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Propofol vs. Midazolam-based Balanced Propofol for Nonanesthesiologist Moderate Sedation in Colonoscopy (MIDAPROP)

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. Read our disclaimer for details. Identifier: NCT01428882
Recruitment Status : Completed
First Posted : September 5, 2011
Results First Posted : May 25, 2016
Last Update Posted : May 25, 2016
Information provided by (Responsible Party):
Javier Molina-Infante, MD, Infante, Javier Molina, M.D.

Brief Summary:

Nonanesthesiologist administration of propofol for sedation is actually a field of growing interest for endoscopists, as demonstrated by recent American and European guidelines on this issue. Propofol is a hypnotic drug with rapid onset and offset of action. Used as a single agent, it is commonly titrated to deep sedation, whereas balanced propofol sedation (BPS), which combines propofol with small doses of a benzodiazepine and/or an opioid, can be successfully titrated to moderate sedation. However, nonanesthesiologists propofol administration remains controversial on account of the possibility of deep sedation/general anesthesia related adverse events. On the other hand, the use of longer elimination half-life drugs, such as opioids and benzodiazepines, may theoretically prolong sedation and recovery.

Up to date, no study has addressed a head-to-head comparison of both regimens administered by non-anesthesiologists and titrated to moderate sedation.

This study aims to evaluate the impact on propofol sedation of premedication with a fixed dose of midazolam (2 mg)2 minutes before propofol administration targeted to moderate sedation, in terms of depth of sedation, recovery times, safety and satisfaction.

The onset of sedative action of midazolam has been reported to be 1-2.5 minutes and the peak effect of midazolam occurs 8-12 minutes. Taking into account that colonoscopy usually lasts a minimum of 15-20 minutes, our hypothesis is that synergy between propofol and midazolam may increase the depth of sedation through the initial phases of the procedure, diminishing propofol requirements, but not prolonging significantly recovery times.

Condition or disease Intervention/treatment Phase
Procedural Sedation Drug: Midazolam Drug: Propofol Phase 4

Detailed Description:

Justification of the study:

Nonanesthesiologist administration of propofol is controversial owing to deep sedation concerns. One of the latest therapeutic innovations on this issue has been the development of balanced propofol sedation, which consists of adding low doses of opioids or benzodiazepins. Several studies have recently demonstrated that BPS allows successfully moderate sedation, maintains a reversible drug component, reduces the total dose of propofol even by more than 50% without increasing adverse events and maintains high levels of physician and patient satisfaction, even for advanced endoscopic procedure. However, recovery may be prolonged by using midazolam or meperidine as they have a longer elimination half-life than propofol has.

Up to date, nonanesthesiologist administration of propofol and BPS, using either midazolam or fentanyl, for outpatient colonoscopy have been compared in a single non-placebo controlled randomized trial (VanNatta and Rex, 2006). In this study, the authors obtained shorter recovery times with BPS compared to propofol alone, in contrast with the expected on account of pharmacokinetics. These results can be easily understood yet single-agent propofol was titrated to deep sedation, whereas BPS was titrated to moderate sedation.

Therefore, it is necessary to make a randomized, double-blinded, placebo-controlled trial to directly compare both sedation regimens targeted to a similar moderate level of sedation. The results of this study will conclude which should be the first line treatment for moderate sedation in colonoscopy, providing further insight in drug synergy and its impact on the depth of sedation and recovery times

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 135 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Phase 4, Prospective, Randomized, Double-blinded, Placebo-controlled Study Comparing Propofol vs. Midazolam Plus Propofol for Nonanesthesiologist Targeted Moderate Sedation in Outpatient Colonoscopy
Study Start Date : June 2011
Actual Primary Completion Date : October 2011
Actual Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Colonoscopy

Arm Intervention/treatment
Active Comparator: Midazolam balanced propofol sedation
2 mg midazolam in 2 ml saline midazolam followed by continuous propofol iv infusion
Drug: Midazolam
Midazolam (5 mg/5 mL) 2 mg before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level
Other Name: Not necessary

Placebo Comparator: Single-agent propofol sedation
2 ml saline followed by continuous propofol iv infusion
Drug: Propofol
Placebo (normal saline 2 ml) before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level
Other Name: Not necessary

Primary Outcome Measures :
  1. Level of Sedation Throughout the Entire Procedure [ Time Frame: Up to 1 hour after introduction of the colonoscope ]
    Assessment every two minutes of the level of sedation during the endoscopic procedure, rating it as minimal, moderate or deep.

Secondary Outcome Measures :
  1. Duration of Recovery After the Endoscopic Procedure [ Time Frame: Up to 1 hour after colonoscopy ]

    After completion of the procedure, the patient stood in the examination room monitored continuously by a nurse. When patients responded to normal verbal command, they were asked to sit up and were offered a drink. This was considered the early recovery time.

    If they were able to stand unassisted by the bed and had stable hemodynamics parameters (saturation>90 % on room air and blood pressure and heart rate within 20 % of baseline), they were transferred to a locker room accompanied by a relative. The discharge criteria included ability to stand unassisted and tolerate clear liquids once dressed. Once a patient met discharge criteria, they were allowed to leave at their own discretion

  2. Rate of Sedation-related Complications During the Procedure and the Recovery Phases [ Time Frame: Up to two hours, including colonoscopy performance and recovery period ]
    The following events were considered complications of procedural sedation: a decline in oxygen saturation to less than 85 % longer than 30 s after increasing the oxygen flow rate to 5 L/min and transient propofol interruption, a heart rate less than 40 beats per minute and blood pressure less than 80/50 mmHg. Major complications were defined as need for mechanical ventilation or any cardiorespiratory event requiring anaesthesiologist assistance.

  3. Rate of Patients and Physician Satisfaction With Sedation [ Time Frame: Up to 1 hour after colonoscopy for endoscopists and up to 48 hours for patients ]

    Endoscopists and patients rated their satisfaction with sedation in a 10-cm visual analogue scale after discharge.The patients were contacted 24-48 h after the procedure to answer a questionnaire regarding if they remembered scope insertion or scope removal and willingness to repeat it with a similar protocol and rated their satisfaction and pain perception from 0 to 10. This phone survey was done by the nurse specifically making the measurements in the endoscopy room, who was blinded to the sedation regimen.

    For the interpretation of results of the 0-10 point numerical scale, 0 stands for 'extremely dissatisfied with sedation level during the endoscopic procedure', whereas 10 stands for 'extremely satisfied with sedation level during the endoscopic procedure".

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • All patients undergoing elective outpatient colonoscopy

Exclusion Criteria:

  • Age less than 18 years
  • Allergy to propofol, soybeans, eggs or midazolam
  • Chronic intake of benzodiazepines
  • History of colorectal surgery
  • ASA class IV, short and tick neck, difficult intubation due to inability to open the mouth widely
  • Pregnancy
  • Refusal, inability or unwillingness to give written consent
  • Patients scheduled for advanced therapeutic colonoscopy or for more than one endoscopic procedure

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01428882

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Hospital San Pedro de Alcantara
Caceres, Spain, 10003
Sponsors and Collaborators
Infante, Javier Molina, M.D.
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Principal Investigator: Javier Molina-Infante, MD Hospital San Pedro de Alcantara, Caceres, Spain

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Javier Molina-Infante, MD, Medical Doctor, Infante, Javier Molina, M.D. Identifier: NCT01428882    
Other Study ID Numbers: MIDP11
First Posted: September 5, 2011    Key Record Dates
Results First Posted: May 25, 2016
Last Update Posted: May 25, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by Javier Molina-Infante, MD, Infante, Javier Molina, M.D.:
Moderate sedation
Deep sedation
Additional relevant MeSH terms:
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Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action