A double blind, randomised, multicentre, active controlled, parallel-group, phase III trial to evaluate the efficacy, safety and pharmacokinetics of clonidine (hydrochloride) for sedation in children from birth to less than 18 years of age

A double blind, randomised, multicentre, active controlled, parallel-group, phase III trial to evaluate the efficacy, safety and pharmacokinetics of clonidine (hydrochloride) for sedation in children from birth to less than 18 years of age - CloSed

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON42245

Enrollment

150

Registered

2015-06-15

Start date

2016-11-23

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

sedatie Sedation

Interventions

Clonidine as sedative with midazolam as active control.

Clonidine

Paediatric Intensive Care

Sedation

Eligibility

Age

2 Years to 17 Years

Inclusion criteria

Inclusion criteria: Male or female aged from birth >34 weeks gestational age [GA] to

Exclusion criteria

Exclusion criteria: Body weight less than 1200g and/ or gestational age of less than 34 weeks. Body weight greater than 85kg. Subjects under sedation for more than 72 hours Post-resuscitation less than 24 hours. Severe organ insufficiency Abnormalities of the central nervous system impairing the judgement of sedation Acute asthma Known hypersensitivity to (non-)investigational medical products Treatment on ECMO Relatives to investigators or employees of study site No informed consent obtained

Design outcomes

Primary

Measure	Time frame
The primary endpoint is defined as sedation failure within the study treatment period (a maximum of seven days). Sedation failure is defined as: When a subjects assessment results are: Numerical Rating Scale (NRS) score 22 OR Numerical Rating Scale (NRS) score =11 AND Nurses Interpretation of Sedation (NISS) score 1 at a point during the study where no further increase in IMP dose is permitted as described in the dose escalation scheme.	—

Measure

Time frame

The primary endpoint is defined as sedation failure within the study treatment period (a maximum of seven days). Sedation failure is defined as: When a subject*s assessment results are: Numerical Rating Scale (NRS) score 22 OR Numerical Rating Scale (NRS) score =11 AND Nurse*s Interpretation of Sedation (NISS) score 1 at a point during the study where no further increase in IMP dose is permitted as described in the dose escalation scheme.

—

Secondary

Measure	Time frame
* Primary PK parameters estimated will be clearance (CL), volume of distribution (VD) and inter-compartmental clearance (Q). Additional parameters include Cmax, AUC, t1/2, Csteadystate, Ctrough. PK measurements will be made using sparse opportunistic sampling. * PK-PD modelling will seek to elucidate the relationship between IMP pharmacokinetics and sedation as measured by COMFORT-B score. * The PK-PD covariate model will include demographics (e.g. age, weight), clinical characteristics (e.g. reason for admission) and pharmacogenomics (see Genetic parameters in Section 4.3.1) * General safety and tolerability assessments * Extent of withdrawal effects using the Sophia Observation withdrawal Symptoms- Paediatric Delirium (SOS-PD) scale measured three times a day in subjects who receive sedatives and/or opioids for 5 days or more and after cessation of treatment in all subjects for at least 24 hours after treatment. * The extent of delirium measured by the SOS-PD scale. * Rebound hypertension monitored for at least 72 hours post cessation of treatment. * Percentage of respiratory depression per group. * Adverse event reporting of symptoms indicative of post-ICU stress (e.g. nightmares, confusion, hallucinations). * Neurodevelopment of subjects recruited in lower age group (from birth to 27 days)	—

Measure

Time frame

* Primary PK parameters estimated will be clearance (CL), volume of distribution (VD) and inter-compartmental clearance (Q). Additional parameters include Cmax, AUC, t1/2, Csteadystate, Ctrough. PK measurements will be made using sparse opportunistic sampling. * PK-PD modelling will seek to elucidate the relationship between IMP pharmacokinetics and sedation as measured by COMFORT-B score. * The PK-PD covariate model will include demographics (e.g. age, weight), clinical characteristics (e.g. reason for admission) and pharmacogenomics (see Genetic parameters in Section 4.3.1) * General safety and tolerability assessments * Extent of withdrawal effects using the Sophia Observation withdrawal Symptoms- Paediatric Delirium (SOS-PD) scale measured three times a day in subjects who receive sedatives and/or opioids for 5 days or more and after cessation of treatment in all subjects for at least 24 hours after treatment. * The extent of delirium measured by the SOS-PD scale. * Rebound hypertension monitored for at least 72 hours post cessation of treatment. * Percentage of respiratory depression per group. * Adverse event reporting of symptoms indicative of post-ICU stress (e.g. nightmares, confusion, hallucinations). * Neurodevelopment of subjects recruited in lower age group (from birth to 27 days)

—

Countries

Czechia, Germany, Italy, Netherlands, Sweden

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)