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

February 6, 2023 updated by: Mohammed Gamal Abdelraouf Amer, Cairo University
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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt
        • Recruiting
        • Cairo University Hospitals (Kasr Alainy)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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 Names:
  • 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 Names:
  • Standard of care
PLACEBO_COMPARATOR: Control group
Standard of care in the ICU for assessment and management of pain, sedation, and delirium.
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 Names:
  • Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative dose of fentanyl
Time Frame: First 24 hour after randomization.
To compare the cumulative dose of fentanyl
First 24 hour after randomization.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
First 24 hours after randomization.
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.
First 24 hours after randomization.
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.
The number of calendar days from intubation date to extubation date, until ICU discharge, death, or 28 days post-randomization, whichever comes first.
vasopressor requirements
Time Frame: First 24 hours after randomization.
To compare vasopressors requirement
First 24 hours after randomization.
Hemodynamics
Time Frame: First 24 hours after randomization.
changes in Mean Arterial Pressure (MAP) mmHg
First 24 hours after randomization.
Hemodynamics
Time Frame: First 24 hours after randomization.
changes in Heart Rate (HR) beats/minute.
First 24 hours after randomization.
ICU length of stay (LOS)
Time Frame: From randomization to ICU discharge date
To compare ICU LOS
From randomization to ICU discharge date
Tracheostomy
Time Frame: 28 days post-randomization
Tracheostomy rate
28 days post-randomization
Unplanned extubation (self-extubation)
Time Frame: 28 days post-randomization
Unplanned extubation date rate
28 days post-randomization
Re-intubation
Time Frame: 28 days post-randomization
Re-intubation rate
28 days post-randomization
Incidence of delirium
Time Frame: 24 hour after randomization
Rate of positive confusion assessment method for the ICU (CAM-ICU) score
24 hour after randomization
Use of antipsychotics
Time Frame: 24 hour after randomization
Rate of using antipsychotics for confirmed ICU-acquired delirium
24 hour after randomization
Use of physical restraint
Time Frame: 24 hour after randomization
Use of physical restraint
24 hour after randomization
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.
28 days after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 1, 2021

Primary Completion (ANTICIPATED)

October 1, 2023

Study Completion (ANTICIPATED)

October 1, 2023

Study Registration Dates

First Submitted

September 4, 2021

First Submitted That Met QC Criteria

October 5, 2021

First Posted (ACTUAL)

October 8, 2021

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 6, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Nefopam

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Critical Illness

Clinical Trials on Nefopam

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mexico

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe