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

April 16, 2016 updated by: Javier Molina-Infante, MD, Infante, Javier Molina, M.D.

Phase 4, Prospective, Randomized, Double-blinded, Placebo-controlled Study Comparing Propofol vs. Midazolam Plus Propofol for Nonanesthesiologist Targeted Moderate Sedation in Outpatient Colonoscopy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

135

Phase

  • Phase 4

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

  • Spain
      • Caceres, Spain, 10003
        • Hospital San Pedro de Alcantara

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:

  • 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

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 Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Not necessary

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 1 hour after introduction of the colonoscope

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 1 hour after colonoscopy
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.
Up to two hours, including colonoscopy performance and recovery period
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".
Up to 1 hour after colonoscopy for endoscopists and up to 48 hours for patients

Collaborators and Investigators

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

Sponsor

Infante, Javier Molina, M.D.

Investigators

  • Principal Investigator: Javier Molina-Infante, MD, Hospital San Pedro de Alcantara, Caceres, Spain

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

June 1, 2011

Primary Completion (Actual)

October 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

September 2, 2011

First Submitted That Met QC Criteria

September 2, 2011

First Posted (Estimate)

September 5, 2011

Study Record Updates

Last Update Posted (Estimate)

May 25, 2016

Last Update Submitted That Met QC Criteria

April 16, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MIDP11

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

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.

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