Effect of A Single Dose of Lorazepam on Salivary Cortisol Response in Children Undergoing Digestive Endoscopy: (Endo-Lora)

Effect of A Single Dose of Lorazepam on Salivary Cortisol Response in Children Undergoing Digestive Endoscopy: a Randomized Double Blinded Study

The purpose of this study is to determine the effect of a single dose of Lorazepam on salivary cortisol in children undergoing digestive endoscopy. To do so, the patients will be randomized in three groups. The first group receives the Lorazepam, the second group receives a placebo and the last group receives no intervention. Each patient will have three saliva samples taken at three different time point on the day of the endoscopy and will be asked to fill out questionnaires on anxiety and overall satisfaction of the procedure.

Study Overview

• Status: Completed
• Conditions: Anxiety
• Intervention / Treatment: Drug: Lorazepam; Other: Placebo

Detailed Description

Background: Pediatric digestive endoscopies (gastroscopy and colonoscopy) are invasive procedures. All endoscopic procedure are conducted in the operating room either under intravenous (IV) sedation or general anesthesia. More than 50% of procedures are performed using IV sedation. The current sedation protocol in the endoscopy suite is a combination of Midazolam (0.1 mg/kg) and Fentanyl (1 microgram/kg) in all children. The children undergoing colonoscopies receive and additional administration of Ketamine (0.5 mg/kg).

In a previous study performed in children 10-18 years undergoing upper and lower endoscopy, the investigators found that despite this regimen, 25% of the children expressed a significantly high level of pain during endoscopy under IV sedation.

Because general anesthesia is not available for all children, it is important to investigate strategies that could help in minimizing the discomfort and pain during the procedure.

Salivary cortisol (sCortisol) has been used in several pediatric studies to determine the level of stress in children prior to various medical procedures. In another study done at our site, the investigators have found sCortisol to be a reliable biomarker of stress for children undergoing digestive endoscopies. Furthermore, the mean baseline sCortisol levels were higher in the group that experienced procedural pain.

Lorazepam is a a rapid onset benzodiazepine that has anxiolytic and sedative properties that has been approved by Health Canada as an adjunct therapy for the relief of excessive anxiety that might be present prior to surgical interventions.

Objective:

The primary objective is to investigate the effect of Lorazepam as compared to placebo on the change of the level of sCortisol between baseline (C1) and immediately before endoscopy (C2) in adolescents undergoing a gastroscopy or a colonoscopy. The investigators think that it might be possible to modulate the stress response with the administration of a benzodiazepine as soon as the children arrives at the hospital. Thus children could have a better experience of the digestive endoscopic procedure (less pain and more comfort).

The secondary outcome measure will be:

(1) the proportion of children experiencing procedural pain, (2) the duration of endoscopic procedures, (3) children satisfaction, (4) physician and nurse satisfaction (5) the total dose of Fentanyl and Ketamine per kilogram body weight delivered during the procedure and (6) the mean change between pre-op and postop cortisol levels between the two groups.

Safety outcomes measures: The following adverse events will be sought before and during the endoscopy: prolonged drowsiness, hypotension, hypertension, desaturation, bradycardia.

Exploratory outcomes: the mean change between pre-op and postop cortisol levels in the Group C (No intervention) compared to Group A and B.

Methods:

In this randomized controlled trial children will be assigned to one of the three following groups (no intervention, placebo and active drug). The investigators will collect salivary samples to measure the levels of sCortisol and investigate their variation between three timepoint ( at arrival at the hospital, right before the procedure and right after the procedure). sCortisol levels will be correlated to a questionnaire evaluating the anxiety level in the patient. The research team will also evaluate the pain experienced during the procedure using the Nurse-Assessed Patient Comfort Score (NAPCOMS): a validated tool for the evaluation of pain in subjects undergoing endoscopies).

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children aged 9-18 seen in our endoscopic unit
• Children undergoing upper, lower or combined digestive endoscopy
• Procedure to be performed within 3 hours of inclusion in the study and drug administration

Exclusion Criteria:

• Unable to read or speak English or French
• Diagnosed with a psychiatric or neurological disorder
• Myasthenia gravis
• Acute narrow angle glaucoma
• Known hypersensitivity to benzodiazepines
• Already treated with an anxiolytic on a regular basis
• Receiving a drug contraindicated in association with benzodiazepines
• Receiving oral, intravenous or inhaled corticosteroids in the last two days before randomization
• Body weight less than 20 kg
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; Patient will receive a single dose of either 0,5mg or 1mg of oral Lorazepam depending on their body weight.	Drug: Lorazepam; Patient receives one or two tablet of 0,5mg Lorazepam according to body weight; Other Names: Apo-Lorazepam
Placebo Comparator: Group B; Patient will receive a placebo similar in color, form and size.	Other: Placebo; Patient receive one of two tablet of Placebo according to body weight
No Intervention: Group 3; Patient will receive no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of sCortisol from baseline to one hour after drug administration	Proportion of children with a decrease of sCortisol of at least 15 points between the group Placebo and the group Lorazepam	One hour after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural pain	Proportion of children experiencing procedural pain	during endoscopic procedure
Duration of endoscopic procedure	Duration of endoscopic procedure. The time interval in minutes will be measured between the start and the end of each procedure.	Through completion of endoscopy: an average of 2 hours after drug administration
Children Satisfaction	Children satisfaction will be evaluated with a validated Satisfaction questionnaire of children undergoing endoscopy	Through study completion, an average of 3 hours
Physician Satisfaction	Physician satisfaction will be evaluated with a validated tool : CLINICIAN SATISFACTION WITH SEDATION INSTRUMENT (CSSI)	during the endoscopic procedure
Nurse Satisfaction	Nurse satisfaction will be evaluated with a validated tool : NURSE ASSESSED PATIENT COMFORT SCORE (NAPCOMS)	during the endoscopic procedure
Medication needed For sedation	Total dose of Fentanyl and Ketamine per kilogram body weight delivered	during the procedure
Change in sCortisol levels between pre-op and post-op	Mean change between pre-op and post-op cortisol levels between the two groups (Lorazepam and Placebo)	one hour after the endoscopic procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment-related Adverse Events (Safety and Tolerability)	The following adverse events will be sought before and during the endoscopy: prolonged drowsiness, hypotension, hypertension, desaturation, bradycardia.	during the procedure
Change in level of sCortisol between pre-op and post-op in the group without any intervention	the mean change between pre-op and post-op cortisol levels in the Group C (No intervention)	Through study completion, an average of 3 hours

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Investigators: Principal Investigator: Prévost Jantchou, MD, PhD, Ste-Justine Hospital

Publications and helpful links

General Publications

• Chennou F, Bonneau-Fortin A, Portolese O, Belmesk L, Jean-Pierre M, Cote G, Dirks MH, Jantchou P. Oral Lorazepam is not Superior to Placebo for Lowering Stress in Children Before Digestive Endoscopy: A Double-Blind, Randomized, Controlled Trial. Paediatr Drugs. 2019 Oct;21(5):379-387. doi: 10.1007/s40272-019-00351-9.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2017
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: June 2, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: September 4, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Lorazepam
• Other Study ID Numbers: JP2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No