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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05639712
Other study ID # AFFECT2 Version 2, 04.11.2022
Secondary ID 2022-002938-13
Status Recruiting
Phase Phase 4
First received
Last updated
Start date December 13, 2022
Est. completion date December 2025

Study information

Verified date September 2023
Source Oslo University Hospital
Contact Gernot Ernst, MD, PhD
Phone +4748072777
Email bserng@vestreviken.no
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. Identify predictors for postoperative opioid use and persistent pain


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 1000
Est. completion date December 2025
Est. primary completion date December 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: 1. Known allergic reactions to morphine, oxycodone,or fentanyl. Known allergic reactions to any of the incredients described in the SPC, pt 6.1. 2. Severe chronic obstructive lung disease, 3. Cor pulmonale, 4. Severe bronchial asthma, 5. Severe respiratory failure with hypoxemia and hypercapnia 6. Moderate to severe hepatic impairment, 7. Moderate to severe kidney failure 8. Acute abdomen 9. Increased brain pressure 10. Head trauma 11. Use of MAO blockers in the last two weeks 12. Hypovolemia 13. Hypotension 14. Myasthenia gravis 15. 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. 16. 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. 17. Breastfeeding women. 18. Illegal drugs use like opioids, cocaine and amphetamine

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Placebo
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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Locations

Country Name City State
Norway Harald Lenz Oslo

Sponsors (2)

Lead Sponsor Collaborator
Oslo University Hospital Vestre VikenHF Kongsberg Sykehus

Country where clinical trial is conducted

Norway, 

References & Publications (30)

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. — View Citation

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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. — View Citation

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Choudhary 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. — View Citation

Colasanti 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. — View Citation

Courtwright, D. T. (2001). Dark Paradise: A History of Opiate Addiction in America. Cambridge MA: Harvard University Press.

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Drewes 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. — View Citation

Dutta 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. — View Citation

Evans 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. — View Citation

Garland 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. — View Citation

Helsedirektoratet. (2018). Utvikling og variasjon i kirurgisk behandling 2013-2017. Retrieved from Oslo:

Levy N, Mills P. Controlled-release opioids cause harm and should be avoided in management of postoperative pain in opioid naive patients. Br J Anaesth. 2019 Jun;122(6):e86-e90. doi: 10.1016/j.bja.2018.09.005. Epub 2018 Oct 19. No abstract available. — View Citation

Li PH, Ue KL, Wagner A, Rutkowski R, Rutkowski K. Opioid Hypersensitivity: Predictors of Allergy and Role of Drug Provocation Testing. J Allergy Clin Immunol Pract. 2017 Nov-Dec;5(6):1601-1606. doi: 10.1016/j.jaip.2017.03.035. Epub 2017 May 24. — View Citation

Martel MO, Dolman AJ, Edwards RR, Jamison RN, Wasan AD. The association between negative affect and prescription opioid misuse in patients with chronic pain: the mediating role of opioid craving. J Pain. 2014 Jan;15(1):90-100. doi: 10.1016/j.jpain.2013.09.014. Epub 2013 Oct 12. — View Citation

McHugh RK, Weiss RD, Cornelius M, Martel MO, Jamison RN, Edwards RR. Distress Intolerance and Prescription Opioid Misuse Among Patients With Chronic Pain. J Pain. 2016 Jul;17(7):806-14. doi: 10.1016/j.jpain.2016.03.004. Epub 2016 Apr 4. — View Citation

Morean ME, de Wit H, King AC, Sofuoglu M, Rueger SY, O'Malley SS. The drug effects questionnaire: psychometric support across three drug types. Psychopharmacology (Berl). 2013 May;227(1):177-92. doi: 10.1007/s00213-012-2954-z. Epub 2012 Dec 28. — View Citation

Natusch D. Equianalgesic doses of opioids - their use in clinical practice. Br J Pain. 2012 Feb;6(1):43-6. doi: 10.1177/2049463712437628. No abstract available. — View Citation

Naude PJW, Roest AM, Stein DJ, de Jonge P, Doornbos B. Anxiety disorders and CRP in a population cohort study with 54,326 participants: The LifeLines study. World J Biol Psychiatry. 2018 Sep;19(6):461-470. doi: 10.1080/15622975.2018.1433325. Epub 2018 Feb 22. — View Citation

Schaffer CB, Nordahl TE, Schaffer LC, Howe J. Mood-elevating effects of opioid analgesics in patients with bipolar disorder. J Neuropsychiatry Clin Neurosci. 2007 Fall;19(4):449-52. doi: 10.1176/jnp.2007.19.4.449. — View Citation

Sgoifo A, Carnevali L, Alfonso Mde L, Amore M. Autonomic dysfunction and heart rate variability in depression. Stress. 2015;18(3):343-52. doi: 10.3109/10253890.2015.1045868. Epub 2015 May 25. — View Citation

Sneader, W. (2005). Drug discovery : a history. Chichester: Wiley.

Stanley TH. The history and development of the fentanyl series. J Pain Symptom Manage. 1992 Apr;7(3 Suppl):S3-7. doi: 10.1016/0885-3924(92)90047-l. — View Citation

Stone AL, Becker LG, Huber AM, Catalano RF. Review of risk and protective factors of substance use and problem use in emerging adulthood. Addict Behav. 2012 Jul;37(7):747-75. doi: 10.1016/j.addbeh.2012.02.014. Epub 2012 Feb 24. — View Citation

Thomas EA, Garland EL. Mindfulness is Associated With Increased Hedonic Capacity Among Chronic Pain Patients Receiving Extended Opioid Pharmacotherapy. Clin J Pain. 2017 Feb;33(2):166-173. doi: 10.1097/AJP.0000000000000379. — View Citation

Tracey I, Woolf CJ, Andrews NA. Composite Pain Biomarker Signatures for Objective Assessment and Effective Treatment. Neuron. 2019 Mar 6;101(5):783-800. doi: 10.1016/j.neuron.2019.02.019. — View Citation

Wang LP, Hermann C, Westrin P. Thiopentone requirements in adults after varying pre-induction doses of fentanyl. Anaesthesia. 1996 Sep;51(9):831-5. doi: 10.1111/j.1365-2044.1996.tb12611.x. — View Citation

* Note: There are 30 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other Heart rate beats/min prior opioid and post opioid intravenously 10 min
Other Heart rate variability Heart rate variability (HRV) prior opioid and post opioid intravenously 10 min
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
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