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

18 augustus 2026 bijgewerkt door: University Hospital, Basel, Switzerland

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

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

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

318

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verdrievoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Opioid + Metamizole
Geneesmiddel: Metamizole
Metamizole 4 g/d as: 2 capsules of 500 mg Metamizole each (1000 mg) taken 4 x daily orally.
Experimenteel: Opioid + Ibuprofen
Geneesmiddel: Ibuprofen
Ibuprofen 1.2 g/d as: 2 capsules of 150 mg Ibuprofen each (300 mg) taken 4 x daily orally
Placebo-vergelijker: Opioid + Placebo
Ander: Placebo
Placebo 0 g/d as: 2 capsules containing inactive substance (mannitol) taken 4 x daily orally.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in cancer pain
Tijdsspanne: up to 5 days

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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Assessment of equivalence of metamizole and ibuprofen in analgesic potency regarding the pain intensity
Tijdsspanne: up to 5 days
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.
up to 5 days
Time to pain control [in days]
Tijdsspanne: up to 7 days
  1. Time until minimal clinically important difference (MCID) of 1 is achieved
  2. Time until PSG is achieved

MCID and PSG achieved (Yes/No) will be assessed daily from day 3 to 7.
up to 7 days
≥30% reduction in daily average pain (Yes/No)
Tijdsspanne: up to 7 days
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).
up to 7 days
Burden through interference of pain with general activity by NRS
Tijdsspanne: up to 8 days
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.
up to 8 days
Burden through interference of pain with mood by NRS
Tijdsspanne: up to 8 days
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.
up to 8 days
Number of opioid rescue medications per day
Tijdsspanne: up to 8 days
The daily number of IROs (Immediate Release Opioids) will be assessed.
up to 8 days
Number of pain episodes
Tijdsspanne: up to 8 days
This outcome will be assessed at baseline, daily between day 3 and 7. It will also be assessed at EOS.
up to 8 days
Duration [in minutes] of pain episodes
Tijdsspanne: up to 8 days
This outcome will be assessed at baseline, daily between day 3 and 7. It will also be assessed at EOS.
up to 8 days
Worst pain in the past 24 hours by NRS
Tijdsspanne: up to 8 days
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).
up to 8 days
Least pain in the past 24 hours by NRS
Tijdsspanne: up to 8 days
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.
up to 8 days
Daily differences in pain intensity measured by NRS
Tijdsspanne: up to 7 days
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")
up to 7 days
Patient's Individual Primary Goal (IPG) achieved
Tijdsspanne: 8 days

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
Personal Symptom Goal (PSG) achieved
Tijdsspanne: up to 7 days

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
Patient Global Impression of Pain Change (PGIC) by verbal rating scale (VRS)
Tijdsspanne: day 8
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").
day 8
Morphine Equivalent Daily Dose (MEDD) (in mg) calculated by compound, dose and application route of IROs (Immediate Release Opioid) and EROs (Extended-release Opioids)
Tijdsspanne: up to 7 days

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

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of patients with ≥30% reduction in pain
Tijdsspanne: up to 7 days
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)
up to 7 days
Adherence to protocol and IMP intake
Tijdsspanne: up to 7 days

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
Number of participants that opened the capsules
Tijdsspanne: up to 8 days
Administration assessed daily as "Capsules opened: Yes/No".
up to 8 days
Number of participants that received the IMP through an enteral tube
Tijdsspanne: up to 8 days
Assessed daily as "Administration through enteral tube": Yes/No, if "capsules opened: Yes"
up to 8 days
Continuation of non-opioid treatment
Tijdsspanne: up to 8 days
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.
up to 8 days
Differences in treatment response based on CRP (C-reactive protein) status at baseline
Tijdsspanne: Baseline and day 8
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).
Baseline and day 8
Changes in symptoms at EOS compared to baseline
Tijdsspanne: up to 8 days

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
Changes in activity levels at EOS compared to baseline
Tijdsspanne: up to 8 days
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).
up to 8 days
Accuracy of participant treatment guess
Tijdsspanne: up to 8 days
(Correct vs incorrect vs unsure) based on comparison with actual treatment allocation
up to 8 days
Incidence of (serious) adverse events ((S)AEs)
Tijdsspanne: up to 8 days
up to 8 days
Type and duration of (S)AEs
Tijdsspanne: up to 8 days
up to 8 days
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
Tijdsspanne: up to 8 days
up to 8 days
Number of dropouts due to clinically relevant decrease in leukocyte count (≥50% from baseline) attributed to metamizole
Tijdsspanne: up to 8 days
up to 8 days
Changes in performance status (ECOG) at EOS compared to baseline
Tijdsspanne: up to 8 days
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.
up to 8 days

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University Hospital, Basel, Switzerland

Medewerkers

Swiss National Science Foundation
Swiss GO Trial Group

Onderzoekers

  • Hoofdonderzoeker: Christopher Boehlke, Prof. Dr., University Hospital, Basel, Switzerland

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 oktober 2026

Primaire voltooiing (Geschat)

1 november 2029

Studie voltooiing (Geschat)

1 november 2029

Studieregistratiedata

Eerst ingediend

26 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

26 juni 2026

Eerst geplaatst (Werkelijk)

6 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

19 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

18 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2026-00784; ex23gaertner

Plan Individuele Deelnemersgegevens (IPD)

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Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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