sedation in intensive care MedDRA version: 18.1 Level: PT Classification code 10039897 Term: Sedation System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: CLONIDINE HYDROCHLORIDE
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: clonidine hydrochloride
CAS Number: 4205-91-8
Sponsors
Universitätsklinikum Erlangen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or Female - Aged from birth (=34 weeks gestational age [GA]) to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Body weight less than 1200 g - Gestational age [GA] of <34 weeks - Body weight 3 kg or less AND aged 28 days or older - Body weight less than 10 kg AND aged 2 years old or older - Body weight greater than 85 kg. - Subjects who will be 18 years old in less than 3 weeks - Subjects who have already received clonidine as a sedative agent within the last 7 days prior to admission to PICU - Known hypersensitivity to the IMP (Clonidine) or comparator (Midazolam), or NIMP (Morphine, Propofol) or any of their formulation ingredients and their rescue medication - Subjects being treated with concomitant medications - Subjects less than 24 hours post-resuscitation - Subjects who have been under sedation for more than 72 hours immediately prior to assessment - Subjects currently being treated with continuous positive airway pressure (CPAP) - Subjects currently being treated with Extra Corporeal Membrane Oxygenation (ECMO) - Subjects with treatment-induced whole body hypothermia - Subjects with severe organ insufficiencies - Subjects with traumatic brain injury all grades (due to potential effects on the level of consciousness). - Subjects with intracranial pathology (tumour, haemorrhage, infections) with an effect on level of consciousness. - Subjects with severe mental retardation with or without a well-defined syndrome that preclude performance of a COMFORT-B Score. - Subjects with Myasthenia gravis, Spinal muscular atrophy, or other rare neurologic diseases and conditions which that preclude performance of a COMFORT-B Score. - Subjects with major congenital anomalies of the central nervous system - Subjects with phaeochromocytoma. - Subjects with severe bradyarrhythmia resulting from either sick-sinus syndrome or AV block of 2nd or 3rd degree. - Subjects with current status epilepticus or active fitting (2 or more seizures regularly on a daily basis) at admission. - Subjects with acute asthma. - Subjects with paralytic ileus. - Known arterial hypertension requiring chronic treatment in medical history. - Females who are pregnant, lactating or planning to become pregnant or who return a positive result to a urine pregnancy test. - Employee or direct relative of an employee or any member of the study site staff or the Sponsor/ study management staff (applies to subject and/ or subject’s parent(s). - Participation in a clinical intervention study using drugs within the last 3 weeks - Previous participation in this clinical study at any time.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the non-inferiority of the sedative properties of continuous intravenous (i.v.) clonidine compared to continuous i.v. midazolam in mechanically ventilated children and adolescents (0 - <18 years) admitted to a paediatric intensive care unit (PICU).; Secondary Objective: - To evaluate the safety and tolerability (including withdrawal effects) of clonidine compared with midazolam in ventilated children and adolescents admitted to PICU. - To determine clonidine dose-dependent effects on sedation. - To establish the pharmacokinetics - pharmacodynamics (PK-PD) relationship of clonidine for sedation in PICU. - To compare the cumulative total morphine consumption/kg between the two arms in the first 48 hours of investigational medical product (IMP) administration. - To determine if candidate genes predict adequate response to clonidine and midazolam in critically ill paediatric patients. - To identify polymorphisms of clinical relevance to the sedative action of clonidine, midazolam and morphine. - To correlate midazolam pharmacokinetics to polymorphisms of candidate genes. - To correlate clonidine pharmacokinetics to polymorphisms of candidate genes. -To correlate morphine pharmacokinetics to polymorphisms of candidate genes. ;Primary end point(s): proportion of subjects receiving clonidine with sedation failure compared to those subjects receiving midazolam;Timepoint(s) of evaluation of this end point: Sedation and pain assessed at: baseline/ randomization, treatment period, completion visit, post dose monitoring for up to 24 hours. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Primary PK parameters: clearance (CL), volume of distribution (VD) and inter-compartmental clearance (Q), Cmax, AUC, t1/2, Csteady state, Ctrough. • PKPD modeling. • PKPD covariate model • Safety and tolerability assessments • Extent of withdrawal effects. • The extent of delirium. • Rebound hypertension. • Percentage of respiratory depression per group. • Adverse event reporting of symptoms indicative of post-ICU stress. • Neurodevelopment. • CYP3A4, CYP3A5, CYP2D6, COMT, OPRM1, OCT1 and UGT2B7 polymorphisms (additional polymorphisms are listed in protocol). ; Timepoint(s) of evaluation of this end point: • PK parameters: treatment period, completion visit, post dose monitoring. • Safety and tolerability assessments: treatment period, completion visit, post dose monitoring, follow up (14 days post final dose and 1 year post final dose [neonates only]). • Extent of withdrawal effects, including the extent of delirium: treatment period, completion visit, post dose monitoring for at least 24 hours. • Rebound hypertension: for at least 72 hours post cessation of treatment. • Respiratory depression: during re-intubation apnaea in treatment period, completion visit, post dose monitoring every 24 hours. • Neurodevelopment: at 12 months after cessation of IMP (neonates only). • Polymorphisms: On 1 day of treatment period only. | — |
Countries
Czech Republic, Estonia, Germany, Italy, Netherlands, Spain, Sweden
Contacts
Public ContactKinder- und Jugendklinik
Universitätsklinikum Erlangen
Outcome results
None listed