Prospective, multicentre, randomised, double-blinded and placebo-controlled clinical trial on the efficacy and safety of clonidine as a co-medication in analgesia and sedation of long-term-ventilated neonates and infants

ISRCTN	ISRCTN77772144
DOI	https://doi.org/10.1186/ISRCTN77772144
Secondary identifying numbers	N/A

Submission date: 10/07/2003
Registration date: 20/01/2004
Last edited: 07/04/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Neonatal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Prof Bernhard Roth
Scientific

Joseph-Stelzmann-Str. 9
Cologne
50931
Germany

Study information

Study design	Multicentre randomised double-blind placebo-controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Prospective, multicentre, randomised, double-blinded and placebo-controlled clinical trial on the efficacy and safety of clonidine as a co-medication in analgesia and sedation of long-term-ventilated neonates and infants
Study hypothesis	PAED-Net (P-N) is a corporation of clinical trial coordination centers (KKS) with specific paediatric sections at 6 German universities. The coordinating center of P-N is located at the KKS in Mainz (Prof. Dr. F. Zepp). The intention of P-N is to improve pharmacological trials in childhood according to GCP/ICH. The proposed study is financed by the BMBF with the aim to demonstrate the successful cooperation of the P-N. Scientific background: A long-term mechanical ventilation of neonates and infants under medical and ethical aspects is only possible with adequate analgesia and sedation usually by opioids, barbiturates and benzodiazepines. The use of these agents can be complicated by adverse events, tolerance and physical dependence. Clonidine (C) is a centrally acting alpha2-agonist with analgesic and hypnotic properties. By a sympatolysis, C suppresses physical withdrawal-symptoms. There is preliminary data showing a possible benefit of C in reducing the dosage of opioids and other centrally-acting agents as well as in reducing the withdrawal-symptoms after cessation of these agents [1]. Preliminary data exists, demonstrating cardiovascular stability in children undergoing heart-surgery and receiving C (1 µg/kg/h) [2]. Aim: Reduction of the consumption of fentanyl, midazolame and thiopentone (mg/kg) beginning with infusion of C or placebo (4th day of ventilation) over 3 days. Reduction of withdrawal-symptoms. Pharmacokinetics of C.
Ethics approval(s)	Not provided at time of registration.
Condition	Long-term ventilated infants
Intervention	Clonidine (1 µg/kg/h) or placebo is given with the 4th day of ventilation. Analgesics and sedatives are fentanyl, midazolame and thiopentone. Following cessation of analgesics and sedatives, clonidine is reduced stepwise.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Clonidine, fentanyl, midazolame and thiopentone
Primary outcome measure	A positive confirmation of the hypothesis can lead to an extension of the licensing of C by the manufacturer. Implementation of C in the therapy of long-term ventilated newborns and infants by implementation of the results in the guidelines of the medical societies is desirable. A successful performance of the study is intended to ameliorate the situation of pharmacological trials in childhood in Germany by extension of the infrastructure of the P-N.
Secondary outcome measures	Not provided at time of registration.
Overall study start date	31/07/2003
Overall study end date	31/12/2006

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	Both
Target number of participants	210
Participant inclusion criteria	Term-newborns, infants ≤24th month of life. Expected duration of ventilation: 6 days.
Participant exclusion criteria	1. Any contraindication to clonidine application: 1.1 Hypotone, catecholamine and volume-refractory circulation problems 1.2 Dysfunction of cardiac excitation, like atrioventricular blocks second and third degree, sick sinus syndrome 1.3 Relevant circulation-effective bradycardias 1.4 Hypersensitivity against clonidine or any other component of the drug 2. Any circumstances, which make the evaluation of pain sensation impossible (for example coma, severe brain injury, hypoxic-ischemic brain injury, neurological or neuromuscular illnesses, application of muscle relaxants (except short-time application for intubation and application at the first day of ventilation) 3. Newborns: anamnestic evidence for drug abuse of the mother (for example psychopharmaca, opioids)
Recruitment start date	31/07/2003
Recruitment end date	31/12/2006

Locations

Countries of recruitment

Germany

Study participating centre

University Hospital of Cologne

Cologne
50931
Germany

Sponsor information

University Hospital of Cologne (Germany)
Hospital/treatment centre

Joseph-Stelzmann-Str. 9
Cologne
50931
Germany

"ROR"	https://ror.org/05mxhda18

Funders

Funder type

Industry

Federal Ministry of Education and Research (Germany)
Government organisation / National government

Alternative name(s): Federal Ministry of Education and Research, BMBF
Location: Germany

Boehringer Ingelheim (Germany)
Private sector organisation / For-profit companies (industry)

Alternative name(s): Boehringer Ingelheim Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH, BI, BIPI
Location: United States of America

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/07/2014		Yes	No