- Solid Tumors
- Pipeline Molecules
- Alliance Partners
Our mission is to provide healthcare professionals with unbiased clinical research information, easily.
Currently, you can access the following clinical trials being conducted worldwide:
Clinicaltrials.gov identifier NCT03931057
Recruitment Status Recruiting
First Posted April 29, 2019
Last update posted September 9, 2020
To evaluate the effect of ADV6209, a new oral Midazolam formulation, on preoperative anxiety and sedation levels in paediatric anaesthesia Primary Objective: Sedation score (mYPAS) 30 min after administration of the premedication drug Secondary Objective: Acceptance of anaesthesia mask induction Acceptance of oral administration of the premedication drug
Premedication represents an important part in the perioperative management of children and is used to reduce pre-operative stress as well as to facilitate induction of inhaled anaesthesia. Midazolam is the drug most often used for premedication in infants and children because it provides good sedation, anxiolytic and amnestic effects and few side effects. Oral intake of the drug is the most preferred route of administration by paediatric patients, whereas the majority of existing oral Midazolam solutions involve the use of i.v. Midazolam formulation given orally, unregistered or off-label. Moreover i.v. Midazolam solutions are often not well accepted by children because of their bitter taste. Considering the lack of available oral medications for moderate sedation in children in most European countries, ADV6209, an innovative 0.2% (w/v) oral solution of Midazolam for children from six months of age, was developed. The formation of a γ-Cyclodextrin -Midazolam complex, representing a new chemical formula, was used to improve the solubility and the palatability of the Midazolam formulation. A pharmacokinetic (PK) study has been executed in adults, children and adolescents, whereas ADV6209 showed improvements to current extemporaneous oral solutions of midazolam (EOM) preparations in terms of taste and easiness of use while presenting a similar PK profile. Satisfying sedation, measured with the Observer Assessment of Alertness/Sedation Scale (OAA score / S≤17) was observed in 78.4% of paediatric patients 30 minutes after ADV6209 administration. Anxiety score (modified Yale Preoperative Anxiety Scale - mYPAS) was decreased by 18.3% on average over baseline, 30 minutes after ADV6209 with a more pronounced effect in the youngest children who were also the most anxious prior to administration of the drug. In general the treatment was well accepted by all children and did not induce more crying and nausea / vomiting than before Midazolam. ADV6209 seems a very promising premedication drug. It has been licensed by the EU regulatory authorities to become the first licensed paediatric sedative in the EU (September 2018). It may help to avoid unregistered and off label use of EOM. Consequently, we want to evaluate the efficacy and safety of ADV6209 on preoperative anxiety and sedation levels in paediatric anaesthesia in daily clinical routine in this randomized, controlled, double blinded study.
ADV6209 (= gamma-cyclodextrin-Midazolam) 0.3 mg/kg p.o. once 30 min. before anesthesia
Drug: ADV6209 (=gamma-cyclodextrin-Midazolam)
30 min. before anesthesia children have to swallow the anxiolytic drug (ADV6209)
|Active Comparator: Midazolam
Midazolam (in orange flavored syrup) 0.3 mg/kg p.o. once 30 min. before anesthesia
30 min. before anesthesia children have to swallow the anxiolytic drug Midazolam
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, , Learn About Clinical Studies.-->
- ASA 1 and 2 children from 2-8 years scheduled for elective surgical or diagnostic
procedures, where premedication would be used in clinical routine
- Signed written parental informed consent prior to inclusion in the study
- ASA 3-5
- Allergy against the study drug
- Participation in another clinical study investigating another IMP within one month
prior to screening
- Other objections to study participation in the opinion of the investigator
- Parent's or legal guardian's refusal of participation of the child
Contact: Peter Marhofer, MD 0043140400 ext 19227 email@example.com
Contact: Markus Zadrazil, MD 0043140400 ext 19227 firstname.lastname@example.org
Medical University of Vienna, Dept. of Anesthesia, Intensive Care Medicine and Pain Medicine
Medical University of Vienna
Principal Investigator: Peter Marhofer, MD Medical University of Vienna
Kain ZN, Caldwell-Andrews AA, Krivutza DM, Weinberg ME, Wang SM, Gaal D. Trends in the practice of parental presence during induction of anesthesia and the use of preoperative sedative premedication in the United States, 1995-2002: results of a follow-up national survey. Anesth Analg. 2004 May;98(5):1252-9, table of contents.
Marçon F, Mathiron D, Pilard S, Lemaire-Hurtel AS, Dubaele JM, Djedaini-Pilard F. Development and formulation of a 0.2% oral solution of midazolam containing gamma-cyclodextrin. Int J Pharm. 2009 Sep 11;379(2):244-50. doi: 10.1016/j.ijpharm.2009.05.029. Epub 2009 May 23.
Cuzzocrea F, Gugliandolo MC, Larcan R, Romeo C, Turiaco N, Dominici T. A psychological preoperative program: effects on anxiety and cooperative behaviors. Paediatr Anaesth. 2013 Feb;23(2):139-43. doi: 10.1111/pan.12100.
Davidson AJ, Shrivastava PP, Jamsen K, Huang GH, Czarnecki C, Gibson MA, Stewart SA, Stargatt R. Risk factors for anxiety at induction of anesthesia in children: a prospective cohort study. Paediatr Anaesth. 2006 Sep;16(9):919-27.
Fortier MA, MacLaren JE, Martin SR, Perret-Karimi D, Kain ZN. Pediatric pain after ambulatory surgery: where's the medication? Pediatrics. 2009 Oct;124(4):e588-95. doi: 10.1542/peds.2008-3529. Epub 2009 Sep 7.
Marçon F, Guittet C, Manso MA, Burton I, Granier LA, Jacqmin P, Dupont H. Population pharmacokinetic evaluation of ADV6209, an innovative oral solution of midazolam containing cyclodextrin. Eur J Pharm Sci. 2018 Mar 1;114:46-54. doi: 10.1016/j.ejps.2017.11.030. Epub 2017 Dec 5.
Huet A, Lucas-Polomeni MM, Robert JC, Sixou JL, Wodey E. Hypnosis and dental anesthesia in children: a prospective controlled study. Int J Clin Exp Hypn. 2011 Oct-Dec;59(4):424-40. doi: 10.1080/00207144.2011.594740.