Lidocaine Intravenous in the Emergency Department For Sickle Cell Crisis

Sickle Cell Disease Clinical Trial

— RELIEF-SCC  

Official title:

Randomized Trial Evaluating Lidocaine Intravenous in the Emergency Department For Sickle Cell Crisis - RELIEF-SCC

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04614610
• Other study ID #: 20-58
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2024
• Est. completion date: June 1, 2025

Study information

• Verified date: August 2023
• Source: Community Medical Center, Toms River, NJ
• Contact: Andrew V Vassallo, PharmD
• Phone: 732-557-8070
• Email: Andrew.Vassallo[@]rwjbh.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 1, 2025
• Est. primary completion date: January 2, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Pain
• Anemia, Sickle Cell
• Emergencies
• Pain, Acute
• Sickle Cell Crisis
• Sickle Cell Disease

Intervention

Drug:
• Lidocaine Iv
Lidocaine 1.5mg/kg (Max dose: 200mg) in Dextrose 5% 100mL over 10 minutes
• Placebo
Dextrose 5% 100mL over 10 minutes

Locations

Country	Name	City	State
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Newark Beth Israel Medical Center	Newark	New Jersey

Sponsors (4)

Lead Sponsor	Collaborator
Community Medical Center, Toms River, NJ	Monmouth Medical Center, Newark Beth Israel Medical Center, Rutgers Robert Wood Johnson Medical School

Country where clinical trial is conducted

United States, 

References & Publications (13)

Bijur PE, Latimer CT, Gallagher EJ. Validation of a verbally administered numerical rating scale of acute pain for use in the emergency department. Acad Emerg Med. 2003 Apr;10(4):390-2. doi: 10.1111/j.1553-2712.2003.tb01355.x. — View Citation

Carroll CP, Lanzkron S, Haywood C Jr, Kiley K, Pejsa M, Moscou-Jackson G, Haythornthwaite JA, Campbell CM. Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease. Am J Prev Med. 2016 Jul;51(1 Suppl 1):S69-77. doi: 10.1016/j.amepre.2016.02.012. — View Citation

E Silva LOJ, Scherber K, Cabrera D, Motov S, Erwin PJ, West CP, Murad MH, Bellolio MF. Safety and Efficacy of Intravenous Lidocaine for Pain Management in the Emergency Department: A Systematic Review. Ann Emerg Med. 2018 Aug;72(2):135-144.e3. doi: 10.1016/j.annemergmed.2017.12.014. Epub 2018 Feb 1. — View Citation

Eipe N, Gupta S, Penning J. Intravenous Lidocaine for Acute Pain: an Evidence-based Clinical Update. BJA Education,16(9):292-298(2016). Doi: 10.1093/bjaed/mkw008

Firouzian A, Alipour A, Rashidian Dezfouli H, Zamani Kiasari A, Gholipour Baradari A, Emami Zeydi A, Amini Ahidashti H, Montazami M, Hosseininejad SM, Yazdani Kochuei F. Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, randomized controlled trial. Am J Emerg Med. 2016 Mar;34(3):443-8. doi: 10.1016/j.ajem.2015.11.062. Epub 2015 Dec 1. — View Citation

Holdgate A, Asha S, Craig J, Thompson J. Comparison of a verbal numeric rating scale with the visual analogue scale for the measurement of acute pain. Emerg Med (Fremantle). 2003 Oct-Dec;15(5-6):441-6. doi: 10.1046/j.1442-2026.2003.00499.x. — View Citation

Lanzkron S, Carroll CP, Haywood C Jr. The burden of emergency department use for sickle-cell disease: an analysis of the national emergency department sample database. Am J Hematol. 2010 Oct;85(10):797-9. doi: 10.1002/ajh.21807. — View Citation

Lexicomp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; December 15, 2017.

Motov S, Fassassi C, Drapkin J, Butt M, Hossain R, Likourezos A, Monfort R, Brady J, Rothberger N, Mann SS, Flom P, Gulati V, Marshall J. Comparison of intravenous lidocaine/ketorolac combination to either analgesic alone for suspected renal colic pain in the ED. Am J Emerg Med. 2020 Feb;38(2):165-172. doi: 10.1016/j.ajem.2019.01.048. Epub 2019 Jan 30. — View Citation

Nguyen NL, Kome AM, Lowe DK, Coyne P, Hawks KG. Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease. J Pain Palliat Care Pharmacother. 2015;29(4):359-64. doi: 10.3109/15360288.2015.1082009. — View Citation

Payne J, Aban I, Hilliard LM, Madison J, Bemrich-Stolz C, Howard TH, Brandow A, Waite E, Lebensburger JD. Impact of early analgesia on hospitalization outcomes for sickle cell pain crisis. Pediatr Blood Cancer. 2018 Dec;65(12):e27420. doi: 10.1002/pbc.27420. Epub 2018 Aug 27. — View Citation

Rousseau V, Morelle M, Arriuberge C, Darnis S, Chabaud S, Launay V, Thouvenin S, Roumenoff-Turcant F, Metzger S, Tourniaire B, Marec-Berard P. Efficacy and Tolerance of Lidocaine 5% Patches in Neuropathic Pain and Pain Related to Vaso-occlusive Sickle Cell Crises in Children: A Prospective Multicenter Clinical Study. Pain Pract. 2018 Jul;18(6):788-797. doi: 10.1111/papr.12674. Epub 2018 Feb 28. — View Citation

Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urol. 2012 May 4;12:13. doi: 10.1186/1471-2490-12-13. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in pain at 30 minutes	Change of visual analog pain scale (VAS, 0-10) at 30 minutes post-infusion of lidocaine or placebo.	from pre-lidocaine infusion to 30 minutes post-infusion
Secondary	Total opiate dosage received	Total morphine mg equivalents (MME) of opiate received normalized to patient's bodyweight during their ED stay.	from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
Secondary	% Patients requiring additional opiate administration	Percentage of patients requiring an additional opiate after the lidocaine vs. placebo.	from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
Secondary	Time to next opiate administered	Time (minutes) until next opiate is administered after lidocaine vs. placebo.	from administration of lidocaine infusion until patient disposition (up to 12 hours) or next opiate administered
Secondary	Total MME post-lidocaine up to 12 hours	Total MME needed after lidocaine vs placebo up to 12 hours	12 hours post-lidocaine or placebo infusion.
Secondary	Percentage of patients discharged from ED	Percentage of patients discharged from the ED.	from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
Secondary	Percentage of patients receiving a >20% reduction in pain scale	Percentage of patients receiving a >20% reduction in pain scale based on the VAS (0-10).	from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)
Secondary	Change in visual analog pain scale (VAS, 0-10 with 10 being the most pain) at 60 and 90 minutes	Change in VAS at 60 and 90 minutes post-infusion.	60 and 90 minutes
Secondary	Number of adverse effects of treatment	Reported adverse effects during study treatment period	from presentation to the Emergency department (ED) until patient disposition (up to 12 hours)