NCT05639712

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

Understanding Opioid Use Before and After Surgery in Norway: A Prospective Multicenter Study and Randomized Double-blind Controlled Study

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1,020 (actual)
• Sponsor: Oslo University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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

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

Interventions

Type	Name	Description
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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	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
DRUG	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

Timeline

• Start date: 2022-12-13
• Primary completion: 2025-05-27
• Completion: 2025-06-27
• First posted: 2022-12-06
• Last updated: 2025-09-04

Locations

1 site across 1 country: Norway