Affective Effects of Pre-surgery Opioids: a Randomized, Doubleblind Placebo-controlled Trial

NCT05639712 | Completed Phase 4 DMC

• 2 other identifiers: AFFECT2 Version 2, 04.11.20222022-002938-13
• Study Type: interventional
• Target: 1,020
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.To investigate and compare the affective short-term effects of opioid drugs: morphine, oxycodone and fentanyl, administered to the patients before the induction of general anesthesia.
2. 2.Charting opioid use after surgery in patients treated at hospitals in Norway
3. 3.Identify predictors for postoperative opioid use and persistent pain

Conditions

Opioid Use; Affective Symptoms

Outcome Measures

Primary Outcomes (10)

• Anxious

  Asking the patient of feeling anxious; Numeric rating scale 0 -10 prior opioid and post opioid intravenously (or placebo). 0=not anxious and 10=feeling extremely anxious

  8-10 minutes

• Relaxed

  Asking the patient of feeling relaxed. Numeric rating scale 0 -10 prior opioid and post opioid intravenously (or placebo). 0=not relaxed and 10=very relaxed.

  8-10 minutes

• Pain level

  Asking the patient of pain level. Numeric rating scale 0 -10 prior opioid and post opioid intravenously (or placebo). 0=no pain and 10= worst pain imaginable

  8-10 minutes

• Good

  Asking the patient of feeling good. Numeric rating scale 0 -10 prior opioid and post opioid intravenously (or placebo). 0=feeling no good and 10= feeling very good.

  8-10 minutes

• Dizzy

  Asking the patient of feeling dizzy. Numeric rating scale 0-10 post opioid intravenously (or placebo). 0=feeling not dizzy and 10=feeling very dizzy.

  2-4 minutes

• Sedated

  Asking the patient of feeling sedated. Numeric rating scale 0-10 post opioid intravenously (or placebo). 0=feeling not sedated and 10=feeling very sedated.

  2-4 minutes

• Feeling high, Numeric rating scale 0 -10

  Asking the patient of feeling high. Numeric rating scale 0-10 post opioid intravenously (or placebo). 0=feeling not high and 10=feeling very high.

  2-4 minutes

• Euphoric

  Asking the patient of feeling high. Numeric rating scale 0-10 post opioid intravenously (or placebo). 0=feeling not euphoric and 10=feeling very euphoric.

  2-4 minutes

• Drug liking

  Asking the patient of drug liking. Numeric rating scale 0-10 post opioid intravenously (or placebo). 0=feeling not drug liking and 10=feeling very drug liking.

  2-4 minutes

• Drug disliking

  Asking the patient of drug disliking. Numeric rating scale 0-10 post opioid intravenously (or placebo). 0=feeling not drug disliking and 10=feeling very drug disliking.

  2-4 minutes

Other Outcomes (2)

• Heart rate

  10 min

• Heart rate variability

  10 min

Study Arms (10)

Placebo

PLACEBO COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of placebo (0.9% NaCl intravenously). This is carried out on the operating table right before anesthesia

Drug: Placebo

Morphine 2.5 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of morphine 2.5 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Morphine 2.5 mg i.v.

Morphine 5 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of morphine 5 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Morphine 5 mg i.v.

Morphine 10 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of morphine 10 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Morphine 10 mg i.v.

Oxycodone 2.5 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of oxycodone 2.5 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Oxycodone 2.5 mg i.v.

Oxycodone 5 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of oxycodone 5 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Oxycodone 5 mg i.v.

Oxycodone 10 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of oxycodone 10 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Oxycodone 10 mg i.v.

Fentanyl 0.025 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of fentanyl 0.025 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Fentanyl 0.025 mg i.v.

Fentanyl 0.05 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of fentanyl 0.05 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Fentanyl 0.05 mg i.v.

Fentanyl 0.1 mg

ACTIVE COMPARATOR

The patient is given standardized questions about their well-being and affective state before and after the administration of fentanyl 0.1 mg intravenously. This is carried out on the operating table right before anesthesia

Drug: Fentanyl 0.1 mg i.v.

Interventions

Placebo DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of placebo intravenously. This is carried out on the operating table right before anesthesia

Also known as: 0.9% NaCl , Natriumklorid 9 mg/ml, Hameln (ATC code: B05B B01)

Placebo

Morphine 2.5 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of 2.5 mg morphine intravenously. This is carried out on the operating table right before anesthesia

Also known as: Morphine, Orion (ATC code: N02A A01)

Morphine 2.5 mg

Morphine 5 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of morphine 5 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Morphine, Orion (ATC code: N02A A01)

Morphine 5 mg

Morphine 10 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of morphine 10 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Morphine, Orion (ATC code: N02A A01)

Morphine 10 mg

Oxycodone 2.5 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of oxycodone 2.5 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Oxycodone, Hameln (ATC code: N02A A05)

Oxycodone 2.5 mg

Oxycodone 5 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of oxycodone 5 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Oxycodone, Hameln (ATC code: N02A A05)

Oxycodone 5 mg

Oxycodone 10 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of oxycodone 10 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Oxycodone, Hameln (ATC code: N02A A05)

Oxycodone 10 mg

Fentanyl 0.025 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of fentanyl 0.025 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Fentanyl, Hameln (ATC code: N01A H01)

Fentanyl 0.025 mg

Fentanyl 0.05 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of fentanyl 0.05 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Fentanyl, Hameln (ATC code: N01A H01)

Fentanyl 0.05 mg

Fentanyl 0.1 mg i.v. DRUG

The patient is given standardized questions about their well-being and affective state before and after the administration of fentanyl 0.1 mg intravenously . This is carried out on the operating table right before anesthesia

Also known as: Fentanyl, Hameln (ATC code: N01A H01)

Fentanyl 0.1 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Health status ASA1 (American Society of Anesthesiologists physical status) or ASA2 as categorised by a medical doctor at the hospital based on medical history, physical examination, laboratory test etc. unrelated to the current study.
• ASA1 and ASA2 (ASA1 is defined as "Healthy, non-smoking, no or minimal alcohol use" and ASA2 is defined as "Mild diseases only without substantive functional limitations). Being eligible for day surgery means participants are overtly healthy as determined by clinical staff.
• The participant is considered as eligible for the use of fentanyl, morphine and oxycodone by a medical doctor at the hospital, based on an overall assessment of the psychiatric and somatic condition, used medical drugs, regarding possible interactions and contraindications for the use of the study medicaments.
• Body weight and body mass index (BMI) within the range 18-35 kg/m2 (inclusive).
• Capable of giving signed informed consent as which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Having good verbal communication skills in Norwegian.
• Patients undergoing planned day surgery with general anesthesia (outpatient sample).
• Orthopedic, rectal, gynecological, hand and foot surgery, and minor vascular procedures.
• Inpatients undergoing planned gynecological and orthopedic surgery.
• Hysterectomy, laparoscopic ovariectomy, lumbal herniotomy and other related procedures.
• Minor gastrointestinal surgery

You may not qualify if:

• Known allergic reactions to morphine, oxycodone,or fentanyl. Known allergic reactions to any of the incredients described in the SPC, pt 6.1.
• Severe chronic obstructive lung disease,
• Cor pulmonale,
• Severe bronchial asthma,
• Severe respiratory failure with hypoxemia and hypercapnia
• Moderate to severe hepatic impairment,
• Moderate to severe kidney failure
• Acute abdomen
• Increased brain pressure
• Head trauma
• Use of MAO blockers in the last two weeks
• Hypovolemia
• Hypotension
• Myasthenia gravis
• Any other health status not corresponding to ASA1 or ASA2. This includes patients with severe disease burden, major psychiatric disorders that could interfere with the procedures and communication.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Vestre VikenHF Kongsberg Sykehus: collaborator

Study Sites (1)

Harald Lenz

Oslo, Norway

Location

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MeSH Terms

Conditions

Affective Symptoms

Interventions

Morphine; Oxycodone; Fentanyl

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Codeine; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gernot Ernst, MD,PhD

  Kongsberg Hospital, Vestre Viken Health Trust Norway

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization sequences will be generated prior to the first enrolment of the amended protocol by an independent group (Clinical trails unit- OUS) not affiliated with the present study. The drug will be prepared after opening an opaque envelope on the day of surgery by a nurse not participating in the study. The syringe with the drug will be labeled with a code number and handed to the study nurse or doctor.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The patient will be randomized to 1 of 10 arms: Placebo (saline 0.9%), morphine 2.5 - 5 - 10 mg, oxycodone 2.5 - 5 -10 mg, or fentanyl 0.025 - 0.05 - 0.1 mg iv.

Study Record Dates

• First Submitted: November 17, 2022
• First Posted: December 6, 2022
• Study Start: December 13, 2022
• Primary Completion: May 27, 2025
• Study Completion: June 27, 2025
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)