Evaluation of Lidocaine Hydrochloride and Sodium Chloride for Opioid Reduction in Vaso-Occlusive Crisis Management in Sickle Cell Disease

Trial ID: 2024-518437-28-00
Protocol: RC24_0427
Sponsor: Centre Hospitalier Universitaire De Nantes

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Diseases & Conditions

Sickle cell disease

Objectives

The primary objective is to evaluate whether the addition of lidocaine to the standard of care influences the cumulative opioid consumption, measured in morphine milligram equivalent (MME), during a severe vaso-occlusive crisis associated with sickle cell disease. 5

Secondary objectives include the assessment of:

Intensive care unit and hospital length of stay at day 28.
Pain intensity measured via Visual Analogue Scale (VAS) and Categorical Pain Score (CPS) during the intensive care unit stay.
Time to resolution of the vaso-occlusive crisis and time to the final parenteral opioid dose.
Complications related to the vaso-occlusive crisis during the intensive care unit stay.
Quality of life and the impact of the disease on health at day 28.
The safety profile of the lidocaine infusion at day 28.
The rate of readmission for vaso-occlusive crisis following intensive care unit discharge at day 28.
Economic efficiency of adding lidocaine to the standard of care.

Participants

The sponsor did not provide information regarding the total number of participants. The study population consists of adults with sickle cell disease, specifically those possessing an SS, SC, Sβ0, or Sβ+ genotype. Participants include both male and female patients who are admitted to the intensive care unit due to a vaso-occlusive crisis or acute chest syndrome. Inclusion requires that parenteral morphine or oxycodone treatment was initiated less than 72 hours prior to enrollment. The population is identified as a vulnerable group.

Plans and Procedures

This Phase III clinical trial is designed to evaluate the efficacy of lidocaine hydrochloride compared to sodium chloride for opioid sparing in the management of sickle cell disease during a vaso-occlusive crisis. The study utilizes a randomized approach to determine the impact of adding lidocaine to the standard of care on the cumulative parenteral opioid consumption, measured as morphine milligram equivalent. Following a screening process to confirm eligibility based on genotype, age, and clinical presentation, participants are randomized and receive either the test product or a placebo via parenteral use. The primary endpoint is the cumulative opioid dose administered between randomization and discharge from the intensive care unit. Secondary endpoints include the intensive care unit length of stay, hospital length of stay, and various pain scale scores. Monitoring includes follow-up assessments to evaluate acute chest syndrome complications, quality of life, and the frequency of adverse events through day 28. The trial is estimated to be conducted between January 2026 and February 2028.

Treatment

The experimental treatment consists of lidocaine hydrochloride administered via parenteral use at a dosage of 3060 mg.

The control group receives sodium chloride as a placebo via parenteral use at a dosage of 3060 mg.

Efficacy

The efficacy assessment for sickle cell disease focuses on the impact of lidocaine hydrochloride on opioid sparing during a vaso-occlusive crisis. The primary endpoint is the cumulative parenteral opioid dose, measured in morphine milligram equivalent (MME), administered from the time of randomization until discharge from the intensive care unit. This calculation includes only parenteral morphine and parenteral oxycodone.

Secondary endpoints include several clinical parameters:

Intensive care unit length of stay and hospital length of stay, measured in days from randomization.
Pain assessment using the Visual Analogue Scale and Categorical Pain Score during the intensive care unit stay.
The time from randomization to vaso-occlusive crisis resolution, determined by criteria including continuous apyrexia, cessation of intravenous opioid infusion, mobility without pain, and a Categorical Pain Scale score of ≤1.
The interval from randomization to the final parenteral opioid dose.
The frequency of complications, such as acute chest syndrome, blood transfusion, red blood cell exchange, or the requirement for life-supporting therapies like invasive mechanical ventilation, dialysis, or vasopressor support.
The score of the French version of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) at day 28.
The frequency of adverse events, serious adverse events, and hospital re-admissions or emergency-room visits by day 28.
The incremental cost-effectiveness ratio, calculated as cost per Quality-Adjusted Life-Year (QALY), comparing lidocaine with standard of care to standard of care alone.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥18 years
Known sickle cell disease with an SS, SC, Sβ0, or Sβ+ genotype
Patient admitted to the intensive care unit for vaso-occlusive crisis and/or acute chest syndrome as the main reason for admission : Vaso-occlusive crisis defined by acute pain or tenderness, affecting at least one part of the body, including limbs, ribs, sternum, head (skull), spine, and/or pelvis, not attributable to other cause / Acute chest syndrome defined by the association of clinical respiratory sign(s): dyspnea and/or chest pain and/or auscultatory abnormality (crepitants and/or bronchial breathing) with a new pulmonary infiltrate on chest X-ray, thoracic CT-scan, or lung ultrasound.
Treatment with parenteral morphine or oxycodone started less than 72 hours prior to inclusion
Patient or next of kin informed about the study and having consented to participation of the patient in the study. If patient is no competent and no next of kin can be contacted during screening for the study, trial inclusion will be completed as an emergency procedure by the intensive care unit physician, in compliance with French law
French speaking
Patient with health care insurance

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Exclusion Criteria

Pregnant women or nursing mothers; Women of child bearing potential will be tested for pregnancy before inclusion
Epileptic patients
Hypovolemic shock or shock of other cause at screening for inclusion
Known atrioventricular block, QT prolongation or other heart conduction disorder or heart failure
Chronic respiratory failure with long term non invasive ventilation (excluding Continuous Positive Air way pressure), or long term oxygen therapy at home
Acute Respiratory Distress Syndrome according to The 2012 Berlin definition
Acute or Chronic liver failure with MELD > 19 according to CKD-EPI
Acute or Chronic kidney failure with clearance <30mL/min/m2
Body weight <40kg and >120kg
Prior inclusion in the study in the last 3 months
Patients under guardianship, curatorship or under legal protection
Prisoners or subjects who are involuntarily incarcerated
Sickle cell disease acute complication other than vaso-occlusive crisis or acute chest syndrome as the main reason for admission : priapism, stroke, acute splenic sequestration, acute hepatic sequestration, bone marrow necrosis.
Patients wearing a lidocaine-medicated plaster at the time of screening for inclusion
Known or assumed hypersensitivity to lidocaine hydrochloride, other local anaesthetics (e.g., bupivacaine or ropivacaine) or an excipient
Patients treated with anti-arhythmic drugs known to induce torsade de pointe
Patients on chronic or occasional treatment with drugs that interact with the 3A cytochrome isoenzymes (CYP3A) and/or 1A2 cytochrome isoenzymes (CYP1A2)
Patients with recurrent porphyria, porphyria in remission, or known asymptomatic carriage of gene mutations responsible for porphyria
Patient under invasive mechanical ventilation
Altered consciousness with Glasgow coma scale <13