Clinical trial NCT04614610: Lidocaine Intravenous in the Emergency Department For Sickle Cell Crisis
Official title: Randomized Trial Evaluating Lidocaine Intravenous in the Emergency Department For Sickle Cell Crisis - RELIEF-SCC
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Sickle Cell Crisis
Pain, Acute
Keywords: lidocaine
ALTO
sickle cell pain
Lead sponsor: Community Medical Center, Toms River, NJ
Sponsor class: OTHER
Collaborators: name: Newark Beth Israel Medical Center
name: Monmouth Medical Center
name: Rutgers Robert Wood Johnson Medical School
First posted: 2020-11-04
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients presenting to the emergency department for an acute sickle cell crisis who are refractory to one dose of intravenous opiate therapy will be randomized to either lidocaine 1.5mg/kg (max: 200mg) or matching dextrose placebo along with either morphine 0.1-0.15mg/kg IV or hydromorphone 0.01-0.02mg/kg IV.
Primary purpose: TREATMENT

Brief summary: Sickle cell crisis continues to be a frequent presentation to emergency departments. Patients presenting will often require immediate treatment for their pain and often times this will include opioids. The opioid epidemic has cost thousands of lives; and continues to be a significant problem posing several challenges when treating patients presenting with sickle cell disease. Primarily, opioids remain the mainstay of treatment for these patients and the push to address the opioid crisis may present challenges for adequate opioid administration in patients suffering from a sickle cell crisis while hospitals find ways to curb the opioid crisis overall. Opioid treatment for patients in acute vaso-occlusive crisis has significantly contributed to quality of life and life expectancy of patients with this diagnosis. Measures should continue to attempt to administer a multi-model approach to sickle cell patients to minimize the morphine milligram equivalents in these patients while also successfully addressing the patient's pain. IV lidocaine is a pain medication that has been evaluated in several painful experiences, such as in renal colic. A few case reports have shown IV lidocaine use in sickle cell can be a potential effective adjunct medication to opioids to treat pain and reduce further opioid requirements. Currently, no prospective controlled trial exists to evaluate the true benefit of IV lidocaine in this population. Our study aims to evaluate IV lidocaine as an adjunct to opioid treatment in the emergency department to determine if improved pain is achieved and if there is a reduction in overall morphine milligram equivalents throughout the emergency department visit.

Detailed description: Pain is the most frequent reason for emergency department visits in the United States, especially for those patients with sickle cell disease (SCD). Painful vaso-occlusive events frequently require admission to the hospital despite opioid therapy, which is the mainstay of treatment for moderate to severe pain in SCD. Achieving adequate pain control with escalating doses of opioid analgesics may be difficult due to tolerance, physical dependence, and side effects. Common side effects include pruritus, nausea and vomiting, constipation, urinary retention, sedation, and respiratory depression. With the recent focus on the opiate crisis there has been a push towards the use of alternative to opiates (ALTO) for a variety of pain syndromes.

Lidocaine is a class 1b sodium channel blocking agent that is typically used as an anti-arrhythmic and local anesthetic. This medication also has potent anti-inflammatory, anti-hyperalgesic, and gastrointestinal pro-peristaltic properties. Lidocaine may be useful as an adjunct to opioids in response to a painful sickle cell crisis. Intravenous (IV) lidocaine infusion has previously shown benefit in neuropathic pain, renal colic, and peri-operative pain. No prospective studies have evaluated lidocaine for SCD pain thus far.

A previous retrospective study evaluated lidocaine infusion as adjuvant therapy to patients with SCD. Eleven patients were given a total of 15 IV lidocaine trials. Investigators found clinical improvement in pain score from pre-lidocaine challenge to 24 hours post (defined as a \>20% reduction in pain scores) in 53.3% (8 of 15) of patients. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre to 24 hours post lidocaine was 32.2%. Two patients experienced disorientation and dizziness. The authors concluded that lidocaine was able to provide pain relief and reduce the amount of morphine necessary during SCD vaso-occlusive crisis and that prospective studies are needed to determine its true efficacy, dosing, and tolerability.

A prospective, single-arm, phase II trial evaluated lidocaine 5% patches for neuropathic pain and pain related to vaso-occlusive sickle cell crises in children ages 6 to 21 years old. Patches were applied to the painful area for 12 hours a day. The primary endpoint was the proportion of inpatients with significant pain relief defined as a decrease of at least 2 points on the visual analog pain scale (VAS, from 0-10) measured at 12 hours after patch placement over two consecutive days. The use of additional treatments such as antiepileptics and opioids were allowed and their usage was documented. The primary outcome of VAS improvement of \>2 over 2 consecutive days was observed in 48.6% of evaluated patients (19/39). Transdermal lidocaine was tolerated well with only 3 minor adverse events reported (two localized skin reactions and one generalized skin eruption) and no serious adverse events.

The theoretical benefits along with the two previously discussed studies provide evidence to further investigate the use of lidocaine in SCD pain. Studies are needed to know whether lidocaine may be able to benefit alleviate pain quicker and minimize need for opiates similarly to its use in renal colic. This prospective trial aims to evaluate whether lidocaine can decrease the opiate needs during a SCD crisis while providing adequate pain relief and tolerability.

Eligibility criteria: Inclusion Criteria:

* Patients \> 18 years old with sickle cell disease experiencing persistent severe (7-10/10) pain despite receiving at least one dose of intravenous opiate analgesic.

Exclusion Criteria:

* Patients \< 18 years old and pregnant
* Patients presenting with or suspected to have acute chest syndrome
* Allergy or intolerance to lidocaine products or morphine/hydromorphone

Primary outcomes:
measure: Change in pain at 30 minutes
timeFrame: from pre-lidocaine infusion to 30 minutes post-infusion
Secondary outcomes:
measure: Total opiate dosage received
timeFrame: from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
measure: % Patients requiring additional opiate administration
timeFrame: from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
measure: Time to next opiate administered
timeFrame: from administration of lidocaine infusion until patient disposition (up to 12 hours) or next opiate administered
measure: Total MME post-lidocaine up to 12 hours
timeFrame: 12 hours post-lidocaine or placebo infusion.
measure: Percentage of patients discharged from ED
timeFrame: from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
measure: Percentage of patients receiving a >20% reduction in pain scale
timeFrame: from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
measure: Change in visual analog pain scale (VAS, 0-10 with 10 being the most pain) at 60 and 90 minutes
timeFrame: 60 and 90 minutes
measure: Number of adverse effects of treatment
timeFrame: from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
Other outcomes:
Locations:
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
Study officials:
affiliation: Newark Beth Israel
name: Shreni Zinzuwadia, MD
role: PRINCIPAL_INVESTIGATOR
References:
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