Trial Outcomes & Findings for A Single-centre Study of Entonox Versus Midazolam Sedation in Gastroscopy (NCT NCT01744184)

NCT ID: NCT01744184

Last Updated: 2024-11-12

Results Overview

Percentage of patients with a score of 4 or 5 on the 5-point modified global rating scale comfort score, as measured by the patient, will be compared between the midazolam and entonox groups, per protocol. The comfort score ranges from 1-5 with 1 meaning patient was in extreme discomfort frequently during procedure and 5 being no discomfort, resting comfortably throughout. The score is completed by the patient while they are in the recovery area post procedure and prior to discharge from the unit.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 62 participants
• Primary outcome timeframe: During gastroscopy procedure
• Results posted on: 2024-11-12

Participant Flow

Participant milestones

Measure	Midazolam midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Overall Study STARTED	32	30
Overall Study COMPLETED	31	29
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Midazolam midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Age was not collected. All participants were 18 or over to be eligible for the study.

Baseline characteristics by cohort

Measure	Midazolam n=32 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm	Total n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.
Age, Categorical Between 18 and 65 years	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.
Age, Categorical >=65 years	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.	0 Participants Age was not collected. All participants were 18 or over to be eligible for the study.
Sex: Female, Male Female	0 Participants Gender data was not collected.	0 Participants Gender data was not collected.	0 Participants Gender data was not collected.
Sex: Female, Male Male	0 Participants Gender data was not collected.	0 Participants Gender data was not collected.	0 Participants Gender data was not collected.
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United Kingdom	32 participants n=32 Participants	30 participants n=30 Participants	62 participants n=62 Participants

PRIMARY outcome

Timeframe: During gastroscopy procedure

Percentage of patients with a score of 4 or 5 on the 5-point modified global rating scale comfort score, as measured by the patient, will be compared between the midazolam and entonox groups, per protocol. The comfort score ranges from 1-5 with 1 meaning patient was in extreme discomfort frequently during procedure and 5 being no discomfort, resting comfortably throughout. The score is completed by the patient while they are in the recovery area post procedure and prior to discharge from the unit.

Outcome measures

Measure	Midazolam n=32 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Percentage of Patients Mild or no Discomfort During Gastroscopy	87.5 percentage of participants	63.3 percentage of participants

SECONDARY outcome

Timeframe: Day of procedure

The percentage of participants with completed procedures in both arms of the study confirmed by data collection.

Outcome measures

Measure	Midazolam n=32 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Number of Participants With Completed Procedures in Both Arms of the Study.	100 Percentage of participants	96.7 Percentage of participants

SECONDARY outcome

Timeframe: Defined as start time to end time of gastroscopy.

Comparison of procedure time, defined as start time to end time in the per protocol population, between the two groups.

Outcome measures

Measure	Midazolam n=32 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Comparison of Procedure Time	4 Minutes Interval 3.0 to 14.0	5 Minutes Interval 2.0 to 19.0

SECONDARY outcome

Timeframe: Procedure to discharge

Comparison of gastroscopy procedure start time to discharge from endoscopy department post-procedure care time in the per protocol population between the two groups.

Outcome measures

Measure	Midazolam n=32 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Comparison of Procedure Start Time to Discharge.	86 Minutes Interval 20.0 to 217.0	46 Minutes Interval 16.0 to 143.0

SECONDARY outcome

Timeframe: Consent to 72 hours post discharge from the endoscopy unit which is the same day as the procedure.

Number of patients reporting adverse events.

Outcome measures

Measure	Midazolam n=32 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Number of Patients With Adverse Events.	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Completed after procedure completion during the post-procedure care and prior to discharge from the endoscopy unit.

Population: 1 participant in the Midazolam cohort did not complete the Visual Analogue Scale post procedure prior to discharge.

Comparison of VAS (Visual Analogue Scale) scores between the two groups (per protocol). The scale ranges between 0 and 100 where 0 is the worst imaginable experience and 100 being very comfortable. The visual measure is a 100mm line and the score is measured by the participant marking on the line how they felt the procedure was. The research team then measure the line and confirm the score to the nearest mm to get a score of 0-100.

Outcome measures

Measure	Midazolam n=31 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Comparison of Visual Analogue Scale Scores.	90 score on a scale Interval 20.0 to 100.0	80 score on a scale Interval 20.0 to 100.0

SECONDARY outcome

Timeframe: Completed after procedure completion during the post-procedure care and prior to discharge from the endoscopy unit.

Percentage of patients with a score of 4 or 5 on the 5-point comfort scale, as measured by the endoscopy nurse, will be compared between the midazolam and Entonox groups, per protocol. The comfort score ranges from 1-5 with 1 meaning patient was in extreme discomfort frequently during procedure and 5 being no discomfort, resting comfortably throughout. This score is completed by the endoscopy nurse immediately following the patients procedure.

Outcome measures

Measure	Midazolam n=32 Participants midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 Participants Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
5-point Modified Global Rating Scale Comfort Nurse Score	31 Participants	28 Participants

Adverse Events

Midazolam

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Entonox

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Midazolam n=32 participants at risk midazolam sedation combined with pharyngeal anaesthesia Participants randomized to receive midazolam will have an intravenous cannula sited and, following the administration of xylocaine throat spray as above, will be put into the left lateral position. They will then be given up to 5mg midazolam as appropriate to achieve conscious sedation as for standard protocol in endoscopy. Midazolam: up to 5mg midazolam as appropriate	Entonox n=30 participants at risk Entonox combined with pharyngeal anaesthesia. Pharyngeal anaesthesia, given as 8-16 sprays of xylocaine to the pharynx; 3 minutes will be given to allow the pharynx to become anaesthetized. Participants randomized to receive Entonox will be given the 50:50 nitrous oxide:oxygen mix via a mouthpiece with a demand valve system, once in position for the procedure. Inhalations will be given for 3-5 minutes (or until the participant feels adequately sedated) measured using a stopwatch. Oxygen will be given at 2 litres per minute via nasal cannulae during the procedure, (standard care for sedated procedures). The endoscopist will then proceed to intubate the cricopharynx and perform the procedure in the standard manner. Entonox: Entonox arm
Skin and subcutaneous tissue disorders Allergic Reaction	3.1% 1/32 • Number of events 1 • From participant consent until 72 hours post procedure. Adverse events were monitored while the patient was on site following consent until they were discharged from the endoscopy unit. A follow up phone call was completed 72 hours after the participant was discharged and the participants were asked to recall any adverse events that have occurred since their discharge.	0.00% 0/30 • From participant consent until 72 hours post procedure. Adverse events were monitored while the patient was on site following consent until they were discharged from the endoscopy unit. A follow up phone call was completed 72 hours after the participant was discharged and the participants were asked to recall any adverse events that have occurred since their discharge.
Eye disorders Blurred Vision	0.00% 0/32 • From participant consent until 72 hours post procedure. Adverse events were monitored while the patient was on site following consent until they were discharged from the endoscopy unit. A follow up phone call was completed 72 hours after the participant was discharged and the participants were asked to recall any adverse events that have occurred since their discharge.	3.3% 1/30 • Number of events 1 • From participant consent until 72 hours post procedure. Adverse events were monitored while the patient was on site following consent until they were discharged from the endoscopy unit. A follow up phone call was completed 72 hours after the participant was discharged and the participants were asked to recall any adverse events that have occurred since their discharge.
Nervous system disorders Shivering	0.00% 0/32 • From participant consent until 72 hours post procedure. Adverse events were monitored while the patient was on site following consent until they were discharged from the endoscopy unit. A follow up phone call was completed 72 hours after the participant was discharged and the participants were asked to recall any adverse events that have occurred since their discharge.	3.3% 1/30 • Number of events 1 • From participant consent until 72 hours post procedure. Adverse events were monitored while the patient was on site following consent until they were discharged from the endoscopy unit. A follow up phone call was completed 72 hours after the participant was discharged and the participants were asked to recall any adverse events that have occurred since their discharge.

Additional Information

Dr Simon McLaughlin

University Hospitals Dorset NHS Foundation Trust

Phone: 01202303626

Email: Simon.McLaughlin@uhd.nhs.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place