Prospective, Randomized, Double-blind, Double-dummy, Active-controlled, Phase 3 Clinical Trial Comparing the Safety and Efficacy of Intranasal Dexmedetomidine to Oral Midazolam as Premedication for Propofol Sedation in Pediatric Patients Undergoing Magnetic Resonance Imaging
试验速览
- 阶段
- 3 期
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Incidence of bradycardia
研究概览
简要总结
A magnetic resonance imaging (MRI) examination usually takes 30 to 45 minutes and requires the patient to remain perfectly still during the entire acquisition process to ensure quality. Children under 6 years of age are not very cooperative and sedation is required for this age group.
Currently, there are no specific recommendations for sedation for a paediatric MRI examination. In 2018, a retrospective study on the sedation protocol applied at Hôpital Universitaire des Enfants Reine Fabiola (H.U.D.E.R.F.) was conducted. In this protocol, premedication was done with oral midazolam and sedation with iterative boluses of propofol. This study concluded that the protocol in place was effective, but found that image acquisition during the procedure was interrupted in 25% of cases, largely due to involuntary movements of the child.
Preoperative stress can be emotionally traumatic for the child and may even extend beyond the perioperative period, hence the importance of premedication. For the most anxious children, non-pharmacological means of premedication are often not sufficient. Moreover, the literature shows that pharmacological premedication is useful in reducing parental separation anxiety and in facilitating induction of anaesthesia.
Midazolam is an effective premedication agent with some disadvantages (paradoxical reaction, low compliance of oral intake). Dexmedetomidine is a highly effective α-2 receptor agonist that can also be used as premedication according to the current literature. A report by the Pediatric Sedation Research Consortium (P.S.R.C.) shows that it has a safe profile and an incidence rate of serious adverse events of 0.36% in the paediatric population. Furthermore, administered intranasally, it is non-invasive, painless and has good bioavailability (over 80%).
The primary objective is to demonstrate the superiority of intranasal dexmedetomidine over oral midazolam as a premedication for bolus sedation of propofol in terms of the incidence of any event during the MRI procedure requiring temporary or permanent interruption of the examination.
The impact of dexmedetomidine on the amount of propofol administered and on the post-sedation period, the impact of external factors on the primary objective, the acceptance of intranasal premedication by the children and the quality of the MRI images will also be analyzed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Patients will be assessed in the preoperative anaesthesia consultation. If they meet the criteria for inclusion in our protocol, and have no exclusion criteria, the study will be explained to their parents (and to the child in simple language if they are old enough to understand). On the sedation day, randomisation is carried out by the clinical research unit of the H.U.D.E.R.F. The result of the randomisation is transmitted in opaque and sealed envelopes to the non-blinded members of the team who are responsible for preparing the premedications. Once prepared and anonymously labelled, the premedication is administered to the patient by the blinded nursing staff. The child is monitored for the next 30 minutes. Ten minutes before the examination, the child and his/her parents are taken to the induction room to meet the anesthesiologist who will take charge of the child.
入排标准
- 年龄范围
- 6 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children of both sexes, aged 6 months to 6 years,
- •ASA score I to IV,
- •Requiring standard magnetic resonance imaging due to clinical condition, regardless of underlying pathology,
- •Sedation performed by an anesthesiologist,
- •Written informed consent in accordance with the ICH-GCP and local legislation prior to trial entry.
排除标准
- •Contraindications to MRI (cardiac pacemaker, neurostimulator, ferromagnetic implant),
- •Sedation carried out by a non-anesthesiologist,
- •Emergency MRI,
- •Presence of head trauma,
- •Presence of nasal congestion or upper respiratory tract infection on the day of sedation,
- •Multiple procedures during the same sedation (operating room, evoked potentials, etc.),
- •Children with pathologies requiring airway safety,
- •Any known allergic or hypersensitivity reaction to dexmedetomidine,
- •Any known allergic or hypersensitivity reaction to benzodiazepines,
- •Concomitant use of negative chronotropes, as Digoxine,
- •Patient known with chronic respiratory failure or myasthenia,
- •Patient known with anatomical abnormality of the airway, lung disease or sleep apnea syndrome
- •Patient with known cardiac rhythm abnormality or cardio-vascular disease,
- •Patient with known hepatic disorder or chronic kidney disease,
- •Patient with hypotension or bradycardia on the day of the examination,
- •Patient with a BMI > 97th percentile (which corresponds to overweight, including obesity).
研究组 & 干预措施
Group Midazolam
Administration of oral midazolam (0.25 mg/kg) as premedication before propofol-based sedation.
The patient receives an oral premedication containing 0.125mL/kg of midazolam (which corresponds to a dosage of 0.25mg/kg of Ozalin® 2mg/ml, with a maximum of 20 mg). He/she also receives an intranasal spray containing matching placebo of dexmedetomidine (NaCl 0.9%). The volume administered corresponds to 0.02 mL/kg (which corresponds to a dosage of 2 mcg/kg of pure dexmedetomidine 100 mcg/mL in group D).
干预措施: Midazolam (Drug)
Group Dexmedetomidine
Administration of intranasal dexmedetomidine as premedication before propofol-based sedation.
The patient receives an intranasal premedication containing 2 mcg/kg of dexmedetomidine. He/she also receives an oral solution containing matching placebo of midazolam (flavored-water prepared by the pharmacy). The volume administered corresponds to 0.125 mL/kg (which corresponds to a dosage of 0.25mg/kg of Ozalin® 2mg/mL, with a maximum of 20 mg or 10mL).
干预措施: Dexmedetomidine (Drug)
结局指标
主要结局
Incidence of bradycardia
时间窗: 6 hours
Incidence of bradycardia (defined as a decrease of 2 standard deviations from normal for age, as described by the American Heart Association (AHA) in the Pediatric Advanced Life Support (PALS) manual, and which requires intervention by the anesthesiologist in charge of the patient to improve heart rate and cardiac output); expressed as percentage of patients
Movements
时间窗: 6 hours
Incidence of involuntary movements requiring intervention by the anesthesiologist in charge of the patient to deepen sedation; expressed as percentage of patients
Hypotension
时间窗: 6 hours
Incidence of hypotension (defined as a systolic blood pressure below the 5th percentile for age, as described by the AHA in the PALS manual, and which requires intervention by the anesthesiologist in charge of the patient to improve blood pressure); expressed as percentage of patients
Desaturation
时间窗: 6 hours
Incidence of oxygen desaturation under 95% (defined as moderate if SpO2 is between 90 and 95%, severe if below 90%); expressed as percentage of patients
次要结局
未报告次要终点
研究者
Denis SCHMARTZ
Head, department of Anesthesiology
Brugmann University Hospital