Opioid UsePhase 4AFFECT2NCT05639712
Affective Effects of Pre-surgery Opioids: a Randomized, Doubleblind Placebo-controlled Trial
A Phase 4 study testing Morphine 2.5 mg i.v., Morphine 5 mg i.v. and Morphine 10 mg i.v. in people with Opioid Use and Affective Symptoms, run by Oslo University Hospital at 1 site in Norway.
Trial summary
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. Charting opioid use after surgery in patients treated at hospitals in Norway 3. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid Use, Affective Symptoms
- What is being tested?
- Morphine 2.5 mg i.v., Morphine 5 mg i.v. and Morphine 10 mg i.v.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,014 participants
- Where
- 1 siteNorway
- Study dates
- 13 Dec 2022to 27 Jun 2025
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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,
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- 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.
- Pregnancy. Women of childbearing potential defined as all premenopausal female (a postmenopausal state is defined as no menses for 12 months without an alternative medical cause) will be asked if they are pregnant.
- Breastfeeding women.
- Illegal drugs use like opioids, cocaine and amphetamine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Understanding Opioid Use Before and After Surgery in Norway: A Prospective Multicenter Study and Randomized Double-blind Controlled Study
- 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.
- Charting opioid use after surgery in patients treated at hospitals in Norway
- Identify predictors for postoperative opioid use and persistent pain
Read the detailed description
The aim of the present study is to assess and compare, with a randomized, double-blind placebo-controlled trial, the affective effects of three commonly used opioid analgesics (Morphine, oxycodone and fentanyl) administered in three different doses before surgery in a clinical setting associated with physiological and psychological stress.
As a starting point, we have conducted an observational quality control study on peri-operative opioid pain management in day surgery patients.
Quality control study - a pilot study In this observational quality control study, we measured acute effects of the opioid agonist Remifentanil (effect site concentration 5ng/ml, Minto model) in day surgery patients on the operating table at Kongsberg hospital. Patients rated their levels of "feeling good" and "anxious" on a 0-10 numerical rating scale (NRS) immediately before and 1 minute after receiving remifentanil infusion. They also rated drug-specific effects such as "feeling high", "liking the drug effects" and their "level of drug-related discomfort". Moreover, we collected data on postoperative opioid use and pain during recovery through a telephone interview on the day following the surgery. The study was conducted with the usual standard hospital treatment and as such, did not interfere with the patients' medical procedures. All the procedures were approved by the data protection officer at Kongsberg Hospital, and all included patients signed informed consent on the day of surgery.
In the weeks prior to surgery participants received a questionnaire to assess their pain levels, nervousness and demographics as part of the hospital's standard procedure. On the day of surgery, approximately 30 min before surgery (T2) patients were asked to fill in questionnaires to assess mood, pain and prior opioid use. One minute before and one minute after opioid ( administration (T3), the patient was asked to rate mood, anxiety, drug liking and drug related discomfort. On the day following surgery patients were contacted by phone to assess their mood, pain and pain interference, as well as their pain relief strategies in the last 24h (e.g. use of provided analgesics).
160 patients were included in the pilot quality control study. The results of the pilot study show that patients report a clear feeling of 'drug high' after remifentanil infusion. Surprisingly, however, the opioid analgesic induced only a weak reduction of anxiety, and the majority of patients reported feeling worse or equally good, but not better, after the infusion. In the postoperative phone interview, many patients tell us they have not used any of the opioid drugs prescribed for at-home pain relief during the first 24 hours are recovering at home. Stated reasons include a fear of addiction, as well as a wish to keep the analgesics in case of breakthrough/peak pain at a later stage. These preliminary results do not support the opioid pre-induction procedure as an effective manner to produce pre-surgery stress relief. It might be possible that the subjective perception of stress relief does not match the physiological relief reaction to stress.
On the basis of these intriguing, preliminary findings, we will now conduct a more comprehensive randomized double-blind controlled study comparing different classes of pre-surgical opioid analgesics on the subjective and physiological affective reactions in an acute stress clinical situation in Norway.
Possible participants of the AFFECT2 RCT (randomized controlled trial) will also be asked if they wish to join a parallel longitudinal study conducted in collaboration with the University of Oslo (UiO) in which we will collect and analyse data on relevant pre-surgery risk factors for problematic opioid use, and to quantify opioid-induced analgesia before and after surgery using prescription registry data.
- Conditions
- Opioid Use, Affective Symptoms
- Being tested
- Placebo, Morphine 2.5 mg i.v., Morphine 5 mg i.v., Morphine 10 mg i.v., Oxycodone 2.5 mg i.v.
- Medical subject headings
- Affective Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called 0.9% NaCl , Natriumklorid 9 mg/ml, Hameln (ATC code: B05B B01)
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
Morphine 2.5 mg i.v.Drug
Also called Morphine, Orion (ATC code: N02A A01)
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
Morphine 5 mg i.v.Drug
Also called Morphine, Orion (ATC code: N02A A01)
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
Morphine 10 mg i.v.Drug
Also called Morphine, Orion (ATC code: N02A A01)
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
Oxycodone 2.5 mg i.v.Drug
Also called Oxycodone, Hameln (ATC code: N02A A05)
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
Oxycodone 5 mg i.v.Drug
Also called Oxycodone, Hameln (ATC code: N02A A05)
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
Oxycodone 10 mg i.v.Drug
Also called Oxycodone, Hameln (ATC code: N02A A05)
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
Fentanyl 0.025 mg i.v.Drug
Also called Fentanyl, Hameln (ATC code: N01A H01)
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
Fentanyl 0.05 mg i.v.Drug
Also called Fentanyl, Hameln (ATC code: N01A H01)
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
Fentanyl 0.1 mg i.v.Drug
Also called Fentanyl, Hameln (ATC code: N01A H01)
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Fentanyl 0.1 mg i.v. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2-4 minutes
Secondary outcomes (1)
Onset time
Determine onset time of subjective drug effect of the three opioids (each at three different doses) and proportion of participants that report feeling a drug effect within 0-2 minutes
Measured: Subjective onset time of the three opioids during the 2 minutes observation time before anaesthesia induction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start13 Dec 2022
- Primary completion27 May 2025
- Study completion27 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Opioid UseStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,014 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Vestre VikenHF Kongsberg Sykehus
- Responsible party
- Principal investigator, Harald Lenz, Oslo University Hospital
- Investigators
- Gernot Ernst, MD,PhD, Principal investigator, Kongsberg Hospital, Vestre Viken Health Trust Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05639712
- Sponsor's protocol ID
- AFFECT2 Version 2, 04.11.2022
- Other IDs
- 2024-518308-37-00, 2022-002938-13
- Acronym
- AFFECT2
- Status last verified
- Sep 2026
- First submitted
- 17 Nov 2022
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Angst MS, Lazzeroni LC, Phillips NG, Drover DR, Tingle M, Ray A, Swan GE, Clark JD. Aversive and reinforcing opioid effects: a pharmacogenomic twin study. Anesthesiology. 2012 Jul;117(1):22-37. doi: 10.1097/ALN.0b013e31825a2a4e.
PubMed 22713632Astuto, M., & Lauretta, D. (2009). Anesthesia Induction. In M. Astuto (Ed.), Basics (pp. 85-99). Milano: Springer Milan.
Bershad AK, Miller MA, Norman GJ, de Wit H. Effects of opioid- and non-opioid analgesics on responses to psychosocial stress in humans. Horm Behav. 2018 Jun;102:41-47. doi: 10.1016/j.yhbeh.2018.04.009. Epub 2018 Apr 24.
PubMed 29673620Bjerkeset O, Romild U, Smith GD, Hveem K. The associations of high levels of C-reactive protein with depression and myocardial infarction in 9258 women and men from the HUNT population study. Psychol Med. 2011 Feb;41(2):345-52. doi: 10.1017/S0033291710000887. Epub 2010 May 6.
PubMed 20444310Choudhary P, Dutta A, Sethi N, Sood J, Rai D, Gupta M. Pre-induction fentanyl dose-finding study for controlled hypotension during functional endoscopic sinus surgery. Indian J Anaesth. 2019 Aug;63(8):653-659. doi: 10.4103/ija.IJA_866_18.
PubMed 31462812Colasanti A, Rabiner EA, Lingford-Hughes A, Nutt DJ. Opioids and anxiety. J Psychopharmacol. 2011 Nov;25(11):1415-33. doi: 10.1177/0269881110367726. Epub 2010 Jun 8.
PubMed 20530588Courtwright, D. T. (2001). Dark Paradise: A History of Opiate Addiction in America. Cambridge MA: Harvard University Press.
Dale O, Moksnes K, Kaasa S. European Palliative Care Research Collaborative pain guidelines: opioid switching to improve analgesia or reduce side effects. A systematic review. Palliat Med. 2011 Jul;25(5):494-503. doi: 10.1177/0269216310384902.
PubMed 21708856Deighton S, Neville A, Pusch D, Dobson K. Biomarkers of adverse childhood experiences: A scoping review. Psychiatry Res. 2018 Nov;269:719-732. doi: 10.1016/j.psychres.2018.08.097. Epub 2018 Aug 25.
PubMed 30273897Doleman B, Leonardi-Bee J, Heinink TP, Bhattacharjee D, Lund JN, Williams JP. Pre-emptive and preventive opioids for postoperative pain in adults undergoing all types of surgery. Cochrane Database Syst Rev. 2018 Dec 3;12(12):CD012624. doi: 10.1002/14651858.CD012624.pub2.
PubMed 30521692Drewes AM, Jensen RD, Nielsen LM, Droney J, Christrup LL, Arendt-Nielsen L, Riley J, Dahan A. Differences between opioids: pharmacological, experimental, clinical and economical perspectives. Br J Clin Pharmacol. 2013 Jan;75(1):60-78. doi: 10.1111/j.1365-2125.2012.04317.x.
PubMed 22554450Dutta A, Sethi N, Choudhary P, Sood J, Panday BC, Chugh PT. The impact of preinduction fentanyl dosing strategy on postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy. J Opioid Manag. 2018 Jul/Aug;14(4):283-293. doi: 10.5055/jom.2018.0460.
PubMed 30234925Evans SM, Foltin RW, Levin FR, Fischman MW. Behavioral and subjective effects of DN-2327 (pazinaclone) and alprazolam in normal volunteers. Behav Pharmacol. 1995 Mar;6(2):176-186.
PubMed 11224325Garland EL, Froeliger B, Zeidan F, Partin K, Howard MO. The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways. Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2597-607. doi: 10.1016/j.neubiorev.2013.08.006. Epub 2013 Aug 26.
PubMed 23988582Helsedirektoratet. (2018). Utvikling og variasjon i kirurgisk behandling 2013-2017. Retrieved from Oslo: