Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Clonidine is widely used off-label in children for several indications. Clonidine is used for treatment and/or prevention of postoperative agitation in children anaesthetised with Sevoflurane. The investigators don´t have solid evidence for the effect and the investigators don´t have data for characterization of the pharmacokinetic profile among age-groups for children 1-6 years.
In this study the investigators want to investigate if IV Clonidine administered at the end of surgery can prevent/reduce postoperative agitation. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including a 30-day follow-up.
BACKGROUND:
Clonidine is widely used off-label in children for several indications such as treatment and/or prevention of postoperative agitation when anaesthetised with Sevoflurane. However, the current level of evidence in support of Clonidine treatment for postoperative agitation in children remains limited. In addition, the pharmacokinetic profile of intravenous Clonidine in children is not well characterized for age-groups.
METHODS/DESIGN:
In this prospective multicentre double-blinded randomized clinical trial, the investigators aim to investigate the impact of intravenous (IV) Clonidine administered at the end of surgery, on the incidence and degree of postoperative agitation. Children will be assigned to either the intervention or the placebo group. The allocation will be carried out centrally and stratified based on age and trial-site, with152 patients allocated to each group. In the intervention group, 3 micrograms per kg of IV clonidine is administered approximately 20 minutes before the expected completion of the surgery (as assessed by the surgeon). In the control group; Saline (placebo) is injected in equal quantity during surgery at the same time. The drugs are concealed in identical blinded ampoules.
The primary outcome is postoperative agitation measured on the Watcha scale. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including 30-day follow-up.
Twenty of the patients age 1-2 years and twenty age >2 years, with a peripheral venous access in place, will be allocated to drug assay sampling; enabling a compartmental PK analysis based on age group, using non-linear mixed effects models.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | Clonidine : injection og 3 micg/kg IV during the operation. |
|
| Placebo | Placebo Comparator | Placebo : injection og equal amount of NaCl IV during the operation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clonidine | Drug | Injection - during surgery |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative Agitation | Measured by Watchae Scale (score 1-4), scores 1-2 = no agitation and scores 3-4 = agitated | 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| Fentanyl and Morphine Requirements | Amount used | Recorded during the stay in the postoperative recovery room |
| Pain Assessment | Pain score used: FLACC score = Face, Legs, Activity, Cry, Consolability Score ranges from 0 to 10 (severity increases with increasing score) Pain is FLACC score more than 3 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Steen Henneberg, MD, DMSc | Rigshospitalet, Denmark | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet | Copenhagen | Region Sjælland | 2100 | Denmark | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24727829 | Background | Pickard A, Davies P, Birnie K, Beringer R. Systematic review and meta-analysis of the effect of intraoperative alpha(2)-adrenergic agonists on postoperative behaviour in children. Br J Anaesth. 2014 Jun;112(6):982-90. doi: 10.1093/bja/aeu093. Epub 2014 Apr 11. | |
| 30169192 | Derived | Ydemann M, Nielsen BN, Henneberg S, Jakobsen JC, Wetterslev J, Lauritsen T, Steen N, Edstrom B, Afshari A; PREVENT AGITATION Research Group. Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial. Lancet Child Adolesc Health. 2018 Jan;2(1):15-24. doi: 10.1016/S2352-4642(17)30127-X. Epub 2017 Nov 2. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Intervention | Clonidine : injection og 3 micg/kg IV during the operation. Clonidine: Injection - during surgery |
| FG001 | Placebo | Placebo : injection og equal amount of NaCl IV during the operation. Placebo: Injection - during surgery |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Intervention | Clonidine : injection og 3 micg/kg IV during the operation. Clonidine: Injection - during surgery |
| BG001 | Placebo | Placebo : injection og equal amount of NaCl IV during the operation. Placebo: Injection - during surgery |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Postoperative Agitation | Measured by Watchae Scale (score 1-4), scores 1-2 = no agitation and scores 3-4 = agitated | 9 were excluded in the primary outcome due to missing data points | Posted | Number | participants with agitation | 1 day |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention | Clonidine : injection og 3 micg/kg IV during the operation. Clonidine: Injection - during surgery |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Re-bleeding | Surgical and medical procedures | Systematic Assessment | events leading to admission |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Opioid-related side-effects | General disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mogens Ydemann, MD | Rigshospitalet | +45 35455620 | mogens@ydemann.dk |
Not provided
| ID | Term |
|---|---|
| D011595 | Psychomotor Agitation |
| ID | Term |
|---|---|
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D011596 | Psychomotor Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D003000 | Clonidine |
| ID | Term |
|---|---|
| D048288 | Imidazolines |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Injection - during surgery |
|
|
| recovery room - hours |
| First Administration of Fentanyl or Morphine | Time to administration | recovery room |
| Adverse Events | from intervention to discharge from the recovery room |
| Køge Sygehus, Anæstesiologisk Afdeling |
| Køge |
| 4600 |
| Denmark |
| Anæstesiologisk afdeling, Vejle Sygehus | Vejle | 7100 | Denmark |
| 27264945 | Derived | Ydemann M, Nielsen BN, Wetterslev J, Henneberg S, Lauritsen T, Steen N, Edstrom B, Afshari A. Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial. Dan Med J. 2016 Jun;63(6):A5234. |
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Fentanyl and Morphine Requirements | Amount used | Posted | Mean | Standard Deviation | mg morphine equivalents | Recorded during the stay in the postoperative recovery room |
|
|
|
| Secondary | Pain Assessment | Pain score used: FLACC score = Face, Legs, Activity, Cry, Consolability Score ranges from 0 to 10 (severity increases with increasing score) Pain is FLACC score more than 3 | Posted | Mean | Standard Deviation | Pain Score | recovery room - hours |
|
|
|
| Secondary | First Administration of Fentanyl or Morphine | Time to administration | Posted | Median | Standard Deviation | MEDIAN time (min) to administration | recovery room |
|
|
|
| Secondary | Adverse Events | Posted | Number | participants | from intervention to discharge from the recovery room |
|
|
|
| 0 |
| 191 |
| 2 |
| 191 |
| 0 |
| 191 |
| EG001 | Placebo | Placebo : injection og equal amount of NaCl IV during the operation. Placebo: Injection - during surgery | 0 | 188 | 2 | 188 | 5 | 188 |
|
| Late arrival in the postoperative care unit | General disorders | Systematic Assessment | events leading to admission |
|
| Pale and not drinking and eating | General disorders | Systematic Assessment | events leading to admission |
|
| PONV | Gastrointestinal disorders | Systematic Assessment | events leading to admission |
|
| Laryngeal spasm | General disorders | Systematic Assessment |
|
| Prolonged anaesthesia | General disorders | Systematic Assessment |
|
Not provided
Not provided
| D019954 |
| Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000096762 | Aberrant Motor Behavior in Dementia |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D006571 |
| Heterocyclic Compounds |
| Treated for low blood pressure |
|