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: December 15, 2011
Last verified: December 2011
  Purpose

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 Intervention Phase
Drug Safety
Drug: Midazolam
Drug: Propofol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
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

Resource links provided by NLM:


Further study details as provided by Infante, Javier Molina, M.D.:

Primary Outcome Measures:
  • Level of sedation throughout the entire procedure [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 135
Study Start Date: June 2011
Study Completion Date: December 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Midazolam balanced propofol 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
Placebo Comparator: Single-agent propofol sedation 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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01428882

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

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Javier Molina-Infante, MD, Medical Doctor, Infante, Javier Molina, M.D.
ClinicalTrials.gov Identifier: NCT01428882     History of Changes
Other Study ID Numbers: MIDP11
Study First Received: September 2, 2011
Last Updated: December 15, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Infante, Javier Molina, M.D.:
Propofol
Midazolam
Moderate sedation
Deep sedation
Colonoscopy

Additional relevant MeSH terms:
Midazolam
Propofol
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014