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Etomidate vs. Midazolam for Sedation During ERCP

Sponsor
Cheju Halla General Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT02027311
Collaborator
(none)
63
Enrollment
1
Location
2
Arms
4
Duration (Months)
15.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recently up-coming drug, etomidate which is a modulator of GABA(gamma-Aminobutyric acid)-A receptor has been known that it maintains the appropriate sedative levels and affects little effects on respiratory system.

The investigators are now trying to investigate that etomidate with meperidine combination regimen is superior to the midazolam with meperidine more effective and less harm on sedation during the ERCP procedure.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

ERCP (Endoscopic retrograde cholangiopancreatogram) is an uncomfortable and time-consuming procedure compared to other endoscopic procedures. Most ERCP procedure had been performed in sedation using tranquilizers and pain-killers.

Until recently, midazolam and opioid combination regimen recognized as a standard therapy is widely used, but the sedative effect is insufficient and intermittent paradoxical reaction has been questioned. Another drug, such as propofol, has been known that the sedative effect is superior one of the midazolam but disappointed due to narrow therapeutic range of respiratory distress and absence of antagonist. Meanwhile, recently up-coming drug, etomidate which is a modulator of GABA-A receptor has been known that it maintains the appropriate sedative levels and affects little effects on respiratory system.

For these advantages, this short acting sedative drug has been widely used in the emergency room during minor operation and in the operation room for induction. However, research on the efficacy during ERCP was not yet published.

In this regards, the purpose of the investigators study is to prove the efficacy of etomidate for sedation and to establish new evidence based sedation guidelines during ERCP procedure.

Study Design

Study Type:
Interventional
Actual Enrollment :
63 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Etomidate With Meperidine vs Midazolam With Meperidine for Sedation During Endodscopic Retrograde Cholangiopancreatogram (ERCP)
Study Start Date :
Apr 1, 2013
Actual Primary Completion Date :
Aug 1, 2013
Actual Study Completion Date :
Aug 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Etomidate

This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.

Drug: Etomidate
This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.
Other Names:
  • Etomidate lipro IV

    • Drug: Meperidine
    Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus.
    Other Names:
  • Pethidine

    		•
    Experimental: Midazolam

    This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.

    Drug: Midazolam
    This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.

    Drug: Meperidine
    Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus.
    Other Names:
  • Pethidine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Intervention [Throughout the whole ERCP procedure]

      The frequency of intervention which was defined as any restraint of the patient's head, arms, or legs if they became agitated, or if patient movement was not controlled with verbal instruction from the endoscopist during the whole intraoperative phases.

    Secondary Outcome Measures

    1. Event of Hypoxia [Every 5min in Preoperative, intraoperative phase and 15 min in Recovery phase]

      Hypoxia defined as peripheral blood oxygen saturation measured by pulse oxymeter < 90%

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • All patients who are scheduled diagnositic or therapeutic ERCP.

    • Age : more than 20 and less than 90 years old

    • ASA(American Society of Anesthesiologists) classificiation : I, II, III

    Exclusion Criteria:Patients following

    • Refuse to be enrolled

    • ASA American Society of Anesthesiologists)classification IV, V

    • Breast feeder

    • The mentally ill

    • Drug abuser

    • Hypersensitivity to sedative or opioids

    • Alcohol intoxication or dependency

    • Body mass index (BMI) 36kg/m2 or more

    • Unstable vital sign

    1. tachypnea, respiration rate more than 25/min or less than 10/min

    2. Oxygen saturation : 90% or less

    3. Systolic blood pressure : less than 90 mmHg or more than 180 mmHg

    4. Diastolic blood pressure : less than 50 mmHg or more than 100 mmHg

    5. Heart rate : more than 120 beat/min or less than 50 beat/min.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 1Digestive Disease Center and Department of Internal Medicine, Cheju Halla General Hospital Jeju-si Jeju Special Self-Governing Province Korea, Republic of 690-766

    Sponsors and Collaborators

    • Cheju Halla General Hospital

    Investigators

    • Study Chair: BYUNG HYO CHA, Dr., Cheju Halla General Hospital, Doreongno 65, Jeju-si Jeju Special Self-Governing Province, Korea 690-766

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Byung Hyo Cha, MD, Director of Endoscopy clinic, Digestive Disease Center, Department of Internal Medicine, Cheju Halla General Hospital
    ClinicalTrials.gov Identifier:
    NCT02027311
    Other Study ID Numbers:
    • ETOMI-1
    First Posted:
    Jan 6, 2014
    Last Update Posted:
    Jun 29, 2015
    Last Verified:
    Jun 1, 2015
    Keywords provided by Byung Hyo Cha, MD, Director of Endoscopy clinic, Digestive Disease Center, Department of Internal Medicine, Cheju Halla General Hospital
    Endoscopic Retrograde Cholangiopancreatography (ERCP)
    Conscious Sedation
    etomidate
    midazolam
    Additional relevant MeSH terms:
    Cholangiocarcinoma
    Pancreatitis
    Choledocholithiasis
    Midazolam
    Meperidine
    Etomidate

    Study Results

    Participant Flow

    Recruitment Details Eligibility was evaluated for all patients with a scheduled ERCP procedure in the Cheju Halla General Hospital during the study period from May 15 2013 to Aug 19 2013. Sample size estimated 26 of each groups for reject null hypothesis with probability (power) 0.8 and Type I error is 0.05.
    Pre-assignment Detail 68 patients were enrolled and 35 were assigned in the MDZ group and 33 were in the ETM group. In ETM group, 1 case was dropped due to hypotension and 2 were desaturation. And 1 cases was dropped due to tachycardia and 1 were desaturation in MDZ group.
    Arm/Group Title Etomidate Midazolam
    Arm/Group Description This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Etomidate: This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus. This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Midazolam: This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus.
    Period Title: Overall Study
    STARTED 33 35
    COMPLETED 30 33
    NOT COMPLETED 3 2

    Baseline Characteristics

    Arm/Group Title Etomidate Midazolam Total
    Arm/Group Description This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Etomidate: This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus. This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Midazolam: This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus. Total of all reporting groups
    Overall Participants 30 33 63
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70.3
    (15.7)
    71.6
    (11.5)
    70.9
    (13.8)
    Sex: Female, Male (Count of Participants)
    Female
    16
    53.3%
    19
    57.6%
    35
    55.6%
    Male
    14
    46.7%
    14
    42.4%
    28
    44.4%
    Body Mass Index (kg/square of m.) (kg/square of m.) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/square of m.]
    23.7
    (3.5)
    22.6
    (4.31)
    23.1
    (3.9)
    Procedure Time (min) (min) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [min]
    27.6
    (14.9)
    32.8
    (13.4)
    30.4
    (14.2)

    Outcome Measures

    1. Primary Outcome
    Title Number of Intervention
    Description The frequency of intervention which was defined as any restraint of the patient's head, arms, or legs if they became agitated, or if patient movement was not controlled with verbal instruction from the endoscopist during the whole intraoperative phases.
    Time Frame Throughout the whole ERCP procedure

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Etomidate Midazolam
    Arm/Group Description This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Etomidate: This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus. This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Midazolam: This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus.
    Measure Participants 30 33
    Mean (Standard Deviation) [Number of intervention]
    1.9
    (3.1)
    7.5
    (6.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etomidate, Midazolam
    Comments If the true difference in the experimental and control means is 4, total 26 experimental subjects and 26 control subjects was required to reject the null hypothesis that the means of the primary outcome values of experimental and control groups are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.05
    Comments For two-sided tests, p < 0.05 was considered statistically significant.
    Method Regression, Logistic
    Comments Logistic regression model used to identify the factors related to the presence of intervention (frequency of intervention = 0, vs. ≥ 1).
    2. Secondary Outcome
    Title Event of Hypoxia
    Description Hypoxia defined as peripheral blood oxygen saturation measured by pulse oxymeter < 90%
    Time Frame Every 5min in Preoperative, intraoperative phase and 15 min in Recovery phase

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Midazolam Etomidate
    Arm/Group Description This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Midazolam: This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus. This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Etomidate: This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus.
    Measure Participants 33 30
    Number [Hypoxia events]
    19
    27
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Etomidate, Midazolam
    Comments All the continuous variables were compared using the Mann-Whitney U test and dichotomous categorical variables was used and the Pearson chi-square with Fisher exact test. We used the linear mixed model to compare the differences of paired data, such as mean values of RR, SpO2, MAP, HR, and RSS at different time points of the two different sedation groups. For two-sided tests, p < 0.05 was considered statistically significant.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments Logistic regression model were used in univariate and corrected multivariate analyses to identify the factors related to the primary outcome variables, such as, presence of intervention (frequency of intervention = 0, vs. ≥ 1).
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 11.09
    Confidence Interval (2-Sided) 95%
    2.41 to 50.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame BP, RR, HR, and SpO2 were monitored at 5-minute intervals after the baseline measurements until the termination of the ERCP. The baseline measurements were obtained at least 15 minutes before any medication was administered to patients.
    Adverse Event Reporting Description Additional probable side events, such as, paradoxic reaction in MDZ group, and myoclonus in ETM group were counted during the whole 3 phases of procedure.
    Arm/Group Title Etomidate Midazolam
    Arm/Group Description This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Etomidate: This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus. This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Midazolam: This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%. Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders > 80 years old were administered 25mg iv bolus.
    All Cause Mortality
    Etomidate Midazolam
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Etomidate Midazolam
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/30 (0%) 0/33 (0%)
    Other (Not Including Serious) Adverse Events
    Etomidate Midazolam
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/30 (0%) 0/33 (0%)

    Limitations/Caveats

    To standardize proper sedation level we used Ramsay Sedation Scale but this scale could be calculated subjectively. Double blindness was not applied strictly because of quite different pharmacodynamics of two experimental drugs.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Byung Hyo Cha, Director of ETOMI-1 study
    Organization Digestive Disease Center and Department of Internal Medicine, Cheju Halla General Hospital
    Phone +82-64-740-8050
    Email drhyo@hotmail.com
    Responsible Party:
    Byung Hyo Cha, MD, Director of Endoscopy clinic, Digestive Disease Center, Department of Internal Medicine, Cheju Halla General Hospital
    ClinicalTrials.gov Identifier:
    NCT02027311
    Other Study ID Numbers:
    • ETOMI-1
    First Posted:
    Jan 6, 2014
    Last Update Posted:
    Jun 29, 2015
    Last Verified:
    Jun 1, 2015