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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Javier Molina-Infante, MD, Infante, Javier Molina, M.D.
ClinicalTrials.gov Identifier:
NCT01428882
First received: September 2, 2011
Last updated: April 16, 2016
Last verified: April 2016

September 2, 2011
April 16, 2016
June 2011
October 2011   (final data collection date for primary outcome measure)
Level of Sedation Throughout the Entire Procedure [ Time Frame: Up to 1 hour after introduction of the colonoscope ] [ Designated as safety issue: No ]
Assessment every two minutes of the level of sedation during the endoscopic procedure, rating it as minimal, moderate or deep.
Level of Sedation Throughout the Entire Procedure [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01428882 on ClinicalTrials.gov Archive Site
  • Duration of Recovery After the Endoscopic Procedure [ Time Frame: Up to 1 hour after colonoscopy ] [ Designated as safety issue: No ]

    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

  • Rate of Sedation-related Complications During the Procedure and the Recovery Phases [ Time Frame: Up to two hours, including colonoscopy performance and recovery period ] [ Designated as safety issue: Yes ]
    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.
  • 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 ] [ Designated as safety issue: No ]

    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".

  • Duration of Recovery After the Endoscopic Procedure [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Rate of Sedation-related Complications During the Procedure and the Recovery Phases [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Rate of Patients and Physician Satisfaction With Sedation [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Propofol vs. Midazolam-based Balanced Propofol for Nonanesthesiologist Moderate Sedation in Colonoscopy
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.

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

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Procedural Sedation
  • 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
  • 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
  • Active Comparator: Midazolam balanced propofol sedation
    2 mg midazolam in 2 ml saline midazolam followed by continuous propofol iv infusion
    Intervention: Drug: Midazolam
  • Placebo Comparator: Single-agent propofol sedation
    2 ml saline followed by continuous propofol iv infusion
    Intervention: Drug: Propofol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
135
December 2011
October 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01428882
MIDP11
Yes
Yes
Not Provided
Javier Molina-Infante, MD, Infante, Javier Molina, M.D.
Infante, Javier Molina, M.D.
Not Provided
Principal Investigator: Javier Molina-Infante, MD Hospital San Pedro de Alcantara, Caceres, Spain
Infante, Javier Molina, M.D.
April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP