Clinical trial NCT04658173: Efficacy and Safety Profile of Remimazolam-alfentanil Combination for ERCP Sedation
Official title: A Randomized, Controlled Trial to Compare the Efficacy and Safety Profile of a Remimazolam-alfentanil Combination With a Propofol-alfentanil Combination for ERCP
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Anesthesia
Keywords: ERCP
Propofol
Remimazolam
Alfentanil
Lead sponsor: Tianjin Nankai Hospital
Sponsor class: OTHER
First posted: 2020-12-08
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Moderate to deep levels of sedation and analgesia are required for ERCP. Propofol-based sedation is simple, easy to use, and effective, but is not without cardiovascular and respiratory adverse effects. The combination of remimazolam and alfentanil has shown promising results for sedation in other similar scenarios. The aim of this study was to compare the efficacy and safety of a standard propofol-alfentanil regimen with a remimazolam-alfentanil combination.

Detailed description: What is already known about this topic is that propofol-based sedation techniques are effective for ERCP procedures but are not without cardiovascular and respiratory adverse effects.

1. Title:A randomized, controlled trial to compare the efficacy and safety profile of a remimazolam-alfentanil combination with a propofol-alfentanil combination for ERCP.
2. Research center: Single center.
3. The Design of the study: Randomized, double-blind, controlled study.
4. The population of the study: Age is between 18 and 85 years; ASA I-III levels; Patients undergone elective ERCP surgery, non-intubation patients;
5. Sample size: Based on Akhondzadeh R et al. research, propofol based sedation resulted in 43% patients present oxygen desaturation, and assuming a 15% reduction in hypoxic events in remimazolam group. From this, we have estimated that oxygen desaturation rate will be 43% in the propofol group and 28 % in the remimazolam group. We have estimated that, with a sample size of 207 patients, the study will have 80% power to detect a significant difference using the log-rank test. We have estimated that the rate of dropout or withdrawal will be approximately 20%, and thus we plan to enroll 259 patients each group
6. Interventions: Group remimazolam-alfentanil combination received 10 µg/kg alfentanil and 0.3mg/kg remimazolam over 30 seconds, followed by an infusion of remimazolam at 0.2 to 1 mg/kg/hr and alfentanil at 0 to 1ug/kg/min. In case of the sudden patient movement, and difficulty in maneuvering the endoscope, remimazolam 0.1mg/kg was used in the form of bolus, as rescue drugs, and alfentanil 5ug/kg when additional analgesia is needed.

   Group propofol-alfentanil combination received 10 µg/kg alfentanil and 1.5 to 2 mg/kg propofol over 30 seconds followed by an infusion of propofol at 2 to 6mg/kg/hr and alfentanil at 0 to 1ug/kg/min. In case of the sudden patient movement, and difficulty in maneuvering the endoscope,propofol 0.5mg/kg was used in the form of bolus, as rescue drugs, and alfentanil 5ug/kg when additional analgesia is needed.
7. Outcome： Primary outcome： The occurrence of hypoxia, defined by any event of SpO2 (oxygen saturation measured by pulse oximetry) \< 90% of any duration.

   Secondary outcome： Number of events of hypoxia, defined as desaturation \< 90%. The mean number of events during the procedure will be compared between the two groups.

   Lowest recorded SpO2 during the procedure. Requirement of minor airway manoeuvres: jaw lift/jaw thrust, nasopharyngeal airway insertion.

   Requirement of major airway manoeuvres: bag mask ventilation, endotracheal intubation.

   Total alfentanyl dose. The mean values (the doses in micrograms) during the procedure will be compared between the two groups.

   Requirement of antispasmodic agent. Proportion of patients requiring this medication will be compared between the two groups.

   Endoscope re-insertion rate. Rescued sedation: drugs dose. Total duration of procedure. Duration under sedation/anaesthesia. Successful completion of the procedure: Yes/No. Proportion of patients fulfilling this criterion will be compared between the two groups.

   Sensation of abdominal bloating: Y/N. Proportion of patients experiencing this adverse event will be compared between the two groups.

   Patients' satisfaction score on leaving recovery: 5 points numerical rating scale: Very satisfied (5), somewhat satisfied (4), neither satisfied nor dissatisfied (3), somewhat dissatisfied (2), very dissatisfied (1). Proportion of patients at a particular threshold will be compared between the two groups.

   The endoscopist assessed the ease of performing at the end of the procedure as I-satisfactory, II-difficult or III-impossible.

   QOR-15. Recovery time :The time to recovery based on Modified Aldrete score was noted every 5 minutes, starting from the time of endoscope removal . A score of 9 was considered as recovery and the patient was discharged to the ward.The estimated duration of the study:2-3 years.

   If the procure is expected more than 1 hour, the arterial blood gas (ABG) will be detected before and after the ERCP, and the serum Aβ1-40 will be also determined by the commercial kits.
8. Adverse events:

   Incidence of hypertention, hypotension，tachycardia , bradycardia，nausea，vomiting, POD, Sensation of abdominal bloating, The dosage of urapidil, ephedrine, atropine and esmolol during the observation period
9. Safety consideration: ECG, HR, MAP, respiratory rate was monitored.
10. Statistical analysis Mean and standard deviation values will be estimated for continuous outcomes while frequency and percentage will be computed for binary outcomes. 95% confidence intervals around the point estimate will be calculated where appropriate for the primary and secondary outcomes. Descriptive statistics will be used to present the results. P \< 0.05 will be considered significant. Analyses will be intention-to-treat from randomisation. All randomised cases will be included in the analyses, regardless of missing data. As the data capture is only limited to a few hours after the intervention and the investigators are directly involved in the conduct of the study, we anticipate very few missing data. A subgroup analyses will be attempted (if feasible)

Eligibility criteria: Inclusion Criteria:

* Age is between 18 and 85 years
* ASA I-III levels;
* Patients undergone elective ERCP surgery, non-intubation patients;

Exclusion Criteria:

* Chronic pain with long-term use of analgesics, psychotropic substances (including opioids, NSAIDs, sedatives, antidepressants), alcohol abusers, with known drug allergy;
* BMI\<18 or BMI\>30;
* Abnormal renal function ;
* Previous abnormal surgical anesthesia recovery history;
* Hypertension or systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 95 mmHg when the patient admission to the operating room
* Sedatives, analgesics and antipruritic drugs were used 24 hours before operation;
* Expected difficult intubation ;
* Opioids allergy history;
* Take monoamine oxidase inhibitor or antidepressant within 15 days;
* Pregnant or parturient women;
* Involved in other drug trials within three months;
* Patients who can not communicate well with the researcher

Primary outcomes:
measure: The number of hypoxia
timeFrame: 1 day
Secondary outcomes:
measure: Number of events of hypoxia, defined as desaturation < 90%.
timeFrame: 1 day
measure: Lowest recorded SpO2 during the procedure
timeFrame: 1 day
measure: the number of requirement for minor airway manoeuvres
timeFrame: 1 day
measure: the number of requirement for major airway manoeuvres
timeFrame: 1 day
measure: Total alfentanyl dose
timeFrame: 1 day
measure: Requirement of antispasmodic agent
timeFrame: 1 day
measure: Endoscope re-insertion rate
timeFrame: 1 day
measure: Rescued sedation:
timeFrame: 1 day
measure: Total duration of procedure
timeFrame: 1 day
measure: Duration under sedation/anaesthesia
timeFrame: 1day
measure: Successful completion of the procedure
timeFrame: 1 day
measure: Sensation of abdominal bloating
timeFrame: 1-3 days
measure: Patients' satisfaction score on leaving recovery
timeFrame: 1-3 days
measure: The endoscopist assessed the ease of performing at the end of the procedure as I-satisfactory, II-difficult or III-impossible
timeFrame: 1 days
measure: quality of recovery score-15
timeFrame: 1-3 days
measure: Recovery time
timeFrame: 1 day
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Nankai Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin NanKai hospital
state: Tianjin
Study officials:
affiliation: Tianjin Nankai Hospital
name: Jianbo Yu, MD
role: PRINCIPAL_INVESTIGATOR
References:
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