Lidocaine for opioid sparing in vaso-occlusive crisis of Sickle Cell Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2025-11-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

French Ministry of Health

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine whether adding lidocaine to standard of care in pain management during sever vaso-occlusive crisis has an effect on the cumulative opioid consumption expressed as morphine milligram equivalent (MME).

Secondary objectives 10

1. Compare between groups intensive care unit length of stay at D28
2. Compare between groups hospital length of stay at D28
3. Compare between groups the pain intensity as evaluated using a Visual Analogue pain Scale (VAS) and Categorical Pain Score (CPS) during the intensive care unit stay
4. Compare between groups the time to vaso-occlusive crisis resolution
5. Compare between groups the time to last parenteral opioid dose
6. Compare between groups vaso-occlusive crisis complications during intensive care unit stay
7. Compare between groups the quality of life with reduced impact of sick cell-disease on health at D28
8. Compare between groups safety profile of lidocaine infusion at D28
9. Compare between groups the rate of readmission for vaso-occlusive crisis after intensive care unit discharge at D28
10. Assess the economic efficiency of lidocaine added to standard of care compared to standard of care alone in the management of severe vaso-occlusive crisis.

Conditions and MedDRA coding

Sickle cell disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥18 years
2. Known sickle cell disease with an SS, SC, Sβ0, or Sβ+ genotype
3. 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.
4. Treatment with parenteral morphine or oxycodone started less than 72 hours prior to inclusion
5. 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
6. French speaking
7. Patient with health care insurance

Exclusion criteria 20

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cumulative parenteral opioid dose between randomisation and discharge from the intensive care unit expressed in morphine milligram equivalent. Only parenteral morphine and parenteral oxycodone will be taken in account, as tramadol and codein are weak opioids, and stronger opioids like fentanyl or sufentanyl are not likely to be used for spontaneously breathing patients.

Secondary endpoints 10

1. Intensive care unit length of stay, in days, from randomisation
2. Hospital length of stay, in days, from randomisation
3. Visual Analogue pain Scale score and Categorical Pain Score score during intensive care unit stay
4. Time from randomisation to vaso-occlusive crisis resolution, defined as presence of at least three of the following four criteria: continuous apyrexia for the last 8 hours, no need for intravenous opioid infusion for the last 8 hours, ability to walk or move without pain, and absence of spontaneous pain with a Categorical Pain Scale ≤1
5. Time from randomisation to the last parenteral opioid dose
6. Frequency of vaso-occlusive crisis complications: a) secondary acute chest syndrome (i.e. acute chest syndrome occurring after randomisation), b) need for blood transfusion, c) need for red blood cell exchange, d) need for life-supporting therapies defined as invasive mechanical ventilation or dialysis or vasopressor support
7. Score of French version of Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) at D28
8. Frequency of any adverse events and frequency of serious adverse events at D28
9. Frequency of re-admissions in hospital (medicine ward or intensive care unit) or emergency-room visits by D28
10. Incremental cost-effectiveness ratio (cost par Quality-Adjusted Life-Year, QALY) comparing lidocaine + standard of care to standard of care alone

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Maïté AGBAKOU

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Maïté AGBAKOU

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications