Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Adjuvant Continuous Infusion of Nefopam Versus Standard of Care in Mechanically Ventilated Critically Ill Patients: Randomized Double-blind Controlled Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05071352
Recruitment Status : Not yet recruiting
First Posted : October 8, 2021
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
Mohammed Gamal Abdelraouf Amer, Cairo University

Tracking Information
First Submitted Date  ICMJE September 4, 2021
First Posted Date  ICMJE October 8, 2021
Last Update Posted Date October 8, 2021
Estimated Study Start Date  ICMJE October 2021
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2021)
Cumulative dose of fentanyl [ Time Frame: First 24 hour after randomization. ]
To compare the cumulative dose of fentanyl
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2021)
  • Richmond Agitation and Sedation Score (RASS) [ Time Frame: First 24 hours after randomization. ]
    To compare number of patients are in RASS score goal. RASS score minumum -5 (unarousable), maximun +4 (Combative). Goal RASS score from -1 (drowsy) to 0 (alert and calm).
  • pain score [ Time Frame: First 24 hours after randomization. ]
    To compare number of patients are in Pain score goal. If patient able to communicate we use the 0-10 numeric rating scale in a visual format (NRS-V), 0 indicate no pain and 10 indicate the worst pain imaginable. For patient unable to communicate we use Critical care pain observation tool (CPOT) score, a score ≥3 indicate significant pain.
  • Duration of mechanical ventilation (MV) [ Time Frame: The number of calendar days from intubation date to extubation date, until ICU discharge, death, or 28 days post-randomization, whichever comes first. ]
    To assess whether nefopam can help to shorten the of being mechanically ventilated.
  • vasopressor requirements [ Time Frame: First 24 hours after randomization. ]
    To compare vasopressors requirement
  • Hemodynamics [ Time Frame: First 24 hours after randomization. ]
    changes in Mean Arterial Pressure (MAP) mmHg
  • Hemodynamics [ Time Frame: First 24 hours after randomization. ]
    changes in Heart Rate (HR) beats/minute.
  • ICU length of stay (LOS) [ Time Frame: From randomization to ICU discharge date ]
    To compare ICU LOS
  • Tracheostomy [ Time Frame: 28 days post-randomization ]
    Tracheostomy rate
  • Unplanned extubation (self-extubation) [ Time Frame: 28 days post-randomization ]
    Unplanned extubation date rate
  • Re-intubation [ Time Frame: 28 days post-randomization ]
    Re-intubation rate
  • Incidence of delirium [ Time Frame: 24 hour after randomization ]
    Rate of positive confusion assessment method for the ICU (CAM-ICU) score
  • Use of antipsychotics [ Time Frame: 24 hour after randomization ]
    Rate of using antipsychotics for confirmed ICU-acquired delirium
  • Use of physical restraint [ Time Frame: 24 hour after randomization ]
    Use of physical restraint
  • Mortality rate at the time of hospital discharge or 28 days after randomization, whichever comes first. [ Time Frame: 28 days after randomization ]
    Mortality rate at the time of hospital discharge or 28 days after randomization, whichever comes first.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Continuous Infusion of Nefopam Versus Standard of Care in Mechanically Ventilated Critically Ill Patients: Randomized Double-blind Controlled Study
Official Title  ICMJE Adjuvant Continuous Infusion of Nefopam Versus Standard of Care in Mechanically Ventilated Critically Ill Patients: Randomized Double-blind Controlled Study
Brief Summary The aim of this prospective, randomized, active control, double blinded study is to assess the effect and safety of continuous infusion nefopam in mechanically ventilated ICU patients compared to standard of care. It is being hypothesized that continuous infusion nefopam will reduce opioid use with acceptable safety profile compared to standard of care.
Detailed Description

Pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage". Critically ill patients experience pain at rest and during standard caring procedures. Arterial catheter insertion, chest tube removal, wound drain removal, wound care, and turning are associated with the greatest increased pain intensity. Pain have short and long-term sequelae on critically ill patients. Short-term sequelae include impaired tissue oxygenation, impaired wound healing, and impaired immune functions. Long-term sequelae include chronic pain, Post-traumatic stress disorder (PTSD) symptoms, and a lower health-related quality of life.

The gold standard for pain assessment is patient's self-report of pain. For critically ill able to self-report pain the 0-10 numeric rating scale in a visual format (NRS-V) is the best to use. Unfortunately, a lot of critically ill patients are unable to communicate and self-report pain. So, using behavioral pain scales are suitable in this type of patients, Critical care pain observation tool (CPOT) demonstrates validity and reliability for monitoring pain in critical ill adult patient who are unable to self-report pain and in whom behaviors are observable. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption (PADIS) guideline panel suggests "using an assessment-driven, protocol-based, stepwise approach for pain and sedation management in critically ill adults" and state as a good practice statement "critically ill adults should be regularly assessed for delirium using a valid tool".

Opioids are a cornerstone in the management of pain in critically ill patient, but have a lot of negative consequences including constipation, urinary retention, bronchospasm, over-sedation, respiratory depression, hypotension, nausea, truncal rigidity, delirium, and immunosuppression. Also, they contribute to vasodilatation and hypotension which lead to increased resuscitation fluids volume in critically ill patient.

"Multi-modal analgesia" also known as "balanced analgesia" approach via using non-opioids adjuvant or in replacement of opioids to target different pain pathways leads to optimizing analgesia and reducing opioids consumption. In France, the second most prescribed non-opioids in mechanically ventilated intensive care unit (ICU) patient is nefopam. Nefopam is a non-opioid, non-steroidal centrally acting analgesic, although the exact mechanism of action poorly understood, analgesic activity is thought to be via inhibiting dopamine, norepinephrine, serotonin reuptake. Nefopam was non-inferior to fentanyl for pain control in patients undergoing elective cardiac surgery without increase in adverse effects. Nefopam has a fentanyl sparing effect up to 50% in patients underwent laparoscopic total hysterectomy.

The 2018 PADIS guideline panel made a conditional recommendation for using "nefopam (if feasible) either as an adjunct or replacement for an opioid to reduce opioid use and their safety concerns for pain management in critically ill adults".

Therefore, the aim of this prospective, randomized, active control, double blinded study is to assess the effect and safety of continuous infusion nefopam in mechanically ventilated ICU patients compared to standard of care. It is being hypothesized that continuous infusion nefopam will reduce opioid use with acceptable safety profile compared to standard of care.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Analgesia
  • Critical Illness
  • Mechanical Ventilation
  • Sedation
Intervention  ICMJE
  • Drug: Nefopam
    Nefopam will be administered as an initial dose of 20 mg IV dose infused over 15 minutes then, as continuous infusion of 5 mg/hr for 24 hours.
    Other Name: Acupan
  • Drug: Standard of care in the ICU for assessment and management of pain, sedation, and delirium.
    In our protocol we use analgiosedation approach (an opioid is used before a sedative to reach the sedation goal), targeting light sedation using richmond agitation sedation scale (RASS) score -1 to 0, and assess delirium using confusion assessment method for the ICU (CAM-ICU).
    Other Name: Standard of care
Study Arms  ICMJE
  • Experimental: Nefopam group

    Adjunct continuous infusion of nefopam plus standard of care in ICU for assessment and management of pain, sedation, and delirium.

    Nefopam will be administered as an initial dose of 20 mg IV dose infused over 15 minutes then, as continuous infusion of 5 mg/hr for 24 hours.

    Interventions:
    • Drug: Nefopam
    • Drug: Standard of care in the ICU for assessment and management of pain, sedation, and delirium.
  • Placebo Comparator: Control group
    Standard of care in the ICU for assessment and management of pain, sedation, and delirium.
    Intervention: Drug: Standard of care in the ICU for assessment and management of pain, sedation, and delirium.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 5, 2021)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult patients >18 years on mechanical ventilation and expected to need ventilatory support for the next 24 hours.
  2. Candidate for sedation and analgesia protocol

Exclusion Criteria:

  1. Pregnant and/or lactating woman.
  2. Has been intubated for duration longer than 12 hours in an intensive care unit.
  3. Proven or suspected acute primary brain lesion such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury.
  4. Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness.
  5. Admission as a consequence of a suspected or proven drug overdose
  6. Mean arterial pressure (MAP) < 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomization.
  7. Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient or substitute decision maker is not committed to active treatment.
  8. Patients with severe hepatic impairment (Child-Pugh class C) or end stage renal disease (ESRD) (creatinine clearance < 30 ml/min or on chronic hemodialysis) due to altered pharmacokinetics [20].
  9. Need for deep sedation such as administration of neuromuscular blockers.
  10. Convulsions or previous history of convulsions.
  11. Risk of urinary retention linked to uretroprostatic disorders.
  12. Risk of acute angle glaucoma.
  13. Known intolerance of or hypersensitivity to study medications or constituents.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mohammed Gamal Abdelraouf Amer, Pharm D 00201025556853 m.abdelraouf@std.pharma.cu.edu.eg
Listed Location Countries  ICMJE Egypt
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05071352
Other Study ID Numbers  ICMJE Nefopam
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mohammed Gamal Abdelraouf Amer, Cairo University
Study Sponsor  ICMJE Cairo University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mohammed Gamal Abdelraouf Amer, Pharm D Cairo University Hospitals
PRS Account Cairo University
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP