Efficacy, Safety and Pharmacokinetic Study of Intravenous Clonidine Versus Midazolam for Sedation in Paediatric Patients

NCT ID: NCT02509273

Last Updated: 2019-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2018-10-22

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Closed1 aims to compare the efficacy, safety and pharmacokinetics of clonidine (hydrochloride) to midazolam in the sedation of ventilated children and adolescents (0-18 years) admitted to a paediatric intensive care unit (PICU) and requiring mechanical ventilation and sedation for at least 24 hours.

In particular, the proportion of subjects with sedation failure at the maximum possible dose (defined within the study protocol) will be measured. Additionally, the safety and tolerability (including withdrawal effects) of clonidine compared to midazolam will be evaluated. A pharmacokinetic-pharmacodynamic relationship of clonidine for sedation in PICU will be established. Genetic polymorphisms of clinical relevance affecting pharmacokinetics, pharmacodynamics and metabolism will be also identified.

Ad hoc paediatric parenteral formulations of clonidine hydrochloride and midazolam will be manufactured. At least 300 subjects will be enrolled from study centres in five European member countries (Czech Republic, Germany, Italy, the Netherlands, and Sweden).

The clinical study will enrol critically ill paediatric patients who require mechanical ventilation and sedation.

Subjects will be closely followed using standard PICU monitoring of vital functions (continuous assessment of heart rate and peripheral arterial oxygen saturation, intermittent assessment of systolic and diastolic blood pressure), intermittent assessment of pain and depth of sedation, documentation of parameters of mechanical ventilation and intermittent arterial blood gas analysis.

The study will be conducted in compliance with the study protocol, Good Clinical Practice (ICH-GCP) and the applicable regulatory requirement(s). In addition, qualified PICU staff will be monitoring subjects around the clock, thus minimising reaction time in case of alarms or deterioration of clinical parameters.

This project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement n° 602453.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Sedation in Intensive Care

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CLONIDINE HYDROCHLORIDE

solution for i.v. infusion (maximum 55 μg/kg per day; maximum 7 day treatment)

Group Type EXPERIMENTAL

Clonidine

Intervention Type DRUG

MIDAZOLAM

solution for i.v. infusion (maximum 5.5 mg/kg per day; maximum 7 day treatment)

Group Type ACTIVE_COMPARATOR

Midazolam

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Clonidine

Intervention Type DRUG

Midazolam

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Male or Female
* Aged from birth (≥34 weeks gestational age \[GA\]) to \<17 years, 11 months, 1 week old
* Admitted or expected to be admitted (post-operatively) to PICU
* Existing or expected indication for invasive or non-invasive ventilation (except Continuous Positive Airway Pressure, CPAP)
* Anticipated need for continuous sedation for at least 24 hours
* Informed consent (or deferred consent) obtained from the subject's parent(s) or legal guardian(s)
* Where applicable, assent obtained from the subject to participate in the clinical trial

Exclusion Criteria

* Body weight less than 1500 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
* Known hypersensitivity to the IMP (clonidine) or comparator (midazolam), or Non Investigational Medicinal Product (morphine, propofol) or any of their formulation ingredients and their rescue medication
* Subjects anticipated to be treated with forbidden concomitant medications during IMP administration
* 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 Extra Corporeal Membrane Oxygenation (ECMO)
* Subjects with treatment-induced whole body hypothermia
* Subjects with severe organ insufficiencies
* Subjects whose condition is assessed by the investigator to have an effect on the level of consciousness which impairs the assessment of sedation (COMFORT-B/NISS)
* Subjects with phaeochromocytoma
* Subjects with severe bradyarrhythmia resulting from either sick-sinus syndrome or atrioventricular (AV) block of 2nd or 3rd degree
* 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 (a dipstick and serum pregnancy test will be performed at the screening visit).
* 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
* Parent(s)/ legal guardian(s) decline to give informed consent. If parent(s)/ legal guardian(s) are not present
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Erasmus Medical Center

OTHER

Sponsor Role collaborator

University of Tartu

OTHER

Sponsor Role collaborator

Therakind Ltd

UNKNOWN

Sponsor Role collaborator

Gianni Benzi Pharmacological Research Foundation

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role collaborator

Univerzita Karlova v Praze

OTHER

Sponsor Role collaborator

Vereniging Samenwerkende Ouder- En Patientenorganisaties

UNKNOWN

Sponsor Role collaborator

Bambino Gesù Hospital and Research Institute

OTHER

Sponsor Role collaborator

European Commission

OTHER

Sponsor Role collaborator

ARNAS Civico Di Cristina Benfratelli Hospital

OTHER

Sponsor Role collaborator

Servicio Madrileño de Salud, Madrid, Spain

OTHER

Sponsor Role collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Univerzita Karlova v Praze

Prague, , Czechia

Site Status

Tallinn Children's Hospital

Tallinn, , Estonia

Site Status

University of Erlangen-Nürnberg Medical School

Erlangen, , Germany

Site Status

Diakonie Neuendettelsau - Cnopf'sche Kinderklinik Nürnberg

Nuremberg, , Germany

Site Status

Azienda Ospedaliero Universitaria Policlinico di Bari

Bari, , Italy

Site Status

ARNAS Civico Di Cristina Benfratelli

Palermo, , Italy

Site Status

Bambino Gesù Hospital and Research Institute

Rome, , Italy

Site Status

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Karolinska Institutet

Stockholm, , Sweden

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Czechia Estonia Germany Italy Netherlands Spain Sweden

References

Explore related publications, articles, or registry entries linked to this study.

Neubert A, Baarslag MA, Dijk MV, Rosmalen JV, Standing JF, Sheng Y, Rascher W, Roberts D, Winslade J, Rawcliffe L, Hanning SM, Metsvaht T, Giannuzzi V, Larsson P, Pokorna P, Simonetti A, Tibboel D; CLOSED Consortium. The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial. BMJ Open. 2017 Jun 21;7(6):e016031. doi: 10.1136/bmjopen-2017-016031.

Reference Type DERIVED
PMID: 28637741 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2014-003582-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLON01

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.