Overview
Sponsor-declared trial summary
Following heart surgery, patients experience poor postoperative pain control and a moderate/high opioid consumptions. This is correlated to adverese events and poor outcome.
The primary objective of this trial is to investigate the efficacy of a single‐dose of Intraoperative methadone, administered after induction of anesthesia, compared to administration of fentanil and oxycodone per-operatively (usual care), on the endpoint postoperative opioid consumption in adult subjects undergoing el…
Key facts
- Sponsor
- Rigshospitalet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03], Diseases [C] - Cardiovascular Diseases [C14]
- Decision date (initial)
- 2025-01-10
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-519224-24-00
- EudraCT number
- 2022-000077-57
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
The primary objective of this trial is to investigate the efficacy of a single‐dose of Intraoperative methadone, administered after induction of anesthesia, compared to administration of fentanil and oxycodone per-operatively (usual care), on the endpoint postoperative
opioid consumption in adult subjects undergoing elective or subacute CABG and/or valve surgery.
Secondary objectives 1
- The secondary objectives of this trial are to investigate the efficacy of the intervention on patient reported outcomes including pain intensity, quality of recovery and patient satisfaction, as well as effect on safety endpoints.
Conditions and MedDRA coding
Following heart surgery, patients experience poor postoperative pain control and a moderate/high opioid consumptions. This is correlated to adverese events and poor outcome.
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Methadone versus fentanil and oxycodone for post-operative pain reduction This study is a randomized placebo-controlled, assessor- and participant-blinded trial. The study will be initiated at the tertiary heart center at Copenhagen University hospital, Rigshospitalet. Participants will be randomized in a 1:1 ratio to either methadone or usual care consisting of fentanil and oxycodone.
|
Randomised Controlled | Double | [{"id":94007,"code":4,"name":"Analyst"},{"id":94008,"code":5,"name":"Carer"},{"id":94005,"code":2,"name":"Investigator"},{"id":94006,"code":3,"name":"Monitor"},{"id":94004,"code":1,"name":"Subject"}] | methadone group: The methadone group will receive a fixed dose of methadone of 0.3mg/kg administered after induction of anesthesia. usual care group: The usual care group will receive a fentanil 15 mcg/kg at induction of anesthesia plus oxycodone 0.2mg/kg approximately 30 minutes prior to end of surgery. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- 1) Age ≥ 18 years 2) Scheduled for CABG and/or valve surgery.
Exclusion criteria 1
- 1) Acute surgery 2) Pregnancy or currently breastfeeding 3) Know elongated Qt syndrome 4) Prolonged QT‐interval assessed by electrocardiogram > 500ms 5) Existing treatment with methadone 6) Preadmission treatment with opioids 7) Allergy to methadone 8) Inability to provide informed consent 9) Dialysis There will be no general restrictions on inclusion into other
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint will be cumulated intravenous morphineequivalent consumption within 48 hours from surgery
Secondary endpoints 12
- Intraoperative need for inotropes and vasopressors
- Pain intensity assessed by the Numeric Rating Scale (NRS) at rest and at cough.
- Pain intensity assessed by the Numeric Rating Scale (NRS) during physiotherapeutic testing
- Time from arrival in CICU until patient extubating and mobilization.
- CICU Length of stay (time from arrival at CICU until booking of transfer to the ward)
- Days until bowel function (movement, Flatus, stool)
- Quality of Recovery 1516 at postoperative day 0, 1, 2, 3, 30 and 90.
- Quality of life assessed by the SF-3617 after 90 days.
- Chronic pain assessment at 30 and 90 days after surgery.
- Time to hospital discharge.
- 3 months mortality
- Reported occurrence of postoperative arrythmias
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP101887829 · ATC
- Active substance
- Methadone Hydrochloride
- Substance synonyms
- DL-6-DIMETHYLAMINO-4,4-DIPHENYL-3-HEPTANONE HYDROCHLORIDE, (±)-METHADONE HYDROCHLORIDE, PHENADONE HYDROCHLORIDE
- Route of administration
- SOLUTION FOR INJECTION
- Max daily dose
- 0.3 mg/kg milligram(s)/kilogram
- Max total dose
- 0.3 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N07BC02 — METHADONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 2
Fentanyl "B. Braun" 50 mikrogram/ml injektionsvätska, lösning
PRD569618 · Product
- Active substance
- Fentanyl Citrate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 1 mg/Kg milligram(s)/kilogram
- Max total dose
- 1 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N01AH01 — FENTANYL
- Marketing authorisation
- 30620
- MA holder
- B.BRAUN MELSUNGEN AG
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Lindoxa, injektions-/infusionsvæske, opløsning
PRD6278222 · Product
- Active substance
- Oxycodone Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 12 mg/Kg milligram(s)/kilogram
- Max total dose
- 12 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N02AA05 — OXYCODONE
- Marketing authorisation
- 59380
- MA holder
- 2CARE4 GENERICS APS
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Natriumklorid isotonisk "SAD", injektionsvæske, opløsning
PRD349415 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 10 ml millilitre(s)
- Max total dose
- 10 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
- Marketing authorisation
- 16404
- MA holder
- AMGROS I/S
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
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
- Mark Soegaard Niegsch
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Mark Soegaard Niegsch
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Authorised, recruitment pending | 220 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2022-000077-57 | 5,2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_ICF adults | 1 |
| Subject information and informed consent form (for publication) | L1_SIS adults | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Fentanyl B Braun | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Lindoxa | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Methadon Streuli_FI_DE | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-12-16 | Denmark | Acceptable 2025-01-06
|
2025-01-10 |