Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Temporarily halted
Participants planned
336
Countries
1
Sites
1
Emergence agitation after anaesthesia
To evaluate the efficacy of clonidine for prevention of emergence agitation To describe the pharmacokinetic parameters of clonidine when administered as a single dose intraoperatively
Key facts
- Sponsor
- Rigshospitalet
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11]
- Trial duration
- 22 Oct 2021 → ongoing
- Decision date (initial)
- 2025-01-29
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- The Danish Society of Anaesthesiology and Intensive Care Medicine · The Department of Anaesthesiology, The Juliane Marie Centre, Rigshospitalet
External identifiers
- EU CT number
- 2024-520075-28-01
- EudraCT number
- 2020-005409-26
- ClinicalTrials.gov
- NCT05091242
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Pharmacokinetic, Safety
To evaluate the efficacy of clonidine for prevention of emergence agitation
To describe the pharmacokinetic parameters of clonidine when administered as a single dose intraoperatively
Secondary objectives 3
- To evaluate opioid-sparing effect
- To evaluate postoperative nausea and vomiting
- To evaluate a composite safety outcome
Conditions and MedDRA coding
Emergence agitation after anaesthesia
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 27.1 | PT | 10049989 | Agitation postoperative | 100000004863 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Efficacy and safety, part B Evaluation of efficacy and safety of an intraoperative bolus of intravenous clonidine versus placebo for prevention of emergence agitation in children 3-12 months.
|
Randomised Controlled | Double | [{"id":184731,"code":1,"name":"Subject"},{"id":184734,"code":5,"name":"Carer"},{"id":184733,"code":3,"name":"Monitor"},{"id":184732,"code":2,"name":"Investigator"},{"id":184735,"code":4,"name":"Analyst"}] | Placebo: Intravenous bolus of saline Clonidine: Intravenous bolus of clonidine 3 mcg/kg |
| 2 | Pharmacokinetic, part A Evaluation of pharmacokinetic parameter estimates for an intraoperative intravenous bolus of clonidine in children 3-12 months.
|
2 | None | Clonidine: Intravenous bolus of clonidine 3 mcg/kg |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-520075-28-00 | The PREVENT AGITATION trial II – children ≤1 year | Rigshospitalet |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Paediatric patients (male and female), aged 3- ≤ 12 months
- Scheduled general anaesthesia with sevoflurane and opioid. Induction with propofol is optional
- The legally acceptable representative for the study participant provides written informed consent/assent for the trial
Exclusion criteria 17
- ASA >2
- Cardiac, neuro and trauma surgery
- Ex-premature (<37 weeks)
- Premedication with clonidine
- Intubated prior to scheduled anaesthesia or is expected to require intubation after the procedure
- Critical illness incl. hemodynamic instability (inotropic drugs needed)
- Bleeding requiring transfusion prior to scheduled anaesthesia
- Planned for a postoperative nurse-controlled analgesia pump including a continuous infusion of opioid
- Malignant disease
- Cardiac disease incl. arrhythmia
- Chronic lung disease that may influence study results or study participation in the opinion of the Investigator or may comprise safety and well-being of the patient
- Mental retardation
- Neurological disease including symptoms similar to emergence agitation
- Has or is suspected of having a family or personal history of malignant hyperthermia
- Has or is suspected of having an allergy to study treatment or its excipients
- Any condition that can in opinion of the Investigator, deteriorate safety and well-being of the patients or interfere with pharmacokinetic data
- Positive Covid-19 test or clinical suspicion of Covid-19 (according to current local guidelines)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Emergence agitation measured on the Watcha score (1= calm, 4= agitated and thrashing around)7. The incidence of emergence agitation (Watcha score >2 during stay in the postanaesthetic care unit).
- Pharmacokinetic parameter estimates for compartmental Clearance (CL), Volume of distribution (V) and T½
Secondary endpoints 3
- The amount of additional opioid needed during stay in the postanaesthetic care unit (calculated as morphine equivalents) for treatment of postoperative pain
- No validated scale for assessment of PONV exists and PONV will be assessed by nausea/vomiting Yes or No. While vomiting is obvious, nausea may be considered to be present if the child refuses to eat and other causes are ruled out.
- The proportion of participants with 1) clinically relevant hypotension and, clinically relevant bradycardia, 2) clinically relevant bradycardia and clinically relevant apnoea.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Catapresan 150 mikrogram/ml injektionsvätska, lösning
PRD8603876 · Product
- Active substance
- Clonidine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 3 µg/Kg microgram(s)/kilogram
- Max total dose
- 3 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- C02AC01 — CLONIDINE
- Marketing authorisation
- 8478
- MA holder
- GLENWOOD GMBH
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
SUB12581MIG · Substance
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 2.7 ml millilitre(s)
- Max total dose
- 2.7 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Sodium chloride solution for injection is manufactured and filled in glass ampoules similar to Catapresan solution for injection (test)
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Rigshospitalet
- Sponsor organisation
- Rigshospitalet
- Address
- Blegdamsvej 9
- City
- Copenhagen Oe
- Postcode
- 2100
- Country
- Denmark
Scientific contact point
- Organisation
- Rigshospitalet
- Contact name
- Sponsor's representative Volker Classen
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Study Coordinator Bettina Nielsen
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
| University Hospital Cologne AöR ORG-100012761
|
Cologne, Germany | Laboratory analysis |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Temporarily halted | 286 | 1 |
| Rest of world
Australia
|
— | 50 | — |
Investigational sites
Rigshospitalet
Department of Anaesthesiology, Blegdamsvej 9, 2100, Copenhagen Oe
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2021-10-22 | 2021-10-25 | 2025-11-14 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-132869
- Halt date
- 2025-11-14
- Member states concerned
- Denmark
- Publication date
- 2026-05-07
- Reason
- Medicinal Product related
- Explanation
- The placebo product manufactured by Skanderborg Pharmacy expired on 01-11-2025. Skanderborg Pharmacy had closed their manufacturing facility and extension of shelf-life by the Hospital Pharmacy of the Capital Region was not possible despite positive feedback from the Danish Medicines Agency. Thus, a new manufacturer of the placebo product was required.
- Follow-up measures
- The IMP or placebo product is administered as a single dose in this trial.
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol EU CT 2024-520075-28 | 3 |
| Recruitment arrangements (for publication) | K1_Recruitement arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF part A | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF part B | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Catapresan | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis DK EU CT 2024-520075-28 | 2 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-20 | Denmark | Acceptable 2025-01-27
|
2025-01-29 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-10-09 | Denmark | Acceptable 2025-10-14
|
2025-10-14 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2026-05-11 | Denmark | Acceptable 2026-05-12
|
2026-05-12 |