手術前のオピオイドの影響：無作為二重盲検プラセボ対照試験 (AFFECT2)
ノルウェーにおける手術前後のオピオイド使用の理解: 前向き多施設研究および無作為化二重盲検対照研究
- 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
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
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Oslo
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Oslo、Oslo、ノルウェー
- Harald Lenz
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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:
- 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.
- 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：他の
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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プラセボコンパレーター：Placebo
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 |
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
他の名前：
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アクティブコンパレータ：Morphine 2.5 mg
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 |
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
他の名前：
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アクティブコンパレータ：Morphine 5 mg
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 |
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
他の名前：
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アクティブコンパレータ：Morphine 10 mg
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 |
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
他の名前：
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アクティブコンパレータ：Oxycodone 2.5 mg
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 |
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
他の名前：
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アクティブコンパレータ：Oxycodone 5 mg
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 |
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
他の名前：
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アクティブコンパレータ：Oxycodone 10 mg
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 |
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
他の名前：
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アクティブコンパレータ：Fentanyl 0.025 mg
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 |
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
他の名前：
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アクティブコンパレータ：Fentanyl 0.05 mg
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 |
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
他の名前：
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アクティブコンパレータ：Fentanyl 0.1 mg
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 |
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
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Anxious
時間枠：8-10 minutes
|
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
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Relaxed
時間枠：8-10 minutes
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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
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Pain level
時間枠：8-10 minutes
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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
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Good
時間枠：8-10 minutes
|
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
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Dizzy
時間枠：2-4 minutes
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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
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Sedated
時間枠：2-4 minutes
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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
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Feeling high, Numeric rating scale 0 -10
時間枠：2-4 minutes
|
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
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Euphoric
時間枠：2-4 minutes
|
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
|
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Drug liking
時間枠：2-4 minutes
|
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
|
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Drug disliking
時間枠：2-4 minutes
|
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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Onset time
時間枠：Subjective onset time of the three opioids during the 2 minutes observation time before anaesthesia induction
|
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 |
Subjective onset time of the three opioids during the 2 minutes observation time before anaesthesia induction
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Heart rate
時間枠：10 min
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beats/min prior opioid and post opioid intravenously |
10 min
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Heart rate variability
時間枠：10 min
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Heart rate variability (HRV) prior opioid and post opioid intravenously |
10 min
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Gernot Ernst, MD,PhD、Kongsberg Hospital, Vestre Viken Health Trust Norway
出版物と役立つリンク
一般刊行物
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研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- AFFECT2 Version 2, 04.11.2022
- 2022-002938-13 (EudraCT番号)
- 2024-518308-37-00 (Ctis)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
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