Effect of A Single Dose of Lorazepam on Salivary Cortisol Response in Children Undergoing Digestive Endoscopy:

NCT ID: NCT03180632

Last Updated: 2018-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-28
• Study Completion Date: 2018-06-01

Brief Summary

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.

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).

Conditions

Anxiety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A

Patient will receive a single dose of either 0,5mg or 1mg of oral Lorazepam depending on their body weight.

Group Type: ACTIVE_COMPARATOR

Lorazepam

Intervention Type: DRUG

Patient receives one or two tablet of 0,5mg Lorazepam according to body weight

Group B

Patient will receive a placebo similar in color, form and size.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Patient receive one of two tablet of Placebo according to body weight

Group 3

Patient will receive no intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Lorazepam

Patient receives one or two tablet of 0,5mg Lorazepam according to body weight

Intervention Type: DRUG

Placebo

Patient receive one of two tablet of Placebo according to body weight

Intervention Type: OTHER

Other Intervention Names

Apo-Lorazepam

Eligibility Criteria

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

• Minimum Eligible Age: 9 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Justine's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jantchou Prevost

MD,PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prévost Jantchou, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ste-Justine Hospital

Locations

CHU Sainte-Justine

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 31418168 (View on PubMed)

Other Identifiers

JP2017

Identifier Type: -

Identifier Source: org_study_id