Efficacy of Non-opioid Drugs in Addition to Opioid Therapy for Cancer Pain Management (NoDoubt)
Efficacy of Non-opioid Drugs in Addition to Opioid Therapy for Cancer Pain Management: a Double-blind, Randomized, Three Arm, Placebo Controlled Trial Assessing the Key Non-opioids Dipyrone (Metamizole) and Ibuprofen
調査の概要
詳細な説明
Pain in cancer is common and can be very debilitating. Approximately half of all people with a tumor experience moderate to severe pain during the course of patient's cancer. Nevertheless, pain management is often difficult because there are not yet enough reliable studies for some medications, especially when used in addition to opioids.
Therefore, the NoDoubt study is investigating whether metamizole and/or ibuprofen - compared to a placebo - in addition to opioids provide better pain relief for cancer patients. The main goal is to reduce pain intensity. The study also examines whether the need for opioids can be reduced. The results could help to establish a clear and standardized practice for the treatment of cancer pain in the future, thus leading to improved care for cancer patients.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Christopher Boehlke, Prof. Dr.
- 電話番号：+41 61 265 25 25,
- メール：christopher.boehlke@unibas.ch
研究連絡先のバックアップ
- 名前：Ursina Wernli, PhD
- メール：ursina.wernli@usb.ch
研究場所
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Basel、スイス、4031
- University Hospital Basel
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コンタクト：
- Christopher Boehlke, Prof. Dr.
- 電話番号：+41 61 265 25 25
- メール：christopher.boehlke@unibas.ch
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Inpatient setting (discharge possible, if patient returns for End of Study Visit)
- Diagnosis of metastatic or locally advanced cancer
- Cancer pain as defined by IASP (International Association for the Study of Pain)
- Cancer pain therapy with opioids indicated for pain management or start thereof at baseline (drug, dose, and route at treating physician's discretion)
- Average daily pain intensity ≥ 3 on NRS (Numeric Rating Scale)
- Ability to swallow oral medication
- Informed Consent as documented by signature
Exclusion Criteria:
- History of allergy or allergy-like symptoms (bronchospasm, urticaria or severe cutaneous adverse reactions (SCARs)) or hypersensitivity to dipyrone (or other pyrazolones or pyrazolidines) or ibuprofen (or other Non-steroidal anti-inflammatory drug incl. acetylsalicylic acid)
- Moderate to severe renal insufficiency (creatinine-eGFR (estimated Glomerular Filtration Rate) <45 ml/min)
- Severe heart failure (New York Heart Association class III-IV)
- Severe hepatic impairment (liver cirrhosis with ascites) or hepatic porphyria
- History of agranulocytosis induced by dipyrone (or other pyrazolones or pyrazolidines)
- Active gastric and/or duodenal ulcers or bleeding
- History of recurrent gastric and/or duodenal ulcers or gastrointestinal bleeding (≥2 distinct episodes of proven ulceration or bleeding) or increased tendency to bleeding
- Third trimester of pregnancy
- Breastfeeding
- G6PD deficiency
- Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- Intrathecal or epidural opioids or local or regional anesthetic therapy
- Additional second opioid for co-analgesic effects or other reasons (e.g., methadone, buprenorphine)
- Initiation of therapy with transdermal therapeutic system (TTS) opioid <48 hours before start of IMP
- Use of non-opioids with long half-life (i.e., acemetacin, celecoxib, etodolac, etoricoxib, ketorolac, naproxen, piroxicam, tenoxicam)
- Pain unrelated to cancer (e.g. chronic non-cancer pain [CNCP], postoperative, particularly following coronary artery or cardiopulmonary bypass surgery)
- Inability to follow study procedures or adhere to protocol (e.g., due to language problems, psychological disorders, dementia)
- Inability to abstain from other non-opioids (apart from IMP (Investigational Medicinal Product)) during study participation
- Participation in any interventional study targeted at pain management
- Participant is a family member or employee of the investigator
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：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Opioid + Metamizole
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Metamizole 4 g/d as: 2 capsules of 500 mg Metamizole each (1000 mg) taken 4 x daily orally.
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実験的：Opioid + Ibuprofen
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Ibuprofen 1.2 g/d as: 2 capsules of 150 mg Ibuprofen each (300 mg) taken 4 x daily orally
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プラセボコンパレーター：Opioid + Placebo
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Placebo 0 g/d as: 2 capsules containing inactive substance (mannitol) taken 4 x daily orally.
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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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Change in cancer pain
時間枠：up to 5 days
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The primary outcome will help to determine whether adding metamizole (dipyrone) or ibuprofen to opioids is more effective than adding placebo in reducing average daily pain intensity (primary outcome) in cancer patients. - Average of 5-day average daily patient reported pain assessed on days 3 to 7 by numeric rating scale (NRS); The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine") |
up to 5 days
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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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Assessment of equivalence of metamizole and ibuprofen in analgesic potency regarding the pain intensity
時間枠：up to 5 days
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Our main secondary outcome will help to investigate whether metamizole and ibuprofen demonstrate similar analgesic potency (are equivalent) regarding the pain intensity.
For assessment of equivalence, Average of 5-day average daily patient reported pain assessed on days 3 to 7 by numeric rating scale will be used.
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up to 5 days
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Time to pain control [in days]
時間枠：up to 7 days
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MCID and PSG achieved (Yes/No) will be assessed daily from day 3 to 7. |
up to 7 days
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≥30% reduction in daily average pain (Yes/No)
時間枠：up to 7 days
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This outcome will be assessed based on the average of daily patient reported pain intensity by NRS at baseline (BL-pain) compared to the daily average pain on the last day of the intervention period (day 7).
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up to 7 days
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Burden through interference of pain with general activity by NRS
時間枠：up to 8 days
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Will be assessed at baseline and daily from day 3 to 7 using item 9 A ("General activity") of the BPI-SF.
The NRS ranges from 0 ("does not interfere") to 10 ("completely interferes").
Both outcomes will also be assessed at EOS.
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up to 8 days
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Burden through interference of pain with mood by NRS
時間枠：up to 8 days
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Will be assessed at baseline and daily from day 3 to 7 using item 9 B ("Mood") of the BPI-SF.
The NRS ranges from 0 ("does not interfere") to 10 ("completely interferes").
Both outcomes will also be assessed at EOS.
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up to 8 days
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Number of opioid rescue medications per day
時間枠：up to 8 days
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The daily number of IROs (Immediate Release Opioids) will be assessed.
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up to 8 days
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Number of pain episodes
時間枠：up to 8 days
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This outcome will be assessed at baseline, daily between day 3 and 7.
It will also be assessed at EOS.
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up to 8 days
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Duration [in minutes] of pain episodes
時間枠：up to 8 days
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This outcome will be assessed at baseline, daily between day 3 and 7.
It will also be assessed at EOS.
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up to 8 days
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Worst pain in the past 24 hours by NRS
時間枠：up to 8 days
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This outcome will be assessed at baseline and daily from day 3 to 7 using item 3 of the BPI-SF (Brief Pain Inventory - Short Form).
The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine").
It will also be assessed at End of Study Visit (EOS).
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up to 8 days
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Least pain in the past 24 hours by NRS
時間枠：up to 8 days
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This outcome will be assessed at baseline and daily from day 3 to 7 using item 4 of the BPI-SF.
The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine").
It will also be assessed at EOS.
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up to 8 days
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Daily differences in pain intensity measured by NRS
時間枠：up to 7 days
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This outcome will be assessed daily from day 3 to day 7 to investigate efficacy over the course of time.
The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine")
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up to 7 days
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Patient's Individual Primary Goal (IPG) achieved
時間枠：8 days
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The IPG will be specified at baseline and whether it has been achieved or not will be assessed at EOS based on the specified IPG at baseline. The IPG reflects variation between individuals' analgesic goals and further individualize symptom assessment by allowing each patient to specify a primary goal regarding the amelioration of the main issue as asked at baseline (i.e., patient's most important item from this list: average pain, pain interference with mood or activity, number or duration of pain episodes, worst pain, other). |
8 days
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Personal Symptom Goal (PSG) achieved
時間枠：up to 7 days
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The PSG will be specified at baseline (NRS 0-10) and whether it has been achieved or not will be assessed daily from day 3 to 7. Patients are asked at baseline "At what level would you feel comfortable with this symptom?" to identify the maximal symptom intensity they would consider comfortable on the NRS ranging from 0 ("no pain") to 10 ("pain as bad as the patient can imagine"). |
up to 7 days
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Patient Global Impression of Pain Change (PGIC) by verbal rating scale (VRS)
時間枠：day 8
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A 7-option rating-of-change scale to assess participant-reported response to pain therapy using a VRS ("very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse").
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day 8
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Morphine Equivalent Daily Dose (MEDD) (in mg) calculated by compound, dose and application route of IROs (Immediate Release Opioid) and EROs (Extended-release Opioids)
時間枠：up to 7 days
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Baseline MEDD and MEDD at EOS will be assessed. This outcome will be assessed daily between day 1 and 7. MEDD is calculated by multiplying the daily dose of the prescribed opioid (if not already morphine) by a compound-specific, route of application-dependent conversion factor. The opioid conversion ratios used to calculate MEDD are based on the literature and practical clinical considerations on equianalgesic dosing. |
up to 7 days
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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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Number of patients with ≥30% reduction in pain
時間枠：up to 7 days
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For this outcome, the number of patients achieving ≥30% reduction in pain will be assessed, comparing pain at baseline (BL-pain) to the daily average pain on the last day of the intervention (day 7)
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up to 7 days
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Adherence to protocol and IMP intake
時間枠：up to 7 days
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Discharge during d1-d7 will be assessed (Yes/No), including time to discharge after inclusion, if applicable. IMP intake (i.e., missed doses day d1-d7) will be assessed daily. |
up to 7 days
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Number of participants that opened the capsules
時間枠：up to 8 days
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Administration assessed daily as "Capsules opened: Yes/No".
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up to 8 days
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Number of participants that received the IMP through an enteral tube
時間枠：up to 8 days
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Assessed daily as "Administration through enteral tube": Yes/No, if "capsules opened: Yes"
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up to 8 days
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Continuation of non-opioid treatment
時間枠：up to 8 days
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This will be assessed at EOS based on the clinical decision at physician's discretion (after unblinding).
It will be assessed whether the non-opioid is continued, discontinued, switched, or if a (new) non-opioid is initiated.
If applicable, the drug and the daily dose (mg/24 h) will be assessed.
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up to 8 days
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Differences in treatment response based on CRP (C-reactive protein) status at baseline
時間枠：Baseline and day 8
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The CRP measured at baseline will be used to exploratively assess whether treatment response differs according to baseline inflammatory status as measured by CRP (i.e., whether baseline inflammation may act as a potential effect modifier of the observed treatment response).
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Baseline and day 8
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Changes in symptoms at EOS compared to baseline
時間枠：up to 8 days
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Using ESAS (Edmonton Symptom Assessment System): This scale is designed to help assess pain, tiredness, drowsiness, nausea, depression, anxiety, appetite, wellbeing, and shortness of breath. The blank scale can be used to assess "other problems" as needed. Each symptom's severity at the time of assessment is rated from 0 to 10; 0 meaning the symptom is absent and 10 being the worst possible severity. |
up to 8 days
|
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Changes in activity levels at EOS compared to baseline
時間枠：up to 8 days
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Average activity levels of the past 7 days will be assessed at baseline and at EOS using a NRS (numeric rating scale) ranging from 0 (no activity at all) to 10 (maximum possible activity/the same as in health).
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up to 8 days
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Accuracy of participant treatment guess
時間枠：up to 8 days
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(Correct vs incorrect vs unsure) based on comparison with actual treatment allocation
|
up to 8 days
|
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Incidence of (serious) adverse events ((S)AEs)
時間枠：up to 8 days
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up to 8 days
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Type and duration of (S)AEs
時間枠：up to 8 days
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up to 8 days
|
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Number of dropouts due to decrease in creatinine-estimated (e)GFR <30 ml/min and/or ≥1.5-fold increase in baseline serum creatinine attributed to ibuprofen
時間枠：up to 8 days
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up to 8 days
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Number of dropouts due to clinically relevant decrease in leukocyte count (≥50% from baseline) attributed to metamizole
時間枠：up to 8 days
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up to 8 days
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Changes in performance status (ECOG) at EOS compared to baseline
時間枠：up to 8 days
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Using the ECOG (Eastern Cooperative Oncology Group) performance status.
It describes a patient's level of functioning based on the ability to perform self-care, daily activities, and physical activities (e.g., walking and working).
The scale runs from 0 to 5, where lower numbers indicate better functioning.
However, as 5 indicates death, only 0 to 4 are used for assessment of this outcome.
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up to 8 days
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協力者と研究者
捜査官
- 主任研究者：Christopher Boehlke, Prof. Dr.、University Hospital, Basel, Switzerland
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
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
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