Affective effects of pre-surgery opioids (AFFECT2): a randomized, doubleblind placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vestre Viken HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Physiological processes [G07]

Trial duration

13 Dec 2022 → ongoing

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518308-37-00

EudraCT number

2022-002938-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic

The primary purpose of the RCT AFFECT2 is to identify and compare the
different affective states of the participants after the administration of
one of three opioids: morphine, oxycodone or fentanyl, commonly used
in surgery settings before the induction of general anaesthesia at one of
three equianalgesic doses intravenously: 2.5mg, 5mg and 10mg of
morphine. ( Oxycodone : 2.5 mg, 5 mg and 10 mg. Fentanyl : 0,025 mg,
0.05 mg and 0.1 mg). There will also be a placebo group receiving saline
0.9%.

Secondary objectives 1

1. 1. To compare physiological responses between the three different drug groups, specifically change from pre to post drug measurements between groups. 2. To determine the relation between psychological and social risk factors with acute drug effects.

Conditions and MedDRA coding

Health status ASA1 or ASA2 as categorised by a medical doctor at the hospital based on medical history and physical examination. The American Society of Anesthesiologists physical status (ASA1: "Healthy, non-smoking, no or minimal alcohol use" and ASA 2: "Mild diseases only without substantive functional limitations). Being eligible for day surgery means participants are overtly healthy as determined by clinical staff, but also inpatients undergoing surgery who are ASA 1 and 2.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants must be 18 years of age or above at the time of signing the informed consent.
2. Health status ASA1 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. The American Society Anesthesiologists physical status 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. Also inpatients classified as ASA 1 and 2 can be included.
3. 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.
4. Body weight and body mass index (BMI) within the range 18-35 kg/m2 (inclusive).
5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
6. Having good verbal communication skills in Norwegian
7. Patients undergoing planned day surgery with general anaesthesia (outpatient sample): Orthopedic, minor gastrointestinal surgery, gynecological, hand and footsurgery, and minor vascular procedures
8. Inpatients undergoing planned gynecological and orthopedic surgery: hysterectomia, laparascopic ovarectomia, lumbal herniotomy, and other related procedures. Also minor gastrointestinal surgery .

Exclusion criteria 18

1. Known allergic reactions to morphine, oxycodone,or fentanyl.
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. Myastenia 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. Prior or ongoing use of illicit drugs like opioids, cocaine and amphetamine.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. The primary endpoints will be the mean ratings for each drug as follows (rated by the participants on the operating table using a verbal numeric rating scale (NRS 0-10)).
2. Self-report items: - Numeric rating scales (0-10) on affective states ( pre-drug rating): Good, pain,relaxed,anxious
3. After IV drug administration, the patients is asked to indicate when they first feel a drug effect, and the time (seconds post-administration) is recorded along with the patient's description of this effect
4. after a standardized waiting time (2 min)the study personnel ask further questions about the patients' affective state. In the case that no effect has been indicated within the first two minutes, patients are asked if they feel an effect and if so, to describe it. The patient is then asked to report on an NRS 0-10, again how "good", "anxious", "pain", and "relaxed" they feel on a numerical rating scale NRS 0-10. We also measure acute drug effects such as "high", "liking the effect", "disli

Secondary endpoints 2

1. Mean differences on the objective measures pre- and post opioid administration between the different drug groups: -HRV (heartrate variability)
2. Multiple regressions will be fit to the subjective outcome measures (post-opioid) to investigate variability explained by measures at preopioid. Specifically, the predictor value of measures identified as risk factors for problematic opioid use in previous studies (e.g. prior opioid use, SUD and depression) will be assessed on the subjective items below: • Good • Pain • anxious • Relaxed • Drug high • Euphoric • Drug liking

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vestre Viken HF

Sponsor organisation

Vestre Viken HF

Address

Groenland 32

City

Drammen

Postcode

3045

Country

Norway

Scientific contact point

Organisation

Vestre Viken HF

Contact name

Gernot Ernst

Public contact point

Organisation

Vestre Viken HF

Contact name

Gernot Ernst

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications