Efficacy of Non-opioid Drugs in Addition to Opioid Therapy for Cancer Pain Management

Официальное название

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

Обзор

The investigators investigate the efficacy of non-opioid analgesics compared to placebo together with opioid therapy for cancer pain management.

Подробное описание

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.

Вмешательства

• Препарат Metamizole
  Metamizole 4 g/d as: 2 capsules of 500 mg Metamizole each (1000 mg) taken 4 x daily orally.
• Препарат Ibuprofen
  Ibuprofen 1.2 g/d as: 2 capsules of 150 mg Ibuprofen each (300 mg) taken 4 x daily orally
• Другое Placebo
  Placebo 0 g/d as: 2 capsules containing inactive substance (mannitol) taken 4 x daily orally.

Первичные конечные точки

• Change in cancer pain [Срок оценки: up to 5 days]

Вторичные конечные точки (12)

• Assessment of equivalence of metamizole and ibuprofen in analgesic potency regarding the pain intensity [Срок оценки: up to 5 days]
• Worst pain in the past 24 hours by NRS [Срок оценки: up to 8 days]
• Least pain in the past 24 hours by NRS [Срок оценки: up to 8 days]
• Daily differences in pain intensity measured by NRS [Срок оценки: up to 7 days]
• Patient's Individual Primary Goal (IPG) achieved [Срок оценки: 8 days]
• Personal Symptom Goal (PSG) achieved [Срок оценки: up to 7 days]
• Time to pain control [in days] [Срок оценки: up to 7 days]
• Patient Global Impression of Pain Change (PGIC) by verbal rating scale (VRS) [Срок оценки: day 8]
• ≥30% reduction in daily average pain (Yes/No) [Срок оценки: up to 7 days]
• Burden through interference of pain with general activity by NRS [Срок оценки: up to 8 days]
• Burden through interference of pain with mood by NRS [Срок оценки: up to 8 days]
• Number of opioid rescue medications per day [Срок оценки: up to 8 days]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Швейцария · 1 центр

• University Hospital Basel — Basel

Идентификаторы

NCT: NCT07682558 · 2026-00784; ex23gaertner

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗