trauma Service with two or more traumatic rib fractures.

Exclusion Criteria:

* Patients under 18 years old
* Patients who sustained complex trauma with multiple other injuries or have decreased LOC or required intubation at admission
* Patients with a known allergy/sensitivity to Lidocaine or other local anesthetic, amide anesthetics or components of the solution
* Patients with a known history of hypersensitivity to methylparaben and/or propylparaben (preservatives used in multidose solutions), or to their metabolite para amino benzoic acid
* Patients who do not speak English with adequate fluency to consent or participate in the VAS survey
* Patients receiving epidural analgesia for another reason
* Patients with pre-existing cardiac arrhythmias including Adam-Stokes syndrome; Wolff- Parkinson-White syndrome; and severe degrees of sinoatrial, atrioventricular, or intraventricular heart block (except in patients with a functioning artificial pacemaker)
* Patients who are known to be pregnant or breast feeding, as identified on Past Medical History, or by initial laboratory investigations performed as a part of standard trauma team assessment
* Patients with known hepatic/renal disease, as identified on Past Medical History, or by initial laboratory investigations performed as a part of standard trauma team assessment
* Patients who refuse inclusion

Primary outcomes:
measure: Mean Visual Analogue Scale (VAS) Score for Pain
timeFrame: Pain score to be measured before treatment initiation and every 6 hours thereafter until 72-96 hours. Scores will be performed by bedside nursing.
Secondary outcomes:
measure: Incidence of Protocol Non-adherence
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Patient satisfaction as measured on the Visual Analogue Scale for Satisfaction
timeFrame: Research assistants will help administer the satisfaction survey to patients as soon as possible following completion of the 72-96 hour Lidocaine infusion.
measure: Incidence of respiratory failure requiring mechanical ventilation
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Hospital length of stay
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: ICU length of stay
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Incidence of Mortality
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period or when the mortality occurs.
measure: Incidence of lidocaine toxicity/adverse events
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Treatment regimens (use of additional non-opioid analgesics): Medication type
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Treatment regimens (use of additional non-opioid analgesics): Dosages
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Treatment regimens (use of additional non-opioid analgesics): Frequency
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Treatment regimens (use of additional non-opioid analgesics): Delivery Route
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
measure: Total morphine equivalents used (including breakthrough doses)
timeFrame: Will be recorded by the ICU research assistants at the end of each patient's 72-96 hour study period.
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
Study officials:
affiliation: London Health Sciences Centre
name: Ian Ball, MD, MSc (Epi), FRCPC
role: PRINCIPAL_INVESTIGATOR
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