Lidocaine for Opioid Sparing in Vaso-occlusive Crisis of Sickle Cell Disease

Overview

The purpose of the study is to determine whether adding lidocaine to standard of care in pain management during severe vaso-occlusive crisis has an effect on the cumulative opioid consumption expressed as morphine milligram equivalent.

Interventions

• Drug Lidocain
  Lidocaine hydrochloride 20 mg/mL, solution, 20 mL ampoule for IV administration (25 ampoules) Administration : parenteral route on peripheral or central venous catheter. - Bolus of 1.5 mg/kg bolus dur
• Drug Placebo
  Placebo is 20 mL ampoules of sodium chloride (NaCl 0.9%) for injection Administration : parenteral route on peripheral or central venous catheter. * Bolus of 1.5 mg/kg bolus during 30 minutes, with a maxium dose of 180 mg (18mL) * Immediately followed by a continuous infusion of 1 mg/kg/h (max 120mg/h = 12mL/h) during 72 hours.
• Drug Standard of care
  Standard of care

Primary outcome measures

• Cumulative parenteral opioid dose between randomization and discharge from the intensive care unit expressed in morphine milligram equivalent. [Time frame: up to 28 days]

Secondary outcome measures (12)

• Intensive Care Unit length of stay [Time frame: up to 28 days]
• hospital length of stay [Time frame: up to 28 days]
• Visual analogue pain Scale score during Intensive Care Unit stay [Time frame: up to 28 days]
• Categorical Pain Score during Intensive Care Unit stay [Time frame: up to 28 days]
• Time of resolution of severe vaso-occlusive crisis [Time frame: up to 28 days]
• time to last parenteral opioid dose [Time frame: up to 28 days]
• vaso-occlusive crisis complications during Intensive Care Unit stay [Time frame: up to 28 days]
• vaso-occlusive crisis complications during Intensive Care Unit stay [Time frame: up to 28 days]
• vaso-occlusive crisis complications during Intensive Care Unit stay [Time frame: up to 28 days]
• vaso-occlusive crisis complications during Intensive Care Unit stay [Time frame: up to 28 days]
• quality of life with reduced impact of Sickle Cell Disease on health [Time frame: At Day 28]
• safety profile of lidocaine infusion [Time frame: at 28 days]

Eligibility criteria

Inclusion criteria

• Age >= 18 years
• Known sickle cell disease with an SS, SC, Sβ, or Sβ+ genotype
• Patient admitted to the Intensive Care Unit for Vaso-Occlusive Crisis and/or ACS 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 causes
• 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 the 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

Exclusion criteria

• Pregnant women or nursing mothers; Women of child bearing potential will be tested for pregnancy before inclusion
• 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
• 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
• Patient under invasive mechanical ventilation
• Altered consciousness with Glasgow coma scale <13

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

France · 10 centers

• CHU Bordeaux — Bordeaux
• CHU Lille — Lille
• CHU La Timone — Marseille
• CHU de Nantes — Nantes
• CHU Orléans — Orléans
• Hôpital Tenon APHP — Paris
• CHU Poitiers — Poitiers
• CHU Rouen — Rouen
• … and 2 more centers

Guadeloupe · 1 center

• CHU Guadeloupe — Les Abymes

Identifiers

NCT: NCT07274254 · RC24_0427

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗