Dexamethasone, Can it Replace Ketoprofen in the Strategy of Intraoperative Multimodal Analgesia in Paediatric Surgery ? A Prospective Randomized Double-blinded Study. DEXA OP (DEXA OP)

Postoperative pain and nausea-vomiting (PONV) are the first causes of failure in ambulatory care in pediatric surgery. Actually, the paracetamol/ketoprofen combination in intraoperative care is recommended for effective postoperative analgesia in children. However, intravenous ketoprofen doesn't have the marketing authorization for use in children less than 15 years old and its use is mainly justified by the absence of therapeutic alternatives. Recently, findings from published studies suggest that dexamethasone (DXM), which is actually recommended to prevent PONV for children "at risk", at a dose of 0.1mg/kg, would have analgesic properties above 0.15 mg/kg comparable to non-steroidal anti-inflammatories (NSAI).

Main objective :

To examine the effects of intraoperative DXM (0.2mg/kg and 0.4mg/kg) on the intensity of postoperative pain in the post-anaesthetic care unit (PACU) compared to ketoprofen (1mg/kg).

Secondary objectives :

To examine the effects of intraoperative DXM (0.2mg/kg and 0.4mg/kg) compared to ketoprofen (1mg/kg) on the anesthesia emergence delirium, the intensity of postoperative pain, the consumption of rescue analgesics and the side effects in the first 24 hours after surgery.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: Dexamethasone 0.2 mg/kg; Drug: Dexamethasone 0.4 mg/kg; Drug: Ketoprofen 1 mg/kg

Detailed Description

Methodology :

Non inferiority, phase III, therapeutic trial. Prospective, randomized double-blinded, monocentric study. Inclusion of 567 patients. Inclusion will be performed by the anesthesiologist, the day of surgery during the preoperative visit.

Each patient will be randomised to receive intraoperative DXM (0.2mg/kg), DXM (0.4mg/kg) (max 20mg) or ketoprofen (1mg/kg) (max 100mg).

The clinical data will be collected prospectively in an electronic database. If the hypothesis of non-inferiority is verified, it is planned to test the superiority of the hypothesis secondarily.

Treatment :

Single injection of DXM (Mylan Dexamethasone® 20 mg/5 ml or 4 mg/1 ml injection ampoule solution) at 0.2 mg / kg or 0.4 mg/kg or single injection of ketoprofen (Medac ketoprofen ® 100 mg/4 ml injection ampoule solution) at 1 mg /kg after general anesthesia induction and before surgery incision.

• Study Type: Interventional
• Enrollment (Actual): 580
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Brittany
    • Rennes, Brittany, France, 35000
      • Rennes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children, aged 1 to 16 years
• Undergoing surgery (orchiopexy, inguinal hernia, circumcision, adenoidectomy, tonsillectomy or orthopedic act with osteosynthesis)
• Parental consent

Exclusion Criteria:

• Contraindication to NSAI or DXM
• Hypersensitivity to ketoprofen, DXM, hypnovel or atarax
• Porphyria
• Long QT Syndrome
• Renal or hepatic impairment
• Corticosteroid consumption the week before surgery
• NSAI consumption within 48 hours before surgery
• IV induction for full stomach or myopathic patient.
• French language not spoken by parents.
• Simultaneous participation in biomedical research on health products

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexamethasone 0.2 mg/kg; Single injection of DXM (Mylan Dexamethasone® 20 mg/5 ml or 4 mg/1 ml injection ampoule solution) at 0.2 mg / kg after general anesthesia induction and before surgery incision.	Drug: Dexamethasone 0.2 mg/kg; Single injection of DXM (Mylan Dexamethasone® 20 mg/5 ml or 4 mg/1 ml injection ampoule solution) at 0.2 mg / kg after general anesthesia induction and before surgery incision.
Experimental: Dexamethasone 0.4 mg/kg; Single injection of DXM (Mylan Dexamethasone® 20 mg/5 ml or 4 mg/1 ml injection ampoule solution) at 0.4 mg / kg after general anesthesia induction and before surgery incision.	Drug: Dexamethasone 0.4 mg/kg; Single injection of DXM (Mylan Dexamethasone® 20 mg/5 ml or 4 mg/1 ml injection ampoule solution) at 0.4 mg / kg after general anesthesia induction and before surgery incision.
Active Comparator: Ketoprofen 1 mg/kg; Single injection of ketoprofen (Medac ketoprofen ® 100 mg/4 ml injection ampoule solution) at 1 mg /kg after general anesthesia induction and before surgery incision.	Drug: Ketoprofen 1 mg/kg; Single injection of ketoprofen (Medac ketoprofen ® 100 mg/4 ml injection ampoule solution) at 1 mg /kg after general anesthesia induction and before surgery incision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum intensity of postoperative pain	Maximum intensity of postoperative pain assessed in PACU using the Faces Legs Activity Cry Consolability tool (FLACC, 0-10)	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pediatric Anesthesia Emergence Delirium Scale (PAEDS)	Pediatric Anesthesia Emergence Delirium Scale (PAEDS)	24 hours
Intensity of postoperative pain	Intensity of postoperative pain assessed in ambulatory unit and at home one day after surgery. (FLACC, 0-10).	24 hours
Rescue analgesic consumption	Rescue analgesic consumption in the PACU, ambulatory unit and at home.	24 hours
Side effects	Side effects during hospitalization (PONV, postoperative bleeding) and in the first 24 hours post-surgery (PONV, fever, bleeding, behavior modification and sleep disorders).	24 hours
Length of stay	Length of stay in ambulatory unit (time of possible discharge using Pediatric Post Anesthetic Discharge Scoring System and the actual time of discharge).	24 hours
Parent's satisfaction	Parent's satisfaction on a four-point Likert scale	24 hours

Collaborators and Investigators

• Sponsor: Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2015
• Primary Completion (Actual): July 18, 2019
• Study Completion (Actual): July 18, 2019

Study Registration Dates

• First Submitted: March 23, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimate): March 26, 2015

Study Record Updates

• Last Update Posted (Actual): November 6, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Paediatric surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Ketoprofen
• Other Study ID Numbers: 35RC14_9853_DEXA OP; 2014-005026-35 (EudraCT Number); 141557A-32 (Other Identifier: ANSM)