E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Midazolam is a drug with sedative properties. In children, it is used to reduce stress, anxiety and discomfort associated with clinical procedures for example surgery. It is also used to reduce stress and discomfort in critically ill children attached to mechanical ventilators in intensive care.
Our long term aim is to develop personalised dosing schedules for children receiving midazolam intravenously.
The principal objective of this study is to determine whether criticallyill
children metabolise midazolam differently to otherwise healthy children undergoing routine surgery. |
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E.2.2 | Secondary objectives of the trial |
The study has two secondary objectives.
The first is to determine how well a computer program called ‘Simcyp Paediatric Simulator’ predicts midazolam metabolism in critically ill
children and in otherwise healthy children undergoing surgery.
The second is to determine whether blood midazolam level measurements made from microvolume samples of
dried blood are equivalent to blood midazolam measurements made using wet blood samples. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Children aged between 1 month (corrected gestational age) and less than 16 years admitted to University Hospitals of Leicester either to Paediatric Intensive Care or for planned surgical procedures requiring general anaesthesia.
• Children commenced on intravenous (IV) midazolam therapy by the direct care team.
• Parents or legal guardians of children willing to provide written consent for their child to take part in the study.
• Where appropriate, children provide written assent to take part in the study. |
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E.4 | Principal exclusion criteria |
• Children who refuse assent and children whose parents or legal guardian refuse consent will be excluded from the study.
• Any significant disease or disorder which, in the opinion of the direct care team, may either put the participant at risk because of study participation or adversely affect the participant’s ability to participate in the study.
• Any significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of study participation, or, influence the result of the study, or, adversely affect the participant’s ability to participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is determination of midazolam pharmacokinetic (PK) parameters (clearance, volume of distribution and half life) in critically ill children and in otherwise healthy children undergoing surgery. The PK parameters modelled on study data will be used to test whether midazolam pharmacokinetics are significantly different in these two populations. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation of PK parameters will be done at the end of the trial. |
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E.5.2 | Secondary end point(s) |
(a) Whether measurement of midazolam levels using microvolume
samples of dried blood is equivalent to midazolam measurements made using wet blood samples.
(b) How well ‘Symcyp Paediatric Simulator’ (SPS) predicts midazolam pharmacokinetic(PK) parameters (clearance, volume of distribution and half life) in critically ill children and in otherwise healthy children undergoing surgery.
Symcyp Paediatric Simulator predictions of midazolam PK parameters will be classed on how close they are to PK parameter estimates modelled using study data. Predictions that fall between 0.8 and 1.25 fold of the modelled PK parameters will be classed as very good; predictions that fall between 1.25 and 2 fold will be classed as fair and
predictions greater than 2 fold will be classed as poor. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation of secondary end points will be done at the end of the trial. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 30 |