Clinical trial • Phase IV • Other

NEFOPAM HYDROCHLORIDE for Intubation|Mechanical ventilation

Phase IV trial of NEFOPAM HYDROCHLORIDE for Intubation|Mechanical ventilation.

Overview

Trial Therapeutic Area
Other
Trial Disease
Intubation|Mechanical ventilation
Trial Stage
Phase IV
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
19-09-2024
First CTIS Authorization Date
17-10-2024

Trial design

Randomised, interventional strategy (opioid free): fixed combination of nefopam and tramadol initiated at daily doses of 400mg and 120mg respectively; initial dose of 50mg tramadol and 20mg nefopam ivl over 30 minutes; analgesia re-evaluated every 30 minutes for first 2 hours then every 2 hours. comparator (conventional strategy): combination of paracetamol and remifentanil with remifentanil doses adapted according to tiered administration based on bps and theoretical ideal weight; remifentanil doses adjusted in stages until bps ≤4; analgesia reassessed every 30 minutes until adaptation complete, then every 2 hours. placebo used: 0.9% sodium chloride (placebo).-controlled Phase IV trial across 1 site in France.

Randomised
Yes
Comparator
Interventional strategy (opioid free): fixed combination of nefopam and tramadol initiated at daily doses of 400mg and 120mg respectively; initial dose of 50mg tramadol and 20mg nefopam IVL over 30 minutes; analgesia re-evaluated every 30 minutes for first 2 hours then every 2 hours. Comparator (Conventional strategy): combination of paracetamol and remifentanil with remifentanil doses adapted according to tiered administration based on BPS and theoretical ideal weight; remifentanil doses adjusted in stages until BPS ≤4; analgesia reassessed every 30 minutes until adaptation complete, then every 2 hours. Placebo used: 0.9% sodium chloride (placebo).
Target Sample Size
50
Trial Duration For Participant
90

Eligibility

Recruits 50 Vulnerable population selected. Consent may be provided as: "Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure"; translated subject information and ICF documents exist for patient and proche..

Pregnancy Exclusion
Parturient or breast-feeding patient
Vulnerable Population
Vulnerable population selected. Consent may be provided as: "Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure"; translated subject information and ICF documents exist for patient and proche.

Inclusion criteria

  • {"criterion_text":"- Patient hospitalized in ICU and requiring sedation-analgesia for mechanical ventilation"}
  • {"criterion_text":"- Patient undergoing mechanical ventilation for more than 2 hours and less than 24 hours."}
  • {"criterion_text":"- Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure"}
  • {"criterion_text":"- Patient affiliated to the French Government Public Health Insurance"}
  • {"criterion_text":"- Patient over 18 years old"}

Exclusion criteria

  • {"criterion_text":"- Patient already involved in a trial that might influence our primary endpoint"}
  • {"criterion_text":"- Patient in exclusion-period determined by another trial or study"}
  • {"criterion_text":"- Patient who is likely to be requiring less than 48 hours of mechanical ventilation"}
  • {"criterion_text":"- Patient with contraindication or allergies to at least one of the following medication : paracetamol, nefopam, tramadol, ketamine, remifentanil"}
  • {"criterion_text":"- Patient with hepatic insufficiency (defined as PT < 50%)"}
  • {"criterion_text":"- Parturient or breast-feeding patient"}
  • {"criterion_text":"- Patient suffering from moderate to severe Acute Respiratory Distress Syndrome (ARDS), with decreased PaO2/FiO2 ratio under 150mmHg after respiratory optimization (courant volume 6mL/kg and PEEP > 5mbar)"}
  • {"criterion_text":"- Patient requiring curare treatment"}
  • {"criterion_text":"- Patient requiring ICU after undergoing major surgery (laparotomy or thoracotomy)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- daily consumption of remifentanil between the 24th hour and the 48th hour after randomisation of patients admitted to the ICU and requiring at least 72 hours of mechanical ventilation","definition_or_measurement_approach":"Measured as daily remifentanil consumption between 24 and 48 hours post-randomization (as stated in endpoint description)."}

Secondary endpoints

  • {"endpoint_text":"- Cumulative dose of remifentanil","definition_or_measurement_approach":"Measured as cumulative remifentanil dose over the observation period."}
  • {"endpoint_text":"- Number of lived days free of remifentanil","definition_or_measurement_approach":"Count of alive days without remifentanil exposure within the observation period."}
  • {"endpoint_text":"- Daily consumption of sedative drugs from inclusion to D28","definition_or_measurement_approach":"Measured as daily dose/consumption of sedative medications from inclusion through day 28."}
  • {"endpoint_text":"- Number of live days free of mechanical ventilation","definition_or_measurement_approach":"Count of days the patient is alive and free from mechanical ventilation during the follow-up period."}
  • {"endpoint_text":"- SOFA Score (Sepsis-related Organ Failure Assessment)","definition_or_measurement_approach":"Measured using the SOFA scoring system; changes/trends to be recorded."}
  • {"endpoint_text":"- Daily fuid intake in milliliter","definition_or_measurement_approach":"Measured as daily fluid intake (milliliters) related to analgesia."}
  • {"endpoint_text":"- CAM ICU test","definition_or_measurement_approach":"Assessment of delirium using the CAM-ICU test."}
  • {"endpoint_text":"- Presence of one or more events of special interest or expected adverse events: constipation, bradycardia, bladder globe, nausea, vomiting, liver disturbance, serotonin syndrome","definition_or_measurement_approach":"Recorded occurrence of listed adverse events of interest during follow-up."}
  • {"endpoint_text":"- Presence of pneumonia associated with mechanical ventilation","definition_or_measurement_approach":"Diagnosis/recording of ventilator-associated pneumonia during follow-up."}
  • {"endpoint_text":"- Extubation failure and cause (reintubation within 48 hours of first extubation)","definition_or_measurement_approach":"Extubation failure defined as reintubation within 48 hours of the first extubation."}
  • {"endpoint_text":"- Length of stay in the intensive care unit and in the hospital","definition_or_measurement_approach":"Measured as duration (days) of ICU and overall hospital stay."}
  • {"endpoint_text":"- Vital status at day 28 and day 90","definition_or_measurement_approach":"Recorded survival status at day 28 and day 90 post-inclusion."}
  • {"endpoint_text":"- Opioid use at D90","definition_or_measurement_approach":"Assessment of opioid consumption/use at day 90."}

Recruitment

Planned Sample Size
50
Recruitment Window Months
43
Consent Approach
Informed consent may be signed by the patient or by the patient's trusted person, legal representative, family member, curator or tutor; emergency consent procedure is allowed. Subject information and ICF documents are available for patient and proche (French language documents present). Vulnerable population selection noted in trial record.

Geography

Total Number Of Sites
1
Total Number Of Participants
50

France

Earliest CTIS Part Ii Submission Date
26-09-2024
Latest Decision Or Authorization Date
19-11-2025
Processing Time Days
419
Number Of Sites
1
Number Of Participants
50

Sites

Site Name
Centre Hospitalier Universitaire De Nimes
Department Name
+33466683050
Principal Investigator Name
Rémy WIDEHEM
Principal Investigator Email
remy.widehem@chu-nimes.fr
Contact Person Name
Rémy WIDEHEM
Contact Person Email
remy.widehem@chu-nimes.fr
Number Of Participants
50

Sponsor

Primary sponsor

Full Name
Centre Hospitalier Universitaire De Nimes
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
NEFOPAM VIATRIS 20 mg/2 ml, solution injectable
Active Substance
NEFOPAM HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
Authorised
Starting Dose
Initial dose of 20mg nefopam IVL over 30 minutes (per arm description)
Dose Levels
Protocol daily dose described as 400 mg (per arm description); product max daily dose listed as 120 mg in product dictionary
Frequency
Daily (as per protocol experimental schedule)
Maximum Dose
120 mg (product maxDailyDoseAmount) / protocol describes daily 400 mg
Investigational Product Name
TRAMADOL ARROW 100 mg/2 mL, solution injectable/pour perfusion
Active Substance
TRAMADOL HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
Authorised
Starting Dose
Initial dose of 50mg tramadol IVL over 30 minutes (per arm description)
Dose Levels
Protocol daily dose described as 120 mg (per arm description); product max daily dose listed as 450 mg
Frequency
Daily (as per protocol experimental schedule)
Maximum Dose
450 mg (product maxDailyDoseAmount)
Investigational Product Name
PARACETAMOL B BRAUN 10 mg/ml, solution pour perfusion
Active Substance
PARACETAMOL
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
Authorised
Dose Levels
Product max daily dose 3 g (product dictionary)
Frequency
As per conventional strategy dosing schedule
Maximum Dose
3 g (product maxDailyDoseAmount)
Investigational Product Name
ULTIVA 5 mg, poudre pour solution injectable ou pour perfusion
Active Substance
REMIFENTANIL HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous infusion
Authorisation Status
Authorised
Dose Levels
Product lists dosing in mg/kg/h; product maxDailyDoseAmount 0.03 mg/kg/h
Frequency
Continuous infusion adjusted in stages per protocol
Maximum Dose
0.03 mg/kg/h (product maxDailyDoseAmount)
Investigational Product Name
KETAMINE RENAUDIN 50 mg/ml, solution injectable
Active Substance
KETAMINE HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
Authorised
Dose Levels
Product maxDailyDoseAmount 0.15 mg/kg/h (product dictionary shows doseUom mg/kg/h and maxDailyDoseAmount 0.15)
Maximum Dose
0.15 mg/kg/h (product maxDailyDoseAmount)
Investigational Product Name
CHLORURE DE SODIUM 0,9 % AGUETTANT, solution pour perfusion
Active Substance
SODIUM CHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS USE
Route
Intravenous
Authorisation Status
Authorised
Dose Levels
Used as placebo; product maxDailyDoseAmount 600 ml
Frequency
As per blinded administration schedule
Maximum Dose
600 ml/day (product maxDailyDoseAmount)
Combination Treatment
Yes

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