Clinical trial NCT04315935: Comparison of Analgesic Effect and Prognosis of Butorphanol and Fentanyl in Patients With Mechanical Ventilation
Official title: Comparison of Analgesic Effect and Prognosis of Butorphanol and Fentanyl in Patients With Mechanical Ventilation: a Prospective, Randomized, Multicenter Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Analgesia
Lead sponsor: Jiangsu Hengrui Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-20
Enrollment: 355
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: ICU patients often in a strong stress environment. Various invasive procedures such as wound dressing change, sputum suction,Pull out the thoracic duct etc. At the same time, the diseases and environmental factors caused patients anxiety, pain, delirium and even a series of pathophysiological changes which harm life and safety. Fentanyl is an analgesic that acts on central μ receptors, clinical practice had found that fentanyl could exert analgesic effects, while it maybe affect patients' hemodynamics, breathing, and nervous system, which caused hypotension, bradycardia, respiratory depression, delirium and other adverse drug reactions. These reactions prolonged the mechanical ventilation time and duration time of patients in hospital, which impact the treatment effect and prognosis of patients. Butorphanol tartrate is a new type of opioid receptor agonist and antagonist, which can stimulate the κ receptor, and also certain stimulated and antagonised effects on the μ receptor. It can be used for analgesia and sedation in patients of ICU. Previous studies shown that butorphanol can inhibit the inflammatory response and effect myocardial protective. The analgesic effect of butorphanol were equivalent to fentanyl in patients of ICU, and the incidence of nausea and vomiting in participants with butorphanol less than fentanyl. Therefore, the investigators speculate that the analgesia of butorphanol in ICU patients may unexpected effects. However, butorphanol and fentanyl on the analgesic effect and prognosis of patients with mechanical ventilation in ICU are lacking currently, and the investigators no corresponding multi-center clinical study at home and abroad. The research compare to the analgesic effect of butorphanol and fentanyl in critically ill patients with mechanical ventilation. Effects of butorphanol and fentanyl on mechanical ventilation duration, sedation depth, duration time of patients in hospital, complications and mortality in patients with mechanical ventilation. To analyze the high-risk factors affecting the prognosis of patients with mechanical ventilation in ICU. Found more treatment measures for analgesia of patients with mechanical ventilation in ICU.

Detailed description: For enrolled patients, the investigators required that inclusion criteria were informed consent signed.The exclusion criteria were described in detail in the CRF standard. The recruitment of patients into the group were conducted in each sub-center according to Inclusion criteria. After the inclusion of patients will registed relevant information according to the basic data table of patients, disease information table and baseline data table, and then randomly divide the patients into groups by special statistician (CRA/CRO).The relevant data in the clinical study were collected by specialized nurses or data recording team.The daily statistical results need to record and dated by statisticians in order to track the authenticity and reliability of the data. The statistician should communicate with the doctor in charge about the situation out the trial plan during the study. If there is any change in the test plan, it is necessary to mark the measures and reasons for the change in detail, and sign the signature and date of the statistician and the responsible doctor in the statistical table of the day. The recorded data of the study should be updated with electronic documents. Statistical recorder of data need to make weekly summary, summarize and submit the statistical data of last month at each sub-research center at the beginning of each month, then the lead hospital will summarize and analyze the data.As for the problems beyond the experimental schemes in the research process, each branch center needs to discuss with the lead center. Every three months, progress meetings will be held to discuss various problems in clinical research and to unify standards for related problems to ensure the smooth progress of clinical research and the true reliability of experimental results. SAS 9.4 software was used for statistical analysis. The analysis content included subject distribution description, baseline index balance analysis, efficacy analysis and safety analysis.The significance level of the statistical test was α=0.05. In the safety analysis, the incidence of adverse events and adverse reactions was calculated and the specific conditions of all subjects with adverse events were listed. The list of vital signs and normal abnormalities in laboratory examination before and after medication was described, and the specific conditions of subjects with abnormal conditions before and after treatment and abnormal conditions before and after treatment were listed in detail.After completing the statistical analysis, the statistical analyst should record the data and submit it to the main researcher of the experiment to fill with the general analysis report. All cases, whether observation or shedding, should be completed in accordance with the requirements of "case report form". The case report form were copied three copies with without carbon copy. After the completion of data entry, the sponsor (the first copy), the unit in charge of the clinical research (the second copy) and the clinical research unit (the third copy) shall file it respectively.

Eligibility criteria: Inclusion Criteria:

1. aged \>= 18 years, 18kg / m2 \< BMI \< 30 kg / m2;
2. patients with invasive mechanical ventilation (refer to the clinical application guide of mechanical ventilation \[2006\];
3. the expected ventilation time was \>= 24h, and the ventilation time was \< 48h;
4. sign the informed consent voluntarily and participate in the research. -

Exclusion Criteria:

1. known allergy to any study drug;
2. for chronic pain of grade 3 or above in the World Health Organization, strong opioids, such as morphine, are often used. Recently, opioids are used for analgesia through spinal cord catheter, epidural or any other regional block;
3. the American Society of anesthesiologists (ASA) classified the fifth grade patients (on the verge of death);
4. nerve injury or brain organic pathological changes;
5. participate in clinical research in the past 30 days;
6. pregnancy or lactation;
7. the researcher thinks it is not suitable to participate in the clinical trial.

Primary outcomes:
measure: Analgesic score,
timeFrame: Maintain target analgesia score (CPOT<3) from 100% time to 80% time
measure: sedative score
timeFrame: Maintain target analgesia score (CPOT<3) from 100% time to 80% time
measure: Total dosage of butorphanol， fentanyl，propofol;
timeFrame: Maintain target analgesia score (CPOT<3) from 100% time to 80% time
Secondary outcomes:
measure: Major indicators affecting the prognosis of patients in ICU
timeFrame: From day 1 to day 30
Other outcomes:
measure: Incidence of adverse reactions
timeFrame: From day 1 to day 30
Locations:
city: Hebei
country: China
facility: Hebei People's Hospital
state: Hebei
Study officials:
affiliation: Hebei People's Hospital
name: Quansheng Q Du, doctor
role: PRINCIPAL_INVESTIGATOR
References: